Scott Sutherland

All Publications

• Fluid accumulation and outcomes in children receiving continuous kidney replacement therapy: an appraisal of the WE-ROCK registry. Pediatric nephrology (Berlin, Germany) Selewski, D. T., Gist, K. M., Deep, A., Elbahlawan, L., Fuhrman, D. Y., Gelbart, B., Gorga, S. M., Mah, K. E., Ollberding, N. J., Reynaud, S., Seo, J., Soranno, D. E., Stanski, N. L., Starr, M. C., Uber, A. M., Askenazi, D. J., Sutherland, S. M., Menon, S. 2026

  Abstract

  The prospective pediatric Continuous Renal Replacement Therapy (ppCRRT) registry identified the degree of fluid accumulation (FA) at continuous kidney replacement therapy (CKRT) initiation as a predictor of adverse outcomes in children. These predate major advancements in CKRT technology and fluid stewardship. We aimed to describe the epidemiology of FA at CKRT initiation and associated outcomes in a contemporary paediatric cohort.Secondary analysis of Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK), a retrospective, multicenter study (35 centers, 9 countries) of patients ≤ 25 years treated with CKRT from 2015 to 2021.survival to ICU discharge.ventilator-free and ICU-free days.A total of 1027 patients were included in this analysis. Survival to ICU discharge was 64.5% (n = 663). Median FA at CKRT initiation was 7.4% (IQR 2.4-18.1). FA differed between ICU survivors and non-survivors (7% [IQR 2-17] vs. 9% [IQR 3-21], p = 0.004). At CKRT initiation, 605 patients (58.9%) had FA < 10%, 194 patients (18.9%) had 10%-20% FA, and 228 patients (22.2%) had > 20% FA. In multivariable analysis, FA at CKRT initiation was not associated with ICU mortality but was associated with fewer ventilator (aOR 0.84, 95%CI 0.76-0.94, p = 0.023) and ICU-free days (aOR 0.6, 95%CI 0.49-0.73, p < 0.001).The current study provides a contemporary evaluation of the epidemiology and impact of FA at CKRT initiation on outcomes in a cohort of > 1000 children treated with CKRT for FA/AKI. Clinically significant FA remains common at CKRT initiation and is associated with outcomes. This contemporary data can be used to inform clinical care and plan prospective studies.

  View details for DOI 10.1007/s00467-026-07308-4

  View details for PubMedID 42049965

  View details for PubMedCentralID 7517652

• Nutrition delivery in infants with kidney failure on extracorporeal kidney replacement therapy. Pediatric nephrology (Berlin, Germany) Krieger, S. L., Zhou, M. S., Popovich, L., Wong, C., Davis, A. S., Sutherland, S. M., Menon, S. 2026

  Abstract

  Infants with kidney failure who initiate kidney replacement therapy (KRT) within 3 months of life require optimal fluid and nutritional management to support growth. Continuous or prolonged intermittent KRT (CKRT or PIKRT) is often used as a bridge to peritoneal dialysis facilitating earlier nutrition provision but is associated with protein losses. Current guidelines recommend ≥ 3-3.5 g/kg/day of protein during KRT. We aimed to assess nutritional prescriptions and growth in these infants.We conducted a retrospective review of infants with kidney failure managed with extracorporeal KRT at Lucile Packard Children's Hospital between January 2021 and December 2024. Demographics, dialysis dose, nutrition prescriptions, anthropometry, and laboratory values were collected weekly from birth through 8 weeks and at discharge.Seventeen infants were included; 12 (71%) were female. KRT was initiated at a median age of 3 days and a median weight of 2110 g. Initial modality was PIKRT in 15 (88%) and CKRT in 2 (12%). The median prescribed protein was 2.7 g/kg/day in Week 1, increasing to 4 g/kg/day by Week 6. Caloric prescriptions rose from 95 kcal/kg/day in Week 1 to 136 kcal/kg/day by Week 8. Median z-scores for weight, length, and head circumference decreased from birth to Week 8 (weight - 1.07 to - 1.34; length - 1.02 to - 1.95; head circumference - 0.41 to - 1.36), with discharge values of - 1.08, - 1.73, and - 1.40.Despite early KRT and nutritional optimization, infants showed limited catch-up growth. Early provision of ≥ 4 g/kg/day protein and ≥ 130 kcal/kg/day may prevent cumulative deficits.

  View details for DOI 10.1007/s00467-026-07236-3

  View details for PubMedID 41764143

  View details for PubMedCentralID 12549734

• Trends in End-Stage Kidney Disease Due to Reflux Nephropathy in Children and Young Adults. Pediatrics Wolf, A. J., Liu, S., Stedman, M., Grimm, P., Chaudhuri, A., Hains, D. S., Starr, M. C., Kan, K., Sutherland, S. M., Schroeder, A. R. 2026

  Abstract

  Up to 50% of children with urinary tract infections (UTIs) have vesicoureteral reflux (VUR). Severe VUR can lead to reflux nephropathy (RN) and end-stage kidney disease (ESKD). In 2011, the American Academy of Pediatrics UTI guidelines suggested selective voiding cystourethrogram (VCUG), departing from previous recommendations to obtain VCUG after all febrile UTIs in children aged less than 2 years. It is unknown whether the subsequent decrease in VCUG has led to increased preventable kidney damage. This study's objective is to evaluate recent trends in the US incidence of pediatric ESKD owing to RN.This retrospective cohort study used the US Renal Data System, a database that includes all US patients with ESKD. We identified patients aged 24 years and younger with ESKD attributed to RN from 2002 to 2021 as well as diagnoses that may overlap with RN. We used the US Census Bureau data to ascertain population incidence and a Poisson regression model for average annual percentage change (AAPC).There were 46 000 cases of ESKD. The all-cause incidence of ESKD decreased (AAPC of -1.0%; 95% CI, -1.4% to -0.7%) as did the incidence of ESKD owing to RN (AAPC of -4.4%; 95% CI, -5.8% to -3.0%). The incidence of ESKD from obstructive uropathies and renal dysplasia also decreased; however, the incidence of other nonspecific congenital anomalies of the kidney and urinary tract increased.The declining use of VCUG over the last decade has not resulted in a measurable worsening of ESKD related to identified RN at the population level. Continued surveillance over time and investigations into shorter-term kidney outcomes are needed.

  View details for DOI 10.1542/peds.2025-072092

  View details for PubMedID 41582309

• A multi-center collaborative highlights the differences in nephrotoxic medication exposure and associated AKI in pediatric bone marrow transplant, oncology, and pulmonary service lines PEDIATRIC NEPHROLOGY Steinke, J. M., Gist, K. M., Askenazi, D., Ogden, R. K., Shin, S., Sutherland, S., Yonekawa, K., Mahon, A., Fadrowski, J., Misurac, J., Semanik, M., Goldstein, S. L. 2025

  Abstract

  Nephrotoxic medication (NTMx) exposure is a common cause of hospital-acquired acute kidney injury (AKI) in non-critically ill, hospitalized children. NINJA (Nephrotoxic Injury Negated by Just-In-Time Action), an AKI screening and quality improvement tool, has successfully decreased exposure to NTMx and associated AKI at various US children's hospitals. We explored NTMx exposure and AKI rates by admitting service to understand patient risk profiles further.AKI screening was performed by daily serum creatinine when high NTMx exposure criteria were met (≥ 3 NTMx or ≥ 3 days of intravenous aminoglycosides or vancomycin). Centers separately reported data from children admitted to hematology-oncology (heme), bone marrow transplant (BMT), and pulmonary services over 5 years (n = 11, 2016-2021). Rates for NTMx exposure and AKI were expressed as events per 1000 patient days. AKI intensity (#AKI days/100 exposure days) was assessed. Adherence to recommended serum creatinine monitoring was a surrogate for AKI event reliability (observed/expected × 100).Mean exposure rates were highest in BMT (26.92), then pulmonary (22.73), and heme (13.01). AKI rates were highest in BMT (6.27), then pulmonary (4.24), and heme (1.82). Heme and BMT had the highest AKI intensity (12.93 and 12.25 AKI days per 100 high-NTMx exposure days, respectively) compared to pulmonary (7.50 AKI days/100 high-NTMx exposure days). Serum creatinine monitoring compliance varied between institutions (62.5-100%).Nephrotoxic exposure and AKI rates vary by patient population, with BMT patients having the highest NTMx exposure, AKI rates, and AKI intensity. These findings suggest that sub-populations have different levels of exposure and may require different strategies to reduce the burden of nephrotoxic medications.

  View details for DOI 10.1007/s00467-025-06989-7

  View details for Web of Science ID 001611673200001

  View details for PubMedID 41217467

  View details for PubMedCentralID 3219018

• The Modified Schwartz Equation Overestimates GFR Relative to Cystatin-C in Children Hospitalized with Heart Failure Kalia, M., Chughtai, Z., Dykes, J., Profita, E., Rosenthal, D., Sutherland, S., Nishiguchi, J., Yokota, R., Harber, A., Fasbinder, A., Almond, C. S. ELSEVIER SCIENCE INC. 2025

  View details for Web of Science ID 001548881600092

• Growth after pediatric and neonatal acute kidney injury: a meta-analysis. Pediatric nephrology (Berlin, Germany) Starr, M. C., Patel, M., Zafar, F., Zhou, M. S., Griffin, R., Biruete, A., Cockovski, V., Gbadegesin, R., Fuhrman, D. Y., Gist, K. M., Mammen, C., Menon, S., Morgan, C., Slagle, C. L., Sutherland, S., Zappitelli, M., Soranno, D. E. 2025

  Abstract

  Acute kidney injury (AKI) occurs commonly in critically ill children. The impact of AKI on pediatric growth outcomes has been sparsely described.To compare growth in children with a history of AKI compared to those without AKI. We hypothesized that children with AKI would have worse growth compared to those without AKI.A convenience sample of existing prospective and retrospective cohorts of children with AKI who had already collected or were able to collect data on growth parameters before and after an episode of AKI.There are < 5 studies in the published literature on growth in children with AKI. These investigators were contacted, and additional studies were added by contacting primary investigators of studies of childhood AKI in which data on growth parameters was able to be collected.Children from existing cohorts evaluating AKI (exposure) during childhood. Each included cohort had previously received local IRB approval per institutional guidelines. As our study was a meta-analysis and only used cohort-level data, no IRB approval was required for this report.Growth parameters (length and weight z-scores) before and after an episode of AKI were compared using a meta-means analysis. MOOSE guidelines were used. Data were pooled using a random-effects model. Hedges g was calculated, and Higgins I2 statistic was used to define variability due to between-cohort heterogeneity.We included 3,586 children from 17 existing cohorts of AKI in various populations, including infants, children with cardiac disease, solid organ transplant and critically ill children without cardiac disease with follow-up from 12 months to 11 years after AKI. At most distant follow-up, those with AKI had lower length z-score than those without AKI (mean difference -0.37 [95%CI -0.52, -0.22, p < 0.001]) and lower weight z-score (mean difference of -0.29 [95%CI -0.43, -0.15, p < 0.001]). This difference was most striking in infants, as those with AKI had impaired growth (both length z-score and weight z-score) after AKI compared to those without AKI.The analysis included only a convenience sample of observational cohorts of children, study selection could have been biased, and we did not evaluate the relationship between decreased kidney function (e.g., chronic kidney disease) after AKI in these cohorts and its relationship to poor growth.This meta-analysis found that children with AKI have impaired growth after AKI. These findings were most striking in infants. We suggest focusing on growth outcomes in both clinical care and research investigating the impacts of AKI.NA.

  View details for DOI 10.1007/s00467-025-06801-6

  View details for PubMedID 40343489

  View details for PubMedCentralID 8093091

• Time-course analysis of cisplatin induced AKI in preclinical models: implications for testing different sources of MSCs. Journal of translational medicine Ganguly, A., Chetty, S., Primavera, R., Levitte, S., Regmi, S., Dulken, B. W., Sutherland, S. M., Angeles, W., Wang, J., Thakor, A. S. 2024; 22 (1): 789

  Abstract

  Kidneys are at risk from drug-induced toxicity, with a significant proportion of acute kidney injury (AKI) linked to medications, particularly cisplatin. Existing cytoprotective drugs for cisplatin-AKI carry side effects, prompting a search for better biological therapies. Mesenchymal Stem Cells (MSCs) are under consideration given their regenerative properties, yet their clinical application has not achieved their full potential, mainly due to variability in the source of MSC tested. In addition, translating treatments from rodent models to humans remains challenging due to a lack of standardized dosing and understanding potential differential responses to cisplatin between animal strains.In the current study, we performed a time-course analysis of the effect of cisplatin across different mouse strains and evaluated gender related differences to create a robust preclinical model that could then be used to explore the therapeutic efficacy of different sources of MSCs for their ability to reverse AKI.Our data indicated that different mouse strains produce differential responses to the same cisplatin dosing regimen. Despite this, we did not observe any gender-related bias towards cisplatin nephrotoxicity. Furthermore, our time-course analysis identified that cisplatin-induced inflammation was driven by a strong CXCL1 response, which was used as a putative biomarker to evaluate the comparative therapeutic efficacy of different MSC sources in reversing AKI. Our data indicates that UC-MSCs have a stronger anti-inflammatory effect compared to BM-MSCs and AD-MSCs, which helped to ameliorate cisplatin-AKI.Overall, our data underscores the importance of using an optimized preclinical model of cisplatin-AKI to test different therapies. We identified CXCL1 as a potential biomarker of cisplatin-AKI and identified the superior efficacy of UC-MSCs in mitigating cisplatin-AKI.

  View details for DOI 10.1186/s12967-024-05439-6

  View details for PubMedID 39192240

  View details for PubMedCentralID 4146684

• Pediatric acute kidney injury and adverse health outcomes: using a foundational framework to evaluate a causal link. Pediatric nephrology (Berlin, Germany) Morgan, C., Forest, E., Ulrich, E., Sutherland, S. 2024

  Abstract

  Acute kidney injury (AKI) is a major global health problem, expensive to manage, and its associations with negative pediatric health outcomes have been clearly demonstrated. One of the most fundamental questions to consider as we use previous epidemiological information to advance research and care paradigms is the strength of the causal link between pediatric AKI and health outcomes. In this review, we apply the foundational framework of the Bradford Hill criteria to evaluate the extent to which a causal link exists between AKI and the associated adverse outcomes in children. Available data in children support a causal link between AKI and short-term outcomes including mortality, length of stay, and ventilation time. Clarifying the causal nature of longer term associations requires further high-quality observational studies in children, careful consideration of what defines the most meaningful and measurable longer term outcomes after pediatric AKI, and integration of evolving biological data related to mechanisms of disease. Preventing or mitigating AKI should lead to improved outcomes. Demonstrating such reversibility will solidify confidence in the causal relationship, improve child health, and highlight an aspect which is highly relevant to clinicians, scientists, and policy makers.

  View details for DOI 10.1007/s00467-024-06437-y

  View details for PubMedID 38951220

  View details for PubMedCentralID 5933049

• Intraoperative and Postoperative Hemodynamic Predictors of Acute Kidney Injury in Pediatric Heart Transplant Recipients. Journal of pediatric intensive care Hollander, S. A., Chung, S., Reddy, S., Zook, N., Yang, J., Vella, T., Navaratnam, M., Price, E., Sutherland, S. M., Algaze, C. A. 2024; 13 (1): 37-45

  Abstract

  Acute kidney injury (AKI) is common after pediatric heart transplantation (HT) and is associated with inferior patient outcomes. Hemodynamic risk factors for pediatric heart transplant recipients who experience AKI are not well described. We performed a retrospective review of 99 pediatric heart transplant patients at Lucile Packard Children's Hospital Stanford from January 1, 2015, to December 31, 2019, in which clinical and demographic characteristics, intraoperative perfusion data, and hemodynamic measurements in the first 48 postoperative hours were analyzed as risk factors for severe AKI (Kidney Disease: Improving Global Outcomes [KDIGO] stage ≥ 2). Univariate analysis was conducted using Fisher's exact test, Chi-square test, and the Wilcoxon rank-sum test, as appropriate. Multivariable analysis was conducted using logistic regression. Thirty-five patients (35%) experienced severe AKI which was associated with lower intraoperative cardiac index ( p  = 0.001), higher hematocrit ( p  < 0.001), lower body temperature ( p  < 0.001), lower renal near-infrared spectroscopy ( p  = 0.001), lower postoperative mean arterial blood pressure (MAP: p  = 0.001), and higher central venous pressure (CVP; p  < 0.001). In multivariable analysis, postoperative CVP >12 mm Hg (odds ratio [OR] = 4.27; 95% confidence interval [CI]: 1.48-12.3, p  = 0.007) and MAP <65 mm Hg (OR = 4.9; 95% CI: 1.07-22.5, p  = 0.04) were associated with early severe AKI. Children with severe AKI experienced longer ventilator, intensive care, and posttransplant hospital days and inferior survival ( p  = 0.01). Lower MAP and higher CVP are associated with severe AKI in pediatric HT recipients. Patients, who experienced AKI, experienced increased intensive care unit (ICU) morbidity and inferior survival. These data may guide the development of perioperative renal protective management strategies to reduce AKI incidence and improve patient outcomes.

  View details for DOI 10.1055/s-0041-1736336

  View details for PubMedID 38571984

  View details for PubMedCentralID PMC10987224

• Acute kidney injury in neonates with hypoxic ischemic encephalopathy based on serum creatinine decline compared to KDIGO criteria. Pediatric nephrology (Berlin, Germany) Ahn, H. C., Frymoyer, A., Boothroyd, D. B., Bonifacio, S., Sutherland, S. M., Chock, V. Y. 2024

  Abstract

  Neonates with hypoxic ischemic encephalopathy receiving therapeutic hypothermia (HIE + TH) are at risk for acute kidney injury (AKI). The standardized Kidney Disease Improving Global Outcomes (KDIGO) criteria identifies AKI based on a rise in serum creatinine (SCr) or reduced urine output. This definition is challenging to apply in neonates given the physiologic decline in SCr during the first week of life. Gupta et al. proposed alternative neonatal criteria centered on rate of SCr decline. This study aimed to compare the rate of AKI based on KDIGO and Gupta in neonates with HIE and to examine associations with mortality and morbidity.A retrospective review was performed of neonates with moderate to severe HIE + TH from 2008 to 2020 at a single center. AKI was assessed in the first 7 days after birth by KDIGO and Gupta criteria. Mortality, brain MRI severity of injury, length of stay, and duration of respiratory support were compared between AKI groups.Among 225 neonates, 64 (28%) met KDIGO, 69 (31%) neonates met Gupta but not KDIGO, and 92 (41%) did not meet either definition. Both KDIGO-AKI and GuptaOnly-AKI groups had an increased risk of the composite mortality and/or moderate/severe brain MRI injury along with longer length of stay and prolonged duration of respiratory support compared to those without AKI.AKI in neonates with HIE + TH was common and varied by definition. The Gupta definition based on rate of SCr decline identified additional neonates not captured by KDIGO criteria who are at increased risk for adverse outcomes. Incorporating the rate of SCr decline into the neonatal AKI definition may increase identification of clinically relevant kidney injury in neonates with HIE + TH.

  View details for DOI 10.1007/s00467-024-06287-8

  View details for PubMedID 38326648

  View details for PubMedCentralID 4209658

• Prospective Study of the Multisite Spread of a Medication Safety Intervention: Factors Common to Hospitals With Improved Outcomes. American journal of medical quality : the official journal of the American College of Medical Quality Kaplan, H. C., Goldstein, S. L., Rubinson, C., Daraiseh, N., Zhang, F., Rodgers, I. M., Dahale, D. S., Askenazi, D. J., Somers, M. J., Zaritsky, J. J., Misurac, J., Chadha, V., Yonekawa, K. E., Sutherland, S. M., Weng, P. L., Walsh, K. E. 2023

  Abstract

  Context and implementation approaches can impede the spread of patient safety interventions. The objective of this article is to characterize factors associated with improved outcomes among 9 hospitals implementing a medication safety intervention. Nephrotoxic Injury Negated by Just-in-Time Action (NINJA) is a pharmacist-driven intervention that led to a sustained reduction in nephrotoxic medication-associated acute kidney injury (NTMx-AKI) at 1 hospital. Using qualitative comparative analysis, the team prospectively assessed the association between context and implementation factors and NTMx-AKI reduction during NINJA spread to 9 hospitals. Five hospitals reduced NTMx-AKI. These 5 had either (1) a pharmacist champion and >2 pharmacists working on NINJA (Scon 1.0, Scov 0.8) or (2) a nephrologist-implementing NINJA with minimal competing organizational priorities (Scon 1.0, Scov 0.2). Interviews identified ways NINJA team leaders obtained pharmacist support or successfully implemented without that support. In conclusion, these findings have implications for future spread of NINJA and suggest an approach to study spread of safety interventions more broadly.

  View details for DOI 10.1097/JMQ.0000000000000161

  View details for PubMedID 38127682

• Long-term kidney outcomes in pediatric continuous-flow ventricular assist device patients. Pediatric nephrology (Berlin, Germany) Idrovo, A., Hollander, S. A., Neumayr, T. M., Bell, C., Munoz, G., Choudhry, S., Price, J., Adachi, I., Srivaths, P., Sutherland, S., Akcan-Arikan, A. 2023

  Abstract

  BACKGROUND: Continuous-flow ventricular assist devices (CF-VADs) are used increasingly in pediatric end-stage heart failure (ESHF) patients. Alongside common risk factors like oxidant injury from hemolysis, non-pulsatile flow constitutes a unique circulatory stress on kidneys. Post-implantation recovery after acute kidney injury (AKI) is commonly reported, but long-term kidney outcomes or factors implicated in the evolution of chronic kidney disease (CKD) with prolonged CF-VAD support are unknown.METHODS: We studied ESHF patients supported>90days on CF-VAD from 2008 to 2018. The primary outcome was CKD (per Kidney Disease Improving Global Outcomes (KDIGO) criteria). Secondary outcomes included AKI incidence post-implantation and CKD evolution in the 6-12months of CF-VAD support.RESULTS: We enrolled 134 patients; 84/134 (63%) were male, median age was 13 [IQR 9.9, 15.9] years, 72/134 (54%) had preexisting CKD at implantation, and 85/134 (63%) had AKI. At 3months, of the 91/134 (68%) still on a CF-VAD, 34/91 (37%) never had CKD, 13/91 (14%) developed de novo CKD, while CKD persisted or worsened in 49% (44/91). Etiology of heart failure, extracorporeal membrane oxygenation use, duration of CF-VAD, AKI history, and kidney replacement therapy were not associated with different CKD outcomes. Mortality was higher in those with AKI or preexisting CKD.CONCLUSIONS: In the first multicenter study to focus on kidney outcomes for pediatric long-term CF-VAD patients, preimplantation CKD and peri-implantation AKI were common. Both de novo CKD and worsening CKD can happen on prolonged CF-VAD support. Proactive kidney function monitoring and targeted follow-up are important to optimize outcomes. A higher resolution version of the Graphical abstract is available as Supplementary information.

  View details for DOI 10.1007/s00467-023-06190-8

  View details for PubMedID 37971519

• Epidemiology of acute kidney injury in children: a report from the 26th Acute Disease Quality Initiative (ADQI) consensus conference. Pediatric nephrology (Berlin, Germany) Sutherland, S. M., Alobaidi, R., Gorga, S. M., Iyengar, A., Morgan, C., Heydari, E., Arikan, A. A., Basu, R. K., Goldstein, S. L., Zappitelli, M. 2023

  Abstract

  The nephrology and critical care communities have seen an increase in studies exploring acute kidney injury (AKI) epidemiology in children. As a result, we now know that AKI is highly prevalent in critically ill neonates, children, and young adults. Furthermore, children who develop AKI experience greater morbidity and higher mortality. Yet knowledge gaps still exist that suggest a more comprehensive understanding of AKI will form the foundation for future efforts designed to improve outcomes. In particular, the areas of community acquired AKI, AKI in non-critically ill children, and cohorts from low-middle income countries have not been well studied. Longer-term functional outcomes and patient-centric metrics including social determinants of health, quality of life, and healthcare utilization should be the foci of the next phase of scholarship. Current definitions identify AKI-based upon evidence of dysfunction which serves as a proxy for injury; biomarkers capable of identifying injury as it occurs are likely to more accurately define populations with AKI. Despite the strength of the association, the causal and mechanistic relationships between AKI and poorer outcomes remain inadequately examined. A more robust understanding of the relationship represents a potential to identify therapeutic targets. Once established, a more comprehensive understanding of AKI epidemiology in children will allow investigation of preventive, therapeutic, and quality improvement interventions more effectively.

  View details for DOI 10.1007/s00467-023-06164-w

  View details for PubMedID 37874357

  View details for PubMedCentralID 9756303

• Advances in pediatric acute kidney injury pathobiology: a report from the 26th Acute Disease Quality Initiative (ADQI) conference. Pediatric nephrology (Berlin, Germany) Starr, M. C., Barreto, E., Charlton, J., Vega, M., Brophy, P. D., Ray Bignall, O. N., Sutherland, S. M., Menon, S., Devarajan, P., Akcan Arikan, A., Basu, R., Goldstein, S., Soranno, D. E. 2023

  Abstract

  In the past decade, there have been substantial advances in our understanding of the pathobiology of pediatric acute kidney injury (AKI). In particular, animal models and studies focused on the relationship between kidney development, nephron number, and kidney health have identified a number of heterogeneous pathophysiologies underlying AKI. Despite this progress, gaps remain in our understanding of the pathobiology of pediatric AKI.During the 26th Acute Disease Quality Initiative (ADQI) Consensus conference, a multidisciplinary group of experts discussed the evidence and used a modified Delphi process to achieve consensus on recommendations for opportunities to advance translational research in pediatric AKI. The current state of research understanding as well as gaps and opportunities for advancement in research was discussed, and recommendations were summarized.Consensus was reached that to improve translational pediatric AKI advancements, diverse teams spanning pre-clinical to epidemiological scientists must work in concert together and that results must be shared with the community we serve with patient involvement. Public and private research support and meaningful partnerships with adult research efforts are required. Particular focus is warranted to investigate the pediatric nuances of AKI, including the effect of development as a biological variable on AKI incidence, severity, and outcomes.Although AKI is common and associated with significant morbidity, the biologic basis of the disease spectrum throughout varying nephron developmental stages remains poorly understood. An incomplete understanding of factors contributing to kidney health, the diverse pathobiologies underlying AKI in children, and the historically siloed approach to research limit advances in the field. The recommendations outlined herein identify gaps and outline a strategic approach to advance the field of pediatric AKI via multidisciplinary translational research.

  View details for DOI 10.1007/s00467-023-06154-y

  View details for PubMedID 37792076

  View details for PubMedCentralID 9756303

• Advances in pediatric acute kidney injury pathobiology: a report from the 26th Acute Disease Quality Initiative (ADQI) conference PEDIATRIC NEPHROLOGY Starr, M. C., Barreto, E., Charlton, J., Vega, M., Brophy, P. D., Bignall II, O., Sutherland, S. M., Menon, S., Devarajan, P., Arikan, A., Basu, R., Goldstein, S., Soranno, D. E., ADQI 26 Workgrp 2023

  View details for DOI 10.1007/s00467-023-06154

  View details for Web of Science ID 001078763100002

• Digital health and acute kidney injury: consensus report of the 27th Acute Disease Quality Initiative workgroup. Nature reviews. Nephrology Kashani, K. B., Awdishu, L., Bagshaw, S. M., Barreto, E. F., Claure-Del Granado, R., Evans, B. J., Forni, L. G., Ghosh, E., Goldstein, S. L., Kane-Gill, S. L., Koola, J., Koyner, J. L., Liu, M., Murugan, R., Nadkarni, G. N., Neyra, J. A., Ninan, J., Ostermann, M., Pannu, N., Rashidi, P., Ronco, C., Rosner, M. H., Selby, N. M., Shickel, B., Singh, K., Soranno, D. E., Sutherland, S. M., Bihorac, A., Mehta, R. L. 2023

  Abstract

  Acute kidney injury (AKI), which is a common complication of acute illnesses, affects the health of individuals in community, acute care and post-acute care settings. Although the recognition, prevention and management of AKI has advanced over the past decades, its incidence and related morbidity, mortality and health care burden remain overwhelming. The rapid growth of digital technologies has provided a new platform to improve patient care, and reports show demonstrable benefits in care processes and, in some instances, in patient outcomes. However, despite great progress, the potential benefits of using digital technology to manage AKI has not yet been fully explored or implemented in clinical practice. Digital health studies in AKI have shown variable evidence of benefits, and the digital divide means that access to digital technologies is not equitable. Upstream research and development costs, limited stakeholder participation and acceptance, and poor scalability of digital health solutions have hindered their widespread implementation and use. Here, we provide recommendations from the Acute Disease Quality Initiative consensus meeting, which involved experts in adult and paediatric nephrology, critical care, pharmacy and data science, at which the use of digital health for risk prediction, prevention, identification and management of AKI and its consequences was discussed.

  View details for DOI 10.1038/s41581-023-00744-7

  View details for PubMedID 37580570

• A novel acute kidney injury scoring system for renal and clinical outcomes in pediatric heart transplant patients. Pediatric transplantation Mai, D. H., Sutherland, S., Blinder, J., Hollander, S. A. 2023: e14565

  Abstract

  BACKGROUND: The development of acute kidney injury (AKI) has been associated with worse outcomes in children after heart transplantation. Our study compares the application of a cumulative six-point Kidney Diseases Improving Global Outcomes (KDIGO) AKI scoring system, utilizing both creatinine and urine output criteria that we term as the AKI-6 criteria, to traditional AKI staging as a predictor for clinical and renal outcomes in the pediatric heart transplant recipients.METHODS: We conducted a retrospective single-center chart review on 155 pediatric patients who underwent heart transplantation from May 2014 to December 2021. The primary independent variable was the presence of severe AKI. Severe AKI by KDIGO was defined as Stage ≥2, whereas severe AKI by AKI-6 was defined as cumulative scores ≥4 or Stage 3 AKI based on either KDIGO criterion alone. Primary outcomes included actuarial survival and renal dysfunction by 1-year post-transplant, defined as an estimated glomerular filtration rate <60mL/min/1.73m2 .RESULTS: In total, 140 (90%) patients developed AKI; 98 (63%) patients developed severe AKI by KDIGO, and 60 (39%) by AKI-6. Severe AKI by AKI-6 was associated with worse actuarial survival following heart transplantation compared with KDIGO (p=0.01). Of the 143 patients with 1-year creatinine data, 6 (11%) patients out of 54 with severe AKI by AKI-6 had evidence of renal dysfunction (p=0.01), compared with 6 (7%) patients out of 88 by KDIGO (p=0.3).CONCLUSIONS: AKI-6 scoring provides greater prognostic utility for actuarial survival and renal dysfunction by 1-year post-heart transplantation in pediatric patients than traditional KDIGO staging.

  View details for DOI 10.1111/petr.14565

  View details for PubMedID 37409513

• Chronic Implications of an Acute Disease: Long-Term Outcomes in Pediatric Acute Kidney Injury Survivors JOURNAL OF PEDIATRICS Sutherland, S. M. 2023; 255: 7-8

  View details for DOI 10.1018/j.jpeds.2022.10.017

  View details for Web of Science ID 000985463100001

• Clinical Predictive Tool for Pediatric Cardiac Patients on Extracorporeal Membrane Oxygenation Therapy and Ultrafiltration. ASAIO journal (American Society for Artificial Internal Organs : 1992) Sedler, J., Sutherland, S. M., Uber, A. M., Jahadi, O., Ryan, K. R., Yarlagadda, V. V., Kwiatkowski, D. M. 2023

  Abstract

  Fluid overload is common among pediatric cardiac patients receiving extracorporeal membrane oxygenation (ECMO) and is often treated with in-line ultrafiltration (UF) or continuous renal replacement therapy (CRRT). We assessed whether CRRT was associated with poor outcomes versus UF alone. Additionally, we identified characteristics associated with progression from UF to CRRT. Retrospective chart review of 131 patients age ≤18 years treated with ECMO at a single quaternary center. Data were collected to compare patient demographics, characteristics, and outcomes. A receiver operator curve (ROC) was used to create a tool predictive of the need for CRRT at the time of UF initiation. Patients who required CRRT had a higher creatinine and blood urea nitrogen at time of UF initiation (p = 0.03 and p < 0.01), longer total ECMO duration (p < 0.01), lower renal recovery incidence (p = 0.02), and higher mortality (p ≤ 0.01). Using ROC analysis, presence of ≤3 of 7 risk variables had a positive predictive value of 87.5% and negative predictive value of 50.0% for use of UF alone (area under the curve 0.801; 95% CI: 0.638-0.965, p = 0.002). Pediatric cardiac patients treated with ECMO and UF who require CRRT demonstrate worse outcomes versus UF alone. A novel clinical tool may assist in stratifying patients at UF initiation.

  View details for DOI 10.1097/MAT.0000000000001924

  View details for PubMedID 36947828

• Intraoperative continuous renal replacement therapy in critically ill pediatric liver transplant recipients; a case series Furukawa, L. K., Wolke, O. N., Gallo, A., Sutherland, S., Mendoza, J. WILEY. 2023

  View details for Web of Science ID 001002465500100

• Impact of the Magnitude and Timing of Fluid Overload on Outcomes in Critically Ill Children: A Report From the Multicenter International Assessment of Worldwide Acute Kidney Injury, Renal Angina, and Epidemiology (AWARE) Study. Critical care medicine Selewski, D. T., Gist, K. M., Basu, R. K., Goldstein, S. L., Zappitelli, M., Soranno, D. E., Mammen, C., Sutherland, S. M., Askenazi, D. J., Ricci, Z., Akcan-Arikan, A., Gorga, S. M., Gillespie, S. E., Woroniecki, R. 2023

  Abstract

  With the recognition that fluid overload (FO) has a detrimental impact on critically ill children, the critical care nephrology community has focused on identifying clinically meaningful targets for intervention. The current study aims to evaluate the epidemiology and outcomes associated with FO in an international multicenter cohort of critically ill children. The current study also aims to evaluate the association of FO at predetermined clinically relevant thresholds and time points (FO ≥ 5% and FO ≥ 10% at the end of ICU days 1 and 2) with outcomes.Prospective cohort study.Multicenter, international collaborative of 32 pediatric ICUs.A total of 5,079 children and young adults admitted consecutively to pediatric ICUs as part of the Assessment of the Worldwide Acute Kidney Injury, Renal Angina and Epidemiology Study.None.The FO thresholds at the time points of interest occurred commonly in the cohort (FO ≥ 5%Day1 in 38.1% [n = 1753], FO ≥ 10%Day1 in 11.7% [n = 537], FO ≥ 5%Day2 in 53.3% [n = 1,539], FO ≥ 10%Day2 in 25.1% [n = 724]). On Day1, multivariable modeling demonstrated that FO ≥ 5% was associated with fewer ICU-free days, and FO ≥ 10% was associated with higher mortality and fewer ICU and ventilator-free days. On multivariable modeling, FO-peak, Day2 FO ≥ 5%, and Day2 FO ≥ 10% were associated with higher mortality and fewer ICU and ventilator-free days.This study found that mild-to-moderate FO as early as at the end of ICU Day1 is associated with adverse outcomes. The current study fills an important void in the literature by identifying critical combinations of FO timing and quantity associated with adverse outcomes (FO ≥ 5%Day1, FO ≥10%Day1, FO ≥ 5%Day2, and FO ≥ 10%Day2). Those novel findings will help guide the development of interventional strategies and trials targeting the treatment and prevention of clinically relevant FO.

  View details for DOI 10.1097/CCM.0000000000005791

  View details for PubMedID 36821787

• Chronic implications of an acute disease: Long-term outcomes in pediatric Acute Kidney Injury Survivors. The Journal of pediatrics Sutherland, S. M. 2022

  View details for DOI 10.1016/j.jpeds.2022.10.017

  View details for PubMedID 36252862

• Consensus-Based Recommendations on Priority Activities to Address Acute Kidney Injury in Children: A Modified Delphi Consensus Statement. JAMA network open Goldstein, S. L., Akcan-Arikan, A., Alobaidi, R., Askenazi, D. J., Bagshaw, S. M., Barhight, M., Barreto, E., Bayrakci, B., Bignall, O. N., Bjornstad, E., Brophy, P. D., Chanchlani, R., Charlton, J. R., Conroy, A. L., Deep, A., Devarajan, P., Dolan, K., Fuhrman, D. Y., Gist, K. M., Gorga, S. M., Greenberg, J. H., Hasson, D., Ulrich, E. H., Iyengar, A., Jetton, J. G., Krawczeski, C., Meigs, L., Menon, S., Morgan, J., Morgan, C. J., Mottes, T., Neumayr, T. M., Ricci, Z., Selewski, D., Soranno, D. E., Starr, M., Stanski, N. L., Sutherland, S. M., Symons, J., Tavares, M. S., Vega, M. W., Zappitelli, M., Ronco, C., Mehta, R. L., Kellum, J., Ostermann, M., Basu, R. K. 2022; 5 (9): e2229442

  Abstract

  Increasing evidence indicates that acute kidney injury (AKI) occurs frequently in children and young adults and is associated with poor short-term and long-term outcomes. Guidance is required to focus efforts related to expansion of pediatric AKI knowledge.To develop expert-driven pediatric specific recommendations on needed AKI research, education, practice, and advocacy.At the 26th Acute Disease Quality Initiative meeting conducted in November 2021 by 47 multiprofessional international experts in general pediatrics, nephrology, and critical care, the panel focused on 6 areas: (1) epidemiology; (2) diagnostics; (3) fluid overload; (4) kidney support therapies; (5) biology, pharmacology, and nutrition; and (6) education and advocacy. An objective scientific review and distillation of literature through September 2021 was performed of (1) epidemiology, (2) risk assessment and diagnosis, (3) fluid assessment, (4) kidney support and extracorporeal therapies, (5) pathobiology, nutrition, and pharmacology, and (6) education and advocacy. Using an established modified Delphi process based on existing data, workgroups derived consensus statements with recommendations.The meeting developed 12 consensus statements and 29 research recommendations. Principal suggestions were to address gaps of knowledge by including data from varying socioeconomic groups, broadening definition of AKI phenotypes, adjudicating fluid balance by disease severity, integrating biopathology of child growth and development, and partnering with families and communities in AKI advocacy.Existing evidence across observational study supports further efforts to increase knowledge related to AKI in childhood. Significant gaps of knowledge may be addressed by focused efforts.

  View details for DOI 10.1001/jamanetworkopen.2022.29442

  View details for PubMedID 36178697

• Kidney Replacement Therapy in Low Birth Weight Preterm Newborns. Pediatrics Sutherland, S. M., Davis, A. S., Powell, D., Tanaka, J., Woo, M., Josephs, S., Wong, C. J. 2022

  Abstract

  Managing newborns with kidney failure is a complex undertaking; even under ideal circumstances, dialysis is technically challenging and available therapies are designed for adults. These issues are exacerbated in smaller newborns, and intervention has traditionally not been offered in those below a certain weight threshold. Ethical concerns abound and patients deemed too small for dialysis are typically transitioned to comfort or palliative care. However, many of these neonates are otherwise healthy and would be considered survivable if kidney replacement therapy were available. To challenge the existing paradigm, we present 7 preterm, low birth weight neonates with end-stage kidney disease who were successfully managed using an innovative approach to kidney replacement therapy. These newborns had a median gestational age of 32 weeks (interquartile range [IQR], 32-35) and a median birth weight of 1.58 kg (IQR, 1.41-2.01). Kidney replacement therapy was initiated at a median age of 16 days (IQR, 1.5-40) and a weight of 1.85 kg (IQR, 1.57-2.1). Five of the 7 newborns (71%) survived to hospital discharge. Kidney replacement therapy was provided using 3F and 4F single lumen catheters and a modified ultrafiltration device. Patients experienced excellent metabolic control, and fluid homeostasis was achieved in the first week of life. Furthermore, survivors experienced physiologic weight gain and linear growth throughout their hospitalization. These findings, although preliminary, are encouraging for our smallest patients with kidney failure and suggest that survivability thresholds should be reexamined. At a minimum, neonatologists should be aware that novel approaches exist and may be considered for these challenging patients.

  View details for DOI 10.1542/peds.2022-056570

  View details for PubMedID 35945293

• Post-operative Morbidity and Mortality After Fontan Procedure in Patients with Heterotaxy and Other Situs Anomalies. Pediatric cardiology Duong, S. Q., Zaniletti, I., Lopez, L., Sutherland, S. M., Shin, A. Y., Collins, R. T. 1800

  Abstract

  Heterotaxy is a complex, multisystem disorder associated with single ventricle heart disease and decreased survival. Ciliary dysfunction is common in heterotaxy and other situs abnormalities (H/SA) and may increase post-operative complications. We hypothesized that patients with H/SA have increased respiratory and renal morbidities and increased in-hospital mortality after Fontan procedure. We queried the Pediatric Health Information System database for hospitalizations with ICD-9/10 codes for Fontan procedure in patients aged 1 through 11years from 2004 to 2019. H/SA was identified by codes for dextrocardia, situs inversus, asplenia/polysplenia, or atrial isomerism and compared to non-H/SA controls. Outcomes were in-hospital mortality or heart transplantation, ECMO, hemodialysis, length of stay (LOS), and mechanical ventilation or vasoactive medication use≥4days. We adjusted estimates with multivariable logistic regression. Of 7897 patients at 50 centers, 1366 (17%) met criteria for H/SA. H/SA had worse outcomes for all study measures: death/transplantation (1.9 vs 1.1%, OR 1.74 (95% CI 1.01-3.03); p=0.047), ECMO (3.7 vs 2.3%, OR 1.74 (1.28-2.35); p<0.001), hemodialysis (2.1 vs 1.2%, OR 1.66 (1.06-2.59); p=0.026), prolonged mechanical ventilation (13.2% vs 7.6%, OR 1.85 (1.53-2.25); p<0.001) and vasoactive medication use (29.4 vs 19.7%, OR 1.65 (1.43-1.90), and longer LOS (11 (8-17) vs 9 (7-14) days; p<0.001). H/SA is associated with increased cardiovascular, renal, and respiratory morbidity, as well as in-hospital mortality after Fontan procedure. Attention to renal and respiratory needs may improve outcomes in this difficult population. The relationship between ciliary dysfunction and lung and renal morbidity should be explored further.

  View details for DOI 10.1007/s00246-021-02804-w

  View details for PubMedID 35064275

• Renal Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference. Pediatrics Fitzgerald, J. C., Basu, R. K., Fuhrman, D. Y., Gorga, S. M., Hassinger, A. B., Sanchez-Pinto, L. N., Selewski, D. T., Sutherland, S. M., Akcan-Arikan, A. 1800; 149 (Supplement_1): S66-S73

  Abstract

  CONTEXT: Renal dysfunction is associated with poor outcomes in critically ill children.OBJECTIVE: To evaluate the current evidence for criteria defining renal dysfunction in critically ill children and association with adverse outcomes. To develop contemporary consensus criteria for renal dysfunction in critically ill children.DATA SOURCES: PubMed and Embase were searched from January 1992 to January 2020.STUDY SELECTION: Included studies evaluated critically ill children with renal dysfunction, performance characteristics of assessment tools for renal dysfunction, and outcomes related to mortality, functional status, or organ-specific or other patient-centered outcomes. Studies with adults or premature infants (≤36 weeks' gestational age), animal studies, reviews, case series, and studies not published in English with inability to determine eligibility criteria were excluded.DATA EXTRACTION: Data were extracted from included studies into a standard data extraction form by task force members.RESULTS: The systematic review supported the following criteria for renal dysfunction: (1) urine output <0.5 mL/kg per hour for ≥6 hours and serum creatinine increase of 1.5 to 1.9 times baseline or ≥0.3 mg/dL, or (2) urine output <0.5 mL/kg per hour for ≥12 hours, or (3) serum creatinine increase ≥2 times baseline, or (4) estimated glomerular filtration rate <35 mL/minute/1.73 m2, or (5) initiation of renal replacement therapy, or (6) fluid overload ≥20%. Data also support criteria for persistent renal dysfunction and for high risk of renal dysfunction.LIMITATIONS: All included studies were observational and many were retrospective.CONCLUSIONS: We present consensus criteria for renal dysfunction in critically ill children.

  View details for DOI 10.1542/peds.2021-052888J

  View details for PubMedID 34970682

• Immune System Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference. Pediatrics Hall, M. W., Carcillo, J. A., Cornell, T. 1800; 149 (Supplement_1): S91-S98

  Abstract

  CONTEXT: Immune system dysfunction is poorly represented in pediatric organ dysfunction definitions.OBJECTIVE: To evaluate evidence for criteria that define immune system dysfunction in critically ill children and associations with adverse outcomes and develop consensus criteria for the diagnosis of immune system dysfunction in critically ill children.DATA SOURCES: We conducted electronic searches of PubMed and Embase from January 1992 to January 2020, using medical subject heading terms and text words to define immune system dysfunction and outcomes of interest.STUDY SELECTION: Studies of critically ill children with an abnormality in leukocyte numbers or function that is currently measurable in the clinical laboratory in which researchers assessed patient-centered outcomes were included. Studies of adults or premature infants, animal studies, reviews and commentaries, case series (≤10 subjects), and studies not published in English with inability to determine eligibility criteria were excluded.DATA EXTRACTION: Data were abstracted from eligible studies into a standard data extraction form along with risk of bias assessment by a task force member.RESULTS: We identified the following criteria for immune system dysfunction: (1) peripheral absolute neutrophil count <500 cells/muL, (2) peripheral absolute lymphocyte count <1000 cells/muL, (3) reduction in CD4+ lymphocyte count or percentage of total lymphocytes below age-specific thresholds, (4) monocyte HLA-DR expression <30%, or (5) reduction in ex vivo whole blood lipopolysaccharide-induced TNFalpha production capacity below manufacturer-provided thresholds.LIMITATIONS: Many measures of immune system function are currently limited to the research environment.CONCLUSIONS: We present consensus criteria for the diagnosis of immune system dysfunction in critically ill children.

  View details for DOI 10.1542/peds.2021-052888N

  View details for PubMedID 34970674

• Monitoring Approaches for a Pediatric Chronic Kidney Disease Machine Learning Model. Applied clinical informatics Morse, K. E., Brown, C., Fleming, S., Todd, I., Powell, A., Russell, A., Scheinker, D., Sutherland, S. M., Lu, J., Watkins, B., Shah, N. H., Pageler, N. M., Palma, J. P. 2022; 13 (2): 431-438

  Abstract

  OBJECTIVE: The purpose of this study is to evaluate the ability of three metrics to monitor for a reduction in performance of a chronic kidney disease (CKD) model deployed at a pediatric hospital.METHODS: The CKD risk model estimates a patient's risk of developing CKD 3 to 12 months following an inpatient admission. The model was developed on a retrospective dataset of 4,879 admissions from 2014 to 2018, then run silently on 1,270 admissions from April to October, 2019. Three metrics were used to monitor its performance during the silent phase: (1) standardized mean differences (SMDs); (2) performance of a "membership model"; and (3) response distribution analysis. Observed patient outcomes for the 1,270 admissions were used to calculate prospective model performance and the ability of the three metrics to detect performance changes.RESULTS: The deployed model had an area under the receiver-operator curve (AUROC) of 0.63 in the prospective evaluation, which was a significant decrease from an AUROC of 0.76 on retrospective data (p=0.033). Among the three metrics, SMDs were significantly different for 66/75 (88%) of the model's input variables (p <0.05) between retrospective and deployment data. The membership model was able to discriminate between the two settings (AUROC=0.71, p <0.0001) and the response distributions were significantly different (p <0.0001) for the two settings.CONCLUSION: This study suggests that the three metrics examined could provide early indication of performance deterioration in deployed models' performance.

  View details for DOI 10.1055/s-0042-1746168

  View details for PubMedID 35508197

• Pediatric Organ Dysfunction Information Update Mandate (PODIUM) Contemporary Organ Dysfunction Criteria: Executive Summary. Pediatrics Bembea, M. M., Agus, M., Akcan-Arikan, A., Alexander, P., Basu, R., Bennett, T. D., Bohn, D., Brandao, L. R., Brown, A., Carcillo, J. A., Checchia, P., Cholette, J., Cheifetz, I. M., Cornell, T., Doctor, A., Eckerle, M., Erickson, S., Farris, R. W., Faustino, E. V., Fitzgerald, J. C., Fuhrman, D. Y., Giuliano, J. S., Guilliams, K., Gaies, M., Gorga, S. M., Hall, M., Hanson, S. J., Hartman, M., Hassinger, A. B., Irving, S. Y., Jeffries, H., Jouvet, P., Kannan, S., Karam, O., Khemani, R. G., Kissoon, N., Lacroix, J., Laussen, P., Leclerc, F., Lee, J. H., Leteurtre, S., Lobner, K., McKiernan, P. J., Menon, K., Monagle, P., Muszynski, J. A., Odetola, F., Parker, R., Pathan, N., Pierce, R. W., Pineda, J., Prince, J. M., Robinson, K. A., Rowan, C. M., Ryerson, L. M., Sanchez-Pinto, L. N., Schlapbach, L. J., Selewski, D. T., Shekerdemian, L. S., Simon, D., Smith, L. S., Squires, J. E., Squires, R. H., Sutherland, S. M., Ouellette, Y., Spaeder, M. C., Srinivasan, V., Steiner, M. E., Tasker, R. C., Thiagarajan, R., Thomas, N., Tissieres, P., Traube, C., Tucci, M., Typpo, K. V., Wainwright, M. S., Ward, S. L., Watson, R. S., Weiss, S., Whitney, J., Willson, D., Wynn, J. L., Yeyha, N., Zimmerman, J. J. 1800; 149 (Supplement_1): S1-S12

  Abstract

  Prior criteria for organ dysfunction in critically ill children were based mainly on expert opinion. We convened the Pediatric Organ Dysfunction Information Update Mandate (PODIUM) expert panel to summarize data characterizing single and multiple organ dysfunction and to derive contemporary criteria for pediatric organ dysfunction. The panel was composed of 88 members representing 47 institutions and 7 countries. We conducted systematic reviews of the literature to derive evidence-based criteria for single organ dysfunction for neurologic, cardiovascular, respiratory, gastrointestinal, acute liver, renal, hematologic, coagulation, endocrine, endothelial, and immune system dysfunction. We searched PubMed and Embase from January 1992 to January 2020. Study identification was accomplished using a combination of medical subject headings terms and keywords related to concepts of pediatric organ dysfunction. Electronic searches were performed by medical librarians. Studies were eligible for inclusion if the authors reported original data collected in critically ill children; evaluated performance characteristics of scoring tools or clinical assessments for organ dysfunction; and assessed a patient-centered, clinically meaningful outcome. Data were abstracted from each included study into an electronic data extraction form. Risk of bias was assessed using the Quality in Prognosis Studies tool. Consensus was achieved for a final set of 43 criteria for pediatric organ dysfunction through iterative voting and discussion. Although the PODIUM criteria for organ dysfunction were limited by available evidence and will require validation, they provide a contemporary foundation for researchers to identify and study single and multiple organ dysfunction in critically ill children.

  View details for DOI 10.1542/peds.2021-052888B

  View details for PubMedID 34970673

• Impact of a clinical pathway on acute kidney injury in patients undergoing heart transplant. Pediatric transplantation Algaze, C. A., Margetson, T. D., Sutherland, S. M., Kwiatkowski, D. M., Maeda, K., Navaratnam, M., Samreth, S. P., Price, E. P., Zook, N. B., Yang, J. K., Hollander, S. A. 2021: e14166

  Abstract

  BACKGROUND: To evaluate the impact of a clinical pathway on the incidence and severity of acute kidney injury in patients undergoing heart transplant.METHODS: This was a 2.5-year retrospective evaluation using 3years of historical controls within a cardiac intensive care unit in an academic children's hospital. Patients undergoing heart transplant between May 27, 2014, and April 5, 2017 (pre-pathway) and May 1, 2017, and November 30, 2019 (pathway) were included. The clinical pathway focused on supporting renal perfusion through hemodynamic management, avoiding or delaying nephrotoxic medications, and providing pharmacoprophylaxis against AKI.RESULTS: There were 57 consecutive patients included. There was an unadjusted 20% reduction in incidence of any acute kidney injury (p=.05) and a 17% reduction in Stage 2/3 acute kidney injury (p=.09). In multivariable adjusted analysis, avoidance of Stage 2/3 acute kidney injury was independently associated with the clinical pathway era (AOR -1.3 [95% CI -2.5 to -0.2]; p=.03), achieving a central venous pressure of or less than 12mmHg (AOR -1.3 [95% CI -2.4 to -0.2]; p=.03) and mean arterial pressure above 60mmHg (AOR -1.6 [95% CI -3.1 to -0.01]; p=.05) in the first 48h post-transplant, and older age at transplant (AOR - 0.2 [95% CI -0.2 to -0.06]; p=.002).CONCLUSIONS: This report describes a renal protection clinical pathway associated with a reduction in perioperative acute kidney injury in patients undergoing heart transplant and highlights the importance of normalizing perioperative central venous pressure and mean arterial blood pressure to support optimal renal perfusion.

  View details for DOI 10.1111/petr.14166

  View details for PubMedID 34727417

• Intraoperative and Postoperative Hemodynamic Predictors of Acute Kidney Injury in Pediatric Heart Transplant Recipients JOURNAL OF PEDIATRIC INTENSIVE CARE Hollander, S. A., Chung, S., Reddy, S., Zook, N., Yang, J., Vella, T., Navaratnam, M., Price, E., Sutherland, S. M., Algaze, C. A. 2021

  View details for DOI 10.1055/s-0041-1736336

  View details for Web of Science ID 000704825900002

• Association of Plasma Uremic Solute Levels with Residual Kidney Function in Children on Peritoneal Dialysis. Clinical journal of the American Society of Nephrology : CJASN Ganesan, L., O'Brien, F., Sirich, T., Plummer, N., Sheth, R., Fajardo, C., Brakeman, P., Sutherland, S., Meyer, T. 2021

  Abstract

  Background and objectives. Residual native kidney function confers health benefits in dialysis patients. It can facilitate control of extracellular volume and inorganic ion concentrations. Residual kidney function can also limit the accumulation of uremic solutes. This study assessed whether lower plasma concentrations of uremic solutes were associated with residual kidney function in pediatric patients on peritoneal dialysis. Design, setting, participants, and measurements. Samples were analyzed from 29 pediatric peritoneal dialysis patients including 13 without residual kidney function and 10 with residual kidney function. Metabolomic analysis by untargeted mass spectrometry compared plasma solute levels in patients with and without residual kidney function. Dialytic and residual clearances of selected solutes were also measured by assays employing chemical standards. Results. Metabolomic analysis showed that plasma levels of 256 uremic solutes in patients with residual kidney function averaged 64 (51-81 IQR) percent of the values in patients without residual kidney function who had similar total Kt/Vurea The plasma levels were significantly lower for 59 of the 256 solutes in the patients with residual kidney function and significantly higher for none. Assays employing chemical standards showed that residual kidney function provides a higher portion of the total clearance for non-urea solutes than it does for urea. Conclusions. Concentrations of many uremic solutes are lower in peritoneal dialysis patients with residual kidney function than in those without residual kidney function receiving similar treatment as assessed by Kt/Vurea.

  View details for DOI 10.2215/CJN.01430121

  View details for PubMedID 34233922

• Cumulative Application of Creatinine and Urine Output Staging Optimizes the Kidney Disease: Improving Global Outcomes Definition and Identifies Increased Mortality Risk in Hospitalized Patients With Acute Kidney Injury. Critical care medicine Sutherland, S. M., Kaddourah, A., Gillespie, S. E., Soranno, D. E., Woroniecki, R. P., Basu, R. K., Zappitelli, M., Assessment of the Worldwide Acute Kidney Injury, R. A. 2021

  Abstract

  OBJECTIVES: Acute kidney injury is diagnosed according to creatinine and urine output criteria. Traditionally, both are applied, and a severity stage (1-3) is conferred based upon the more severe of the two; information from the other criteria is discarded. Physiologically, however, rising creatinine and oliguria represent two distinct types of renal dysfunction. We hypothesized that using the information from both criteria would more accurately characterize acute kidney injury severity and outcomes.DESIGN: Prospective cohort study.SETTING: Multicenter, international collaborative of ICUs.PATIENTS: Three thousand four hundred twenty-nine children and young adults admitted consecutively to ICUs as part of the Assessment of the Worldwide Acute Kidney Injury, Renal Angina and Epidemiology Study.MEASUREMENTS AND MAIN RESULTS: The Kidney Disease: Improving Global Outcomes creatinine and urine output acute kidney injury criteria were applied sequentially, and the two stages were summed, generating an Acute Kidney Injury (AKI) Score ranging from 1 to 6. The primary outcome was 28-day mortality; secondary outcomes were time until ICU discharge and nonrecovery from acute kidney injury. Models considered associations with AKI Score, assessing the relationship unadjusted and adjusted for covariates. Twenty-eight-day mortality and nonrecovery from acute kidney injury were modeled using logistic regression. For 28-day ICU discharge, competing risks analysis was performed. Although AKI Scores 1-3 had similar mortality to no Acute Kidney Injury, AKI Scores 4-6 were associated with increased mortality. Relative to No Acute Kidney Injury, AKI Scores 1-6 were less likely to be discharged from the ICU within 28 days. Relative to AKI Score 1, AKI Scores 2-6 were associated with higher risk of nonrecovery. Within the traditional Kidney Disease: Improving Global Outcomes Stage 3 acute kidney injury cohort, when compared with AKI Score 3, AKI Scores 4-6 had increased mortality, AKI Scores 5-6 had prolonged time to ICU discharge, and AKI Score 6 experienced higher nonrecovery rates.CONCLUSIONS: Cumulative application of the creatinine and urine output criteria characterizes renal excretory and fluid homeostatic dysfunction simultaneously. This Acute Kidney Injury score more comprehensively describes the outcome implications of severe acute kidney injury than traditional staging methods.

  View details for DOI 10.1097/CCM.0000000000005073

  View details for PubMedID 33938717

• Quality improvement goals for pediatric acute kidney injury: pediatric applications of the 22nd Acute Disease Quality Initiative (ADQI) conference. Pediatric nephrology (Berlin, Germany) Selewski, D. T., Askenazi, D. J., Kashani, K., Basu, R. K., Gist, K. M., Harer, M. W., Jetton, J. G., Sutherland, S. M., Zappitelli, M., Ronco, C., Goldstein, S. L., Mottes, T. A. 2021

  View details for DOI 10.1007/s00467-020-04828-5

  View details for PubMedID 33433708

• Using kinetic eGFR to identify acute kidney injury risk in children undergoing cardiac transplantation. Pediatric research Dasgupta, M. N., Montez-Rath, M. E., Hollander, S. A., Sutherland, S. M. 2021

  Abstract

  Acute kidney injury (AKI) is common following pediatric cardiac transplantation. Since no treatments exist, strategies focus on early identification and prevention. Kinetic glomerular filtration rate (kGFR) was developed to assess renal function in the non-steady state. Although used to predict AKI in adults, kGFR has not been explored in children. Our study examines AKI and the ability of kGFR to identify AKI risk in pediatric heart transplant recipients.One hundred and seventy-five patients under 21 years who underwent cardiac transplantation at Lucile Packard Children's Hospital between September 2007-December 2017 were included. kGFR1 was calculated using pre-operative and immediate post-operative creatinines; kGFR2 was calculated with the first two post-operative creatinines. The primary outcome was AKI as defined by the Kidney Disease: Improving Global Outcomes criteria.One hundred and thirty-one (75%) and 78 (45%) patients developed AKI and severe AKI, respectively; 5 (2.9%) required dialysis. kGFR was moderately associated with post-operative AKI risk. The adjusted area under the curve (AUC) for kGFR1 was 0.72 (discovery) and 0.65 (validation). The AUC for kGFR2 was 0.72 (discovery) and 0.68 (validation).AKI is pervasive in children undergoing cardiac transplant, particularly in the 24 h after surgery. kGFR moderately identifies AKI risk and may represent a novel risk stratification technique.Our research suggests that kGFR, a dynamic assessment of renal function that uses readily available laboratory values, can moderately identify AKI risk in children undergoing cardiac transplantation. Current published studies on kGFR are in adult populations; this study represents the first formal study of kGFR in a pediatric population. kGFR may serve as an early AKI indicator, allowing providers to implement preventative strategies sooner in a patient's clinical course.

  View details for DOI 10.1038/s41390-020-01307-3

  View details for PubMedID 33446916

• Hemodynamic Predictors of Renal Function After Pediatric Left Ventricular Assist Device Implantation. ASAIO journal (American Society for Artificial Internal Organs : 1992) Chen, C. Y., Montez-Rath, M. E., May, L. J., Maeda, K., Hollander, S. A., Rosenthal, D. N., Krawczeski, C. D., Sutherland, S. M. 2021; 67 (12): 1335-1341

  Abstract

  Although renal function often improves after pediatric left ventricular assist device (LVAD) implantation, recovery is inconsistent. We aimed to identify hemodynamic parameters associated with improved renal function after pediatric LVAD placement. A single-center retrospective cohort study was conducted in patients less than 21 years who underwent LVAD placement between June 2004 and December 2015. The relationship between hemodynamic parameters and estimated glomerular filtration rate (eGFR) was assessed using univariate and multivariate modeling. Among 54 patients, higher preoperative central venous pressure (CVP) was associated with eGFR improvement after implantation (p = 0.012). However, 48 hours postimplantation, an increase in CVP from baseline was associated with eGFR decline over time (p = 0.01). In subgroup analysis, these associations were significant only for those with normal pre-ventricular assist device renal function (p = 0.026). In patients with preexisting renal dysfunction, higher absolute CVP values 48 and 72 hours after implantation predicted better renal outcome (p = 0.005). Our results illustrate a complex relationship between ventricular function, volume status, and renal function. Additionally, they highlight the challenge of using CVP to guide management of renal dysfunction in pediatric heart failure. Better methods for evaluating right heart function and volume status are needed to improve our understanding of how hemodynamics impact renal function in this population.

  View details for DOI 10.1097/MAT.0000000000001460

  View details for PubMedID 34860188

• Improving the quality of neonatal acute kidney injury care: neonatal-specific response to the 22nd Acute Disease Quality Initiative (ADQI) conference. Journal of perinatology : official journal of the California Perinatal Association Harer, M. W., Selewski, D. T., Kashani, K., Basu, R. K., Gist, K. M., Jetton, J. G., Sutherland, S. M., Zappitelli, M., Goldstein, S. L., Mottes, T. A., Askenazi, D. J. 2020

  Abstract

  With the adoption of standardized neonatal acute kidney injury (AKI) definitions over the past decade and the concomitant surge in research studies, the epidemiology of and risk factors for neonatal AKI have become much better understood. Thus, there is now a need to focus on strategies designed to improve AKI care processes with the goal of reducing the morbidity and mortality associated with neonatal AKI. The 22nd Acute Dialysis/Disease Quality Improvement (ADQI) report provides a framework for such quality improvement in adults at risk for AKI and its sequelae. While many of the concepts can be translated to neonates, there are a number of specific nuances which differ in neonatal AKI care. A group of experts in pediatric nephrology and neonatology came together to provide neonatal-specific responses to each of the 22nd ADQI consensus statements.

  View details for DOI 10.1038/s41372-020-00810-z

  View details for PubMedID 32892210

• EXTRACORPOREAL PHOTOPHERESIS: TREATMENT FOR STEROID RESISTANT REJECTION IN PEDIATRIC LIVER TRANSPLANT RECIPIENTS Depper, J., North, L., Mandac, C. A., Marshall, A. F., Schwartz, S., Mock, A., Sutherland, S., Esquivel, C. O., Bonham, C. LIPPINCOTT WILLIAMS & WILKINS. 2020: S550

  View details for Web of Science ID 000618872101232

• Impaired Tubular Secretion of Organic Solutes in Acute Kidney Injury. Kidney360 O'Brien, F. J., Mair, R. D., Plummer, N. S., Meyer, T. W., Sutherland, S. M., Sirich, T. L. 2020; 1 (8): 724-730

  Abstract

  Impairment of kidney function is routinely assessed by measuring the accumulation of creatinine, an organic solute cleared largely by glomerular filtration. We tested whether the clearance of solutes that undergo tubular secretion is reduced in proportion to the clearance of creatinine in humans with AKI.Four endogenously produced organic solutes (phenylacetylglutamine [PAG], hippurate [HIPP], indoxyl sulfate [IS], and p-cresol sulfate [PCS]) were measured in spot urine and plasma samples from ten patients with AKI and 17 controls. Fractional clearance relative to creatinine was calculated to assess tubular secretion. Fractional clearance values were calculated in terms of the free, unbound levels of HIPP, IS, and PCS that bind to plasma proteins.Fractional clearance values for PAG, HIPP, IS, and PCS were >1.0 in patients with AKI as well as controls, indicating that these solutes were still secreted by the tubules of the injured kidneys. Fractional clearance values were, however, significantly lower in patients with AKI than controls, indicating that kidney injury reduced tubular secretion more than glomerular filtration (AKI versus control: PAG, 2.1±0.7 versus 4.6±1.4, P<0.001; HIPP, 10±5 versus 15±7, P=0.02; IS, 10±6 versus 28±7, P<0.001; PCS, 3.3±1.8 versus 10±3, P<0.001). Free plasma levels rose out of proportion to total plasma levels for each of the bound solutes in AKI, so that calculating their fractional clearance in terms of their total plasma levels failed to reveal their impaired secretion.Tubular secretion of organic solutes can be reduced out of proportion to glomerular filtration in AKI. Impaired secretion of protein-bound solutes may be more reliably detected when clearances are expressed in terms of their free, unbound levels in the plasma.

  View details for DOI 10.34067/kid.0001632020

  View details for PubMedID 35252876

  View details for PubMedCentralID PMC8815732

• Clinical evaluation of the Prismaflex HF 20 set and Prismaflex system 7.10 for acute continuous kidney replacement therapy (CKRT) in children. Pediatric nephrology (Berlin, Germany) Munshi, R., Lee-Son, K., Hackbarth, R. M., Quigley, R., Sutherland, S. M., Echeverri, J., Goldstein, S. L. 2020

  Abstract

  BACKGROUND: Continuous kidney replacement therapy (CKRT) is a common modality for treatment of severe acute kidney injury (AKI) in children. Adult technologies routinely utilized to provide this therapy have a large extracorporeal volume. The Prismaflex HF20 filter set has a relatively low extracorporeal blood volume of 60mL, which provides technological benefit for smaller children compared with current filter sets available in the USA.METHODS: We conducted a multicenter, open-label single group study to evaluate whether the Prismaflex HF20 filter set delivers efficacious and safe CKRT to support patients with AKI, fluid overload, or both in pediatric patients weighing ≥8 to 20kg.RESULTS: Twenty-three patients were enrolled between April 24, 2016 and April 8, 2018. The mean reduction in blood urea nitrogen from baseline to 24h was 58.12±20.08% (95% CI, -68.45 and -47.79 (p=0.0008)). Median cumulative normalized effluent rate at 24h was 60.8mL/kg/h (25.9, 83.7). None of the patients participating in the study suffered a serious adverse event; thus, no obvious safety concerns were noted.CONCLUSIONS: We suggest that the Prismaflex HF20 filter set used in conjunction with the Prismaflex System Software Version 7.10 or 7.20 is a suitable alternative to larger filter sets for use in pediatric patients weighing less than 20kg. Graphical abstract.

  View details for DOI 10.1007/s00467-020-04664-7

  View details for PubMedID 32607769

• Myelin bodies in LMX1B-associated nephropathy: potential for misdiagnosis. Pediatric nephrology (Berlin, Germany) Lei, L., Oh, G., Sutherland, S., Abra, G., Higgins, J., Sibley, R., Troxell, M., Kambham, N. 2020

  Abstract

  BACKGROUND: Myelin figures, or zebra bodies, seen on electron microscopy were historically considered pathognomonic of Fabry disease, a rare lysosomal storage disorder caused by alpha-galactosidase A deficiency and associated with X-linked recessive mode of inheritance. More recently, iatrogenic phospholipidosis has emerged as an important alternate cause of myelin figures in the kidney.METHODS: We report two families with autosomal dominant nephropathy presenting with proteinuria and microscopic hematuria, and the kidney biopsies were notable for the presence of myelin figures and zebra bodies.RESULTS: Laboratory and genetic work-up for Fabry disease was negative. Genetic testing in both families revealed the same heterozygous missense mutation in LMX1B (C.737G>A, p.Arg246Gln). LMX1B mutations are known to cause nail-patella syndrome, featuring dysplastic nails and patella with or without nephropathy, as well as isolated LMX1B-associated nephropathy in the absence of extrarenal manifestations.CONCLUSIONS: LMX1B mutation-associated nephropathy should be considered in hereditary cases of proteinuria and/or hematuria, even in the absence of unique glomerular basement membrane changes indicative of nail-patella syndrome. In addition, LMX1B mutation should be included in the differential diagnosis of myelin figures and zebra bodies on kidney biopsy, so as to avoid a misdiagnosis.

  View details for DOI 10.1007/s00467-020-04564-w

  View details for PubMedID 32356190

• Acute kidney injury in hospitalized children: consequences and outcomes PEDIATRIC NEPHROLOGY Uber, A. M., Sutherland, S. M. 2020; 35 (2): 213–20

  View details for DOI 10.1007/s00467-018-4128-7

  View details for Web of Science ID 000509712800005

• Acute kidney injury and chronic kidney disease after combined heart-liver transplant in patients with congenital heart disease: A retrospective case series. Pediatric transplantation Lee, A. n., Concepcion, W. n., Gonzales, S. n., Sutherland, S. M., Hollander, S. A. 2020: e13833

  Abstract

  Although it is known that children undergoing heart transplantation are at increased risk for both AKI and CKD, renal function following CHLT remains understudied. All pediatric CHLT patients from 2006 to 2019 were included. The prevalence of AKI in the first 7 post-operative days, renal recovery at 30 post-operative days, and CKD were ascertained. AKI was defined as an increase in creatinine greater than 1.5 times baseline, and CKD, as an eCrCl less than 90 mL/min/1.73 m2 . The need for RRT was also analyzed. 10 patients were included, with an average age of 20 years and an average listing time of 130 days. Preoperatively, the median eCrCl was 91.12 mL/min/m2 (IQR 70.51, 127.75 min/mL/m2 ). 5 (50%) patients had CKD, with 4 at stage 2 and 1 at stage 3. AKI occurred post-operatively in 3 of 9 (33%) patients: 2 at stage 1 and 1 at stage 2. 2 (67%) resolved by 7 days. Of the 5 patients who reached their 1-year follow-up, 1 (20%) had stage 3 CKD. Among 2 patients, neither had CKD at 5 years. One patient required RRT 2 weeks after CHLT. Despite an increased prevalence of preoperative CKD, patients undergoing CHLT have a lower AKI prevalence than those receiving an isolated heart or liver transplant. Of those with AKI, early renal recovery is common, although at 1 year CKD remains present in 20%. Among long-term survivors, normal renal function is achievable.

  View details for DOI 10.1111/petr.13833

  View details for PubMedID 32985770

• Baseline creatinine determination method impacts association between acute kidney injury and clinical outcomes. Pediatric nephrology (Berlin, Germany) Russell, W. A., Scheinker, D. n., Sutherland, S. M. 2020

  Abstract

  Current consensus definition for acute kidney injury (AKI) does not specify how baseline serum creatinine should be determined. We assessed how baseline determination impacted AKI incidence and association between AKI and clinical outcomes.We retrospectively applied empirical (measured serum creatinine) and imputed (age/height) baseline estimation methods to pediatric patients discharged between 2014 and 2019 from an academic hospital. Using each method, we estimated AKI incidence and assessed area under ROC curve (AUROC) for AKI as a predictor of three clinical outcomes: application of AKI billing code (proxy for more clinically overt disease), inpatient mortality, and post-hospitalization chronic kidney disease.Incidence was highly variable across baseline methods (12.2-26.7%). Incidence was highest when lowest pre-admission creatinine was used if available and Schwartz bedside equation was used to impute one otherwise. AKI was more predictive of application of an AKI billing code when baseline was imputed universally, regardless of pre-admission values (AUROC 80.7-84.9%) than with any empirical approach (AUROC 64.5-76.6%). AKI was predictive of post-hospitalization CKD when using universal imputation baseline methods (AUROC 67.0-74.6%); AKI was not strongly predictive of post-hospitalization CKD when using empirical baseline methods (AUROC 46.4-58.5%). Baseline determination method did not affect the association between AKI and inpatient mortality.Method of baseline determination influences AKI incidence and association between AKI and clinical outcomes, illustrating the need for standard criteria. Imputing baseline for all patients, even when preadmission creatinine is available, may identify a more clinically relevant subset of the disease.

  View details for DOI 10.1007/s00467-020-04789-9

  View details for PubMedID 33095322

• Policy in pediatric nephrology: successes, failures, and the impact on disparities. Pediatric nephrology (Berlin, Germany) Krissberg, J. R., Sutherland, S. M., Chamberlain, L. J., Wise, P. H. 2020

  Abstract

  Pediatric nephrology has a history rooted in pediatric advocacy and has made numerous contributions to child health policy affecting pediatric kidney diseases. Despite this progress, profound social disparities remain for marginalized and socially vulnerable children with kidney disease. Different risk factors, such as genetic predisposition, environmental factors, social risk factors, or health care access influence the emergence and progression of pediatric kidney disease, as well as access to life-saving interventions, leading to disparate outcomes. This review will summarize the breadth of literature on social determinants of health in children with kidney disease worldwide and highlight policy-based initiatives that mitigate the adverse social factors to generate greater equity in pediatric kidney disease.

  View details for DOI 10.1007/s00467-020-04755-5

  View details for PubMedID 32968856

• Acute Kidney Injury in Children Hospitalized With Diarrheal Illness in the United States. Hospital pediatrics Bradshaw, C., Han, J., Chertow, G. M., Long, J., Sutherland, S. M., Anand, S. 2019

  Abstract

  OBJECTIVES: To determine the incidence, correlates, and consequences of acute kidney injury (AKI) among children hospitalized with diarrheal illness in the United States.METHODS: Using data from Kids' Inpatient Database in 2009 and 2012, we studied children hospitalized with a primary diagnosis of diarrheal illness (weighted N = 113195). We used the International Classification of Diseases, Ninth Revision, Clinical Modification, diagnosis codes 584.5 to 584.9 to capture AKI. We calculated the incidence, correlates, and consequences (mortality, length of stay [LOS], and costs) of AKI associated with hospitalized diarrheal illness using stepwise logistic regression and generalized linear models.RESULTS: The average incidence of AKI in children hospitalized with diarrheal illness was 0.8%. Hospital location and teaching status were associated with the odds of AKI, as were older age, solid organ transplant, hypertension, chronic kidney disease, and rheumatologic and hematologic conditions. The development of AKI in hospitalized diarrheal illness was associated with an eightfold increase in the odds of in-hospital mortality (odds ratio 8.0; 95% confidence interval [CI] 4.2-15.4). AKI was associated with prolonged LOS (mean increase 3.0 days; 95% CI 2.3-3.8) and higher hospital cost (mean increase $9241; 95% CI $4661-$13820).CONCLUSIONS: Several demographic factors and comorbid conditions are associated with the risk of AKI in children hospitalized with diarrheal illness. Although rare, development of AKI in this common pediatric condition is associated with increased mortality, LOS, and hospital cost.

  View details for DOI 10.1542/hpeds.2019-0220

  View details for PubMedID 31771950

• A prospective multi-center quality improvement initiative (NINJA) indicates a reduction in nephrotoxic acute kidney injury in hospitalized children. Kidney international Goldstein, S. L., Dahale, D., Kirkendall, E. S., Mottes, T., Kaplan, H., Muething, S., Askenazi, D. J., Henderson, T., Dill, L., Somers, M. J., Kerr, J., Gilarde, J., Zaritsky, J., Bica, V., Brophy, P. D., Misurac, J., Hackbarth, R., Steinke, J., Mooney, J., Ogrin, S., Chadha, V., Warady, B., Ogden, R., Hoebing, W., Symons, J., Yonekawa, K., Menon, S., Abrams, L., Sutherland, S., Weng, P., Zhang, F., Walsh, K. 2019

  Abstract

  Nephrotoxic medication (NTMx) exposure is a common cause of acute kidney injury (AKI) in hospitalized children. The Nephrotoxic Injury Negated by Just-in time Action (NINJA) program decreased NTMx associated AKI (NTMx-AKI) by 62% at one center. To further test the program, we incorporated NINJA across nine centers with the goal of reducing NTMx exposure and, consequently, AKI rates across these centers. NINJA screens all non-critically ill hospitalized patients for high NTMx exposure (over three medications on the same day or an intravenous aminoglycoside over three consecutive days), and then recommends obtaining a daily serum creatinine level in exposed patients for the duration of, and two days after, exposure ending. Additionally, substitution of equally efficacious but less nephrotoxic medications for exposed patients starting the day of exposure was recommended when possible. The main outcome was AKI as defined by the Kidney Disease Improving Global Outcomes (KDIGO) serum creatinine criteria (increase of 50% or 0.3 mg/dl over baseline). The primary outcome measure was AKI episodes per 1000 patient-days. Improvement was defined by statistical process control methodology and confirmed by Autoregressive Integrated Moving Average (ARIMA) modeling. Eight consecutive bi-weekly measure rates in the same direction from the established baseline qualified as special cause change for special process control. We observed a significant and sustained 23.8% decrease in NTMx-AKI rates by statistical process control analysis and by ARIMA modeling; similar to those of the pilot single center. Thus, we have successfully applied the NINJA program to multiple pediatric institutions yielding decreased AKI rates.

  View details for DOI 10.1016/j.kint.2019.10.015

  View details for PubMedID 31980139

• Evaluation and management of elevated blood pressures in hospitalized children PEDIATRIC NEPHROLOGY Chaudhuri, A., Sutherland, S. M. 2019; 34 (10): 1671–81

  View details for DOI 10.1007/s00467-018-4070-8

  View details for Web of Science ID 000502375800004

• IDENTIFICATION OF ACUTE KIDNEY INJURY IN PEDIATRIC CYSTIC FIBROSIS PATIENTS Bio, L., Schwenk, H. T., Wise, R., Yeung, J., Qureshi, L., Sutherland, S. WILEY. 2019: S284

  View details for Web of Science ID 000484544000435

• Antimicrobial Disposition During Pediatric Continuous Renal Replacement Therapy Using an Ex Vivo Model. Critical care medicine Purohit, P. J., Elkomy, M. H., Frymoyer, A., Sutherland, S. M., Drover, D. R., Hammer, G. B., Su, F. 2019

  Abstract

  OBJECTIVES: Little is known on the impact of continuous renal replacement therapy on antimicrobial dose requirements in children. In this study, we evaluated the pharmacokinetics of commonly administered antimicrobials in an ex vivo continuous renal replacement therapy model.DESIGN: An ex vivo continuous renal replacement therapy circuit was used to evaluate drug-circuit interactions and determine the disposition of five commonly used antimicrobials (meropenem, piperacillin, liposomal amphotericin B, caspofungin, and voriconazole).SETTING: University research laboratory.PATIENTS: None.INTERVENTIONS: Antimicrobials were administered into a reservoir containing whole human blood. The reservoir was connected to a pediatric continuous renal replacement therapy circuit programmed for a 10 kg child. Continuous renal replacement therapy was performed in the hemodiafiltration mode and in three phases correlating with three different continuous renal replacement therapy clearance rates: 1) no clearance (0 mL/kg/hr, to measure adsorption), 2) low clearance (20 mL/kg/hr), and 3) high clearance (40 mL/kg/hr). Blood samples were drawn directly from the reservoir at baseline and at 5, 20, 60, and 180 minutes during each phase. Five independent continuous renal replacement therapy runs were performed to assess inter-run variability. Antimicrobial concentrations were measured using validated liquid chromatography-mass spectrometry assays. A closed-loop, flow-through pharmacokinetic model was developed to analyze concentration-time profiles for each drug.MEASUREMENTS AND MAIN RESULTS: Circuit adsorption of antimicrobials ranged between 13% and 27%. Meropenem, piperacillin, and voriconazole were cleared by the continuous renal replacement therapy circuit and clearance increased with increasing continuous renal replacement therapy clearance rates (7.66 mL/min, 4.97 mL/min, and 2.67 mL/min, respectively, for high continuous renal replacement therapy clearance). Amphotericin B and caspofungin had minimal circuit clearance and did not change with increasing continuous renal replacement therapy clearance rates.CONCLUSIONS: Careful consideration of drug-circuit interactions during continuous renal replacement therapy is essential for appropriate drug dosing in critically ill children. Antimicrobials have unique adsorption and clearance profiles during continuous renal replacement therapy, and this knowledge is important to optimize antimicrobial therapy.

  View details for DOI 10.1097/CCM.0000000000003895

  View details for PubMedID 31306179

• Renal injury and recovery in pediatric patients after ventricular assist device implantation and cardiac transplant. Pediatric transplantation Hollander, S. A., Cantor, R. S., Sutherland, S. M., Koehl, D. A., Pruitt, E., McDonald, N., Kirklin, J. K., Ravekes, W. J., Ameduri, R., Chrisant, M., Hoffman, T. M., Lytrivi, I. D., Conway, J. 2019: e13477

  Abstract

  BACKGROUND: The use of ventricular assist devices (VADs) in children with heart failure may be of particular benefit to those with accompanying renal failure, as improved renal function is seen in some, but not all recipients. We hypothesized that persistent renal dysfunction at 7days and/or 1month after VAD implantation would predict chronic kidney disease (CKD) 1year after heart transplantation (HT).METHODS: Linkage analysis of all VAD patients enrolled in both the PEDIMACS and PHTS registries between 2012 and 2016. Persistent acute kidney injury (P-AKI), defined as a serum creatinine ≥1.5* baseline, was assessed at post-implant day 7. Estimated glomerular filtration rate (eGFR) was determined at implant, 30days thereafter, and 12months post-HT. Pre-implant eGFR, eGFR normalization (to ≥90mL/min/1.73m2 ), and P-AKI were used to predict post-HT CKD (eGFR <90mL/min/1.73m2 ).RESULTS: The mean implant eGFR was 85.4±46.5mL/min/1.73m2 . P-AKI was present in 19/188 (10%). Mean eGFR at 1month post-VAD implant was 131.1±62.1mL/min/1.73m2 , significantly increased above baseline (P<0.001). At 1year post-HT (n=133), 60 (45%) had CKD. Lower pre-implant eGFR was associated with post-HT CKD (OR 0.99, CI: 0.97-0.99, P=0.005); P-AKI was not (OR 0.96, CI: 0.3-3.0, P=0.9). Failure to normalize renal function 30days after implant was highly associated with CKD at 1year post-transplant (OR 12.5, CI 2.8-55, P=0.003).CONCLUSIONS: Renal function improves after VAD implantation. Lower pre-implant eGFR and failure to normalize renal function during the support period are risk factors for CKD development after HT.

  View details for DOI 10.1111/petr.13477

  View details for PubMedID 31124590

• Oliguria and Acute Kidney Injury in Critically Ill Children: Implications for Diagnosis and Outcomes PEDIATRIC CRITICAL CARE MEDICINE Kaddourah, A., Basu, R. K., Goldstein, S. L., Sutherland, S. M., Assessment Worldwide Acute Kidney 2019; 20 (4): 332–39

  View details for DOI 10.1097/PCC.0000000000001866

  View details for Web of Science ID 000469383200011

• Oliguria and Acute Kidney Injury in Critically Ill Children: Implications for Diagnosis and Outcomes. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies Kaddourah, A., Basu, R. K., Goldstein, S. L., Sutherland, S. M., Assessment of Worldwide Acute Kidney Injury, R. A. 2019

  Abstract

  OBJECTIVES: Consensus definitions for acute kidney injury are based on changes in serum creatinine and urine output. Although the creatinine criteria have been widely applied, the contribution of the urine output criteria remains poorly understood. We evaluated these criteria individually and collectively to determine their impact on the diagnosis and outcome of severe acute kidney injury.DESIGN AND SETTING: Post hoc analysis of Assessment of Worldwide Acute Kidney Injury, Renal Angina, and Epidemiology study-a prospective international observational multicenter study.PATIENTS: Critically ill children enrolled in Assessment of Worldwide Acute Kidney Injury, Renal Angina and, Epidemiology database.MEASUREMENT: To assess the differential impact of creatinine and urine output criteria on severe acute kidney injury (Kidney Disease: Improving Global Outcomes stage ≥ 2). Patients were divided into four cohorts: no-severe acute kidney injury, severe acute kidney injury by creatinine criteria only, severe acute kidney injury by urine output criteria only, and severe acute kidney injury by both creatinine and urine output criteria.RESULTS: Severe acute kidney injury occurred in 496 of 3,318 children (14.9%); 343 (69.2%) were creatinine criteria only, 90 (18.1%) were urine output criteria only, and 63 (12.7%) were both creatinine and urine output criteria. Twenty-eight-day mortality for creatinine criteria only and urine output criteria only patients was similar (6.7% vs 7.8%) and higher than those without severe acute kidney injury (2.9%; p < 0.01). Both creatinine and urine output criteria patients had higher mortality than creatinine criteria only and urine output criteria only patients (38.1%; p < 0.001). Compared with patients without severe acute kidney injury, the relative risk of receiving dialysis increased from 9.1 (95% CI, 3.9-21.2) in creatinine criteria only, to 28.2 (95% CI, 11.8-67.7) in urine output criteria only, to 165.7 (95% CI, 86.3-318.2) in both creatinine and urine output criteria (p < 0.01).CONCLUSIONS: Nearly one in five critically ill children with acute kidney injury do not experience increase in serum creatinine. These acute kidney injury events, which are only identified by urine output criteria, are associated with comparably poor outcomes as those diagnosed by changes in creatinine. Children meeting both criteria had worse outcomes than those meeting only one. We suggest oliguria represents a risk factor for poorer outcomes among children who develop acute kidney injury. Application of both the creatinine and urine output criteria leads to a more comprehensive epidemiologic assessment of acute kidney injury and identifies a subset of children with acute kidney injury who are at higher risk for morbidity and mortality.

  View details for PubMedID 30676490

• Big Data and Pediatric Acute Kidney Injury: The Promise of Electronic Health Record Systems. Frontiers in pediatrics Sutherland, S. M. 2019; 7: 536

  Abstract

  Over the last decade, our understanding of acute kidney injury (AKI) has evolved considerably. The development of a consensus definition standardized the approach to identifying and investigating AKI in children. As a result, pediatric AKI epidemiology has been refined and the consequences of renal injury are better established. Similarly, "big data" methodologies experienced a dramatic evolution and maturation, leading the critical care community to explore potential AKI/big data synergies. One such concept with tremendous potential is electronic health record (EHR) enabled informatics. Much of the promise surrounding these approaches is due to the unique position of the EHR which sits at the intersection of data accumulation and care delivery. EHR data is generated simply via the provision of routine clinical care and should be considered "big" from the standpoint of volume, variety, and velocity as a myriad of diverse elements accumulate rapidly in real time, spontaneously generating an immense dataset. This massive dataset interfaces directly with providers which creates tremendous opportunity. AKI can be diagnosed more accurately, AKI-related care can be optimized, and subsequent outcomes can be improved. Although applying big data concepts to the EHR has proven more challenging than originally thought, we have seen much success and continue to explore its potential. In this review article, we will discuss the EHR in the context of big data concepts, describe approaches applied to date, examine the challenges surrounding optimal application, and explore future directions.

  View details for DOI 10.3389/fped.2019.00536

  View details for PubMedID 31993409

• Plasma pseudouridine levels reflect body size in children on hemodialysis. Pediatric nephrology (Berlin, Germany) O'Brien, F. J., Sirich, T. L., Taussig, A. n., Fung, E. n., Ganesan, L. L., Plummer, N. S., Brakeman, P. n., Sutherland, S. M., Meyer, T. W. 2019

  Abstract

  Dialysis in children as well as adults is prescribed to achieve a target spKt/Vurea, where Vurea is the volume of distribution of urea. Waste solute production may however be more closely correlated with body surface area (BSA) than Vurea which rises in proportion with body weight. Plasma levels of waste solutes may thus be higher in smaller patients when targeting spKt/Vurea since they have higher BSA relative to body weight. This study measured levels of pseudouridine (PU), a novel marker solute whose production is closely proportional to BSA, to test whether prescription of dialysis to a target spKt/Vurea results in higher plasma levels of PU in smaller children.PU and urea nitrogen (ureaN) were measured in plasma and dialysate at the midweek hemodialysis session in 20 pediatric patients, with BSA ranging from 0.65-1.87m2. Mathematical modeling was employed to estimate solute production rates and average plasma solute levels.The dialytic clearance (Kd) of PU was proportional to that of ureaN (average KdPU/KdUreaN 0.69 ± 0.13, r2 0.84, p < 0.001). Production of PU rose in proportion with BSA (r2 0.57, p < 0.001). The pretreatment plasma level of PU was significantly higher in smaller children (r2 0.20, p = 0.051) while the pretreatment level of ureaN did not vary with size.Prescribing dialysis based on urea kinetics may leave uremic solutes at higher levels in small children. Measurement of a solute produced proportional to BSA may provide a better index of dialysis adequacy than measurement of urea.

  View details for DOI 10.1007/s00467-019-04369-6

  View details for PubMedID 31728748

• Nephrotoxins and nephrotoxic acute kidney injury. Pediatric nephrology (Berlin, Germany) Uber, A. M., Sutherland, S. M. 2019

  Abstract

  Although the concept of nephrotoxicity has been recognized for more than 80 years, interest in nephrotoxins has intensified dramatically over the past two decades. Much of this attention has rightfully been focused on pharmaceutical agents and iatrogenic harm; however, it is important for providers to recognize that nephrotoxins can be found in naturally occurring substances as well. Although nephrotoxins exist in a myriad of forms, the means by which they induce injury can be organized into a few categories. For most of these agents, regardless of the mechanism, the final common pathway is acute kidney injury (AKI). Unfortunately, therapeutic options are limited and no treatments currently exist to reverse nephrotoxic AKI once it occurs. As a result, current strategies focus on increased awareness, nephrotoxin avoidance, early injury detection, and mitigation of disease severity. The goal of this review is to summarize our current understanding of nephrotoxic mechanisms and the epidemiology of nephrotoxic AKI. Additionally, avoidance and preventative strategies are discussed, screening approaches are suggested, and chronic monitoring recommendations are made.

  View details for DOI 10.1007/s00467-019-04397-2

  View details for PubMedID 31646405

• Pediatric acute kidney injury and the subsequent risk for chronic kidney disease: is there cause for alarm? PEDIATRIC NEPHROLOGY Sigurjonsdottir, V. K., Chaturvedi, S., Mammen, C., Sutherland, S. M. 2018; 33 (11): 2047–55

  View details for DOI 10.1007/s00467-017-3870-6

  View details for Web of Science ID 000445363600004

• Nephrotoxin exposure and acute kidney injury in critically ill children undergoing congenital cardiac surgery PEDIATRIC NEPHROLOGY Uber, A. M., Montez-Rath, M. E., Kwiatkowski, D. M., Krawczeski, C. D., Sutherland, S. M. 2018; 33 (11): 2193–99

  View details for DOI 10.1007/s00467-018-4010-7

  View details for Web of Science ID 000445363600019

• Acute kidney injury in hospitalized children: consequences and outcomes. Pediatric nephrology (Berlin, Germany) Uber, A. M., Sutherland, S. M. 2018

  Abstract

  Over the past decade, the nephrology and critical care communities have adopted a consensus approach to diagnosing acute kidney injury (AKI) and, as a result, we have seen transformative changes in our understanding of pediatric AKI epidemiology. The data regarding outcomes among neonates and children who develop AKI have become far more robust and AKI has been clearly linked with an increased need for mechanical ventilation, longer inpatient stays, and higher mortality. Though AKI was historically thought to be self-limited, we now know that renal recovery is far from universal, particularly when AKI is severe; the absence of recovery from AKI also carries longitudinal prognostic implications. AKI survivors, especially those without full recovery, are at risk for chronic renal sequelae including proteinuria, hypertension, and chronic kidney disease. This review comprehensively describes AKI-related outcomes across the entire pediatric age spectrum, using the most rigorous studies to identify the independent effects of AKI events.

  View details for PubMedID 30386936

• Evaluation and management of elevated blood pressures in hospitalized children. Pediatric nephrology (Berlin, Germany) Chaudhuri, A., Sutherland, S. M. 2018

  Abstract

  Elevated blood pressures (BP) are common among hospitalized children and, if not recognized and treated promptly, can lead to potentially significant consequences. Even though we have normative BP data and well-developed guidelines for the diagnosis and management of hypertension (HTN) in the ambulatory setting, our understanding of elevated BPs and their relationship to HTN in hospitalized children is limited. Several issues have hampered our ability to diagnose and manage HTN in the inpatient setting including the common presence of physiologic conditions, which are associated with transient BP elevations (i.e., pain or anxiety), non-standard approaches to BP measurement, a lack of clarity regarding appropriate diagnostic and therapeutic thresholds, and marginal outcome data. The purpose of this review is to highlight the issues and challenges surrounding BP monitoring, assessment of elevated BPs, and the diagnosis of HTN in hospitalized children. Extrapolating from currently available clinical practice guidelines and utilizing the best data available, we aim to provide guidelines regarding evaluation and treatment of elevated BP in hospitalized children.

  View details for PubMedID 30171355

• Electronic Health Record-Enabled Big-Data Approaches to Nephrotoxin-Associated Acute Kidney Injury Risk Prediction PHARMACOTHERAPY Sutherland, S. M. 2018; 38 (8): 804-812

  View details for DOI 10.1002/phar.2150

  View details for Web of Science ID 000441005900004

• Nephrotoxin exposure and acute kidney injury in critically ill children undergoing congenital cardiac surgery. Pediatric nephrology (Berlin, Germany) Uber, A. M., Montez-Rath, M. E., Kwiatkowski, D. M., Krawczeski, C. D., Sutherland, S. M. 2018

  Abstract

  BACKGROUND: Though acute kidney injury (AKI) is often multifactorial, investigators are now emphasizing the specific contribution of nephrotoxins. This study examines the epidemiology of nephrotoxin exposure and nephrotoxin-associated AKI among children undergoing congenital heart surgery (CHS).METHODS: This is a retrospective cohort study of children admitted following CHS between June 1, 2014, and September 30, 2014. Nephrotoxins were defined according to the Nephrotoxic Injury Negated by Just-in-time-Action (NINJA) collaborative; high nephrotoxin exposure was defined as receipt of ≥3 nephrotoxins concurrently. AKI was diagnosed according to KDIGO creatinine criteria. Severe AKI was defined as KDIGO stage ≥2. Poisson models were used to compute adjusted relative risk (aRR) of high nephrotoxin exposure for AKI.RESULTS: One hundred fifty-four children (median age 20.4months, IQR 2.3-59.5) were included. One hundred thirty-one (85.1%) received at least one nephrotoxin; 32 (20.8%) received ≥3 nephrotoxins. The most commonly administered medications were ketorolac (n=74, 48.1%), aspirin (n=62, 40.3%), ibuprofen (n=51, 33.1%), vancomycin (n=39, 25.3%), piperacillin/tazobactam (n=35, 22.7%), and enalapril (n=14, 9.1%). AKI occurred more commonly in those exposed to ≥3 nephrotoxins (62.5 vs. 50.8%); this was not statistically significant after adjusting for confounders (aRR=1.2, 95% CI 0.9-1.7). Severe AKI was similar between those with and without high nephrotoxin exposure (21.9 vs. 19.7%, p=0.78).CONCLUSIONS: Nephrotoxin use is common following pediatric CHS. While we found no association between high nephrotoxin exposure and AKI, this may be related to the multifactorial nature of AKI in this population. For many common nephrotoxins, less injurious agents exist and nephrotoxin exposure may represent a modifiable risk factor for AKI.

  View details for PubMedID 29987455

• Electronic Health Record-Enabled Big-Data Approaches to Nephrotoxin-Associated Acute Kidney Injury Risk Prediction. Pharmacotherapy Sutherland, S. M. 2018

  Abstract

  Nephrotoxin-associated acute kidney injury (NTx-AKI) has become one of the most common causes of AKI among hospitalized adults and children; across acute and intensive care populations, exposure to nephrotoxins accounts for 15-25% of AKI. Although some interventions have shown promise in observational studies, no treatments currently exist for NTx-AKI once it occurs. Thus, nearly all effective strategies are aimed at prevention. The primary obstacle to prevention is risk prediction and the determination of which patients are more likely to develop NTx-AKI when exposed to medications with nephrotoxic potential. Historically, traditional statistical modeling has been applied to previously recognized clinical risk factors to identify predictors of NTx-AKI. However, increased electronic health record adoption and the evolution of "big-data" approaches to predictive analytics may offer a unique opportunity to prevent NTx-AKI events. This article describes prior and current approaches to NTx-AKI prediction and offers three novel use cases for electronic health record-enabled NTx-AKI forecasting and risk profiling. This article is protected by copyright. All rights reserved.

  View details for PubMedID 29885015

• Long-Term Consequences of Acute Kidney Injury in Children CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Sutherland, S. M. 2018; 13 (5): 677–78

  View details for PubMedID 29678894

  View details for PubMedCentralID PMC5969471

• Failure to Improve Renal Function Following VAD Placement Predicts Renal Injury and Chronic Kidney Disease Following Cardiac Transplant Hollander, S. A., Pruitt, E., Sutherland, S. M., Cantor, R. S., Kirklin, J., Ravekes, W. J., Ameduri, R., Chrisant, M., Hoffman, T., Lytrivi, I., Conway, J. ELSEVIER SCIENCE INC. 2018: S117–S118

  View details for Web of Science ID 000429934300274

• CHILDREN TOLERATE INTRADIALYTIC ORAL NUTRITION JOURNAL OF RENAL CARE South, A. M., Fainman, B., Sutherland, S. M., Wong, C. J. 2018; 44 (1): 38–43

  Abstract

  People undergoing haemodialysis (HD) often have poor nutrition, which in turn can contribute to worse outcomes. Inadequate nutrition has a particularly deleterious effect on growth and neurocognitive development, as well as mortality, in children and adolescents. Nutritional supplementation can improve outcomes but can be difficult to administer.Determine the tolerability of intradialytic oral nutrition in children and adolescents.A cross-sectional quality improvement study in an outpatient paediatric HD unit. Intervention was intradialytic oral nutritional supplementation provided as protein bars and/or meals.Children and adolescents undergoing outpatient HD who were able to participate in surveys and eat by mouth.Adverse effects and symptoms on nurse- and patient-reported surveys, respectively. Relationships between the predictor variables and the outcomes were assessed using generalised estimating equations.The majority of children felt better after eating on dialysis (72%) with no adverse effects (80%). On unadjusted analyses and confirmed with generalised estimating equation modelling, children who reported being hungry felt better after eating on dialysis, despite being more likely to have adverse effects.The study demonstrates that our children and adolescents feel better after eating on HD with minimal adverse effects. The finding that hungry patients are more likely to feel better despite having a higher likelihood of an adverse effect demonstrates the tolerability of eating on HD. Intradialytic oral nutrition could be a safe and well-tolerated opportunity to provide supplemental nutrition to paediatric HD patients and improve outcomes.

  View details for PubMedID 29230952

• Pediatric acute kidney injury and the subsequent risk for chronic kidney disease: is there cause for alarm? Pediatric nephrology (Berlin, Germany) Sigurjonsdottir, V. K., Chaturvedi, S., Mammen, C., Sutherland, S. M. 2018

  Abstract

  Acute kidney injury (AKI) is characterized clinically as an abrupt decline in renal function marked by reduced excretion of waste products, disordered electrolytes, and disrupted fluid homeostasis. The recent development of a standardized AKI definition has transformed our understanding of AKI epidemiology and outcomes. We now know that in the short term, children with AKI experience greater morbidity and mortality; additionally, observational studies have established that chronic renal sequelae are far more common after AKI events than previously realized. Many of these studies suggest that patients who develop AKI are at greater risk for the subsequent development of chronic kidney disease (CKD). The goal of this review is to critically evaluate the data regarding the association between AKI and CKD in children. Additionally, we describe best practice approaches for future studies, including the use of consensus AKI criteria, the application of rigorous definitions for CKD and renal sequelae, and the inclusion of non-AKI comparator groups. Finally, based upon existing data, we suggest an archetypal approach to follow-up care for the AKI survivors who may be at greater CKD risk, including children with more severe AKI, those who endure repeated AKI episodes, patients who do not experience full recovery, and those with pre-existing CKD.

  View details for PubMedID 29374316

• Acute Kidney Injury and Big Data ACUTE KIDNEY INJURY - BASIC RESEARCH AND CLINICAL PRACTICE Sutherland, S. M., Goldstein, S. L., Bagshaw, S. M. edited by Ding, Rosner, M. H., Ronco, C. 2018; 193: 55–67

  Abstract

  The recognition of a standardized, consensus definition for acute kidney injury (AKI) has been an important milestone in critical care nephrology, which has facilitated innovation in prevention, quality of care, and outcomes research among the growing population of hospitalized patients susceptible to AKI. Concomitantly, there have been substantial advances in "big data" technologies in medicine, including electronic health records (EHR), data registries and repositories, and data management and analytic methodologies. EHRs are increasingly being adopted, clinical informatics is constantly being refined, and the field of EHR-enabled care improvement and research has grown exponentially. While these fields have matured independently, integrating the two has the potential to redefine and integrate AKI-related care and research. AKI is an ideal condition to exploit big data health care innovation for several reasons: AKI is common, increasingly encountered in hospitalized settings, imposes meaningful risk for adverse events and poor outcomes, has incremental cost implications, and has been plagued by suboptimal quality of care. In this concise review, we discuss the potential applications of big data technologies, particularly modern EHR platforms and health data repositories, to transform our capacity for AKI prediction, detection, and care quality.

  View details for DOI 10.1159/000484963

  View details for Web of Science ID 000435333400007

  View details for PubMedID 29393191

• Acute Kidney Injury in Children ADVANCES IN CHRONIC KIDNEY DISEASE Sutherland, S. M., Kwiatkowski, D. M. 2017; 24 (6): 380–87

  View details for DOI 10.1053/j.ackd.2017.09.007

  View details for Web of Science ID 000418988700007

• Acute Kidney Injury in Children. Advances in chronic kidney disease Sutherland, S. M., Kwiatkowski, D. M. 2017; 24 (6): 380-387

  Abstract

  Acute kidney injury (AKI) has become one of the more common complications seen among hospitalized children. The development of a consensus definition has helped refine the epidemiology of pediatric AKI, and we now have a far better understanding of its incidence, risk factors, and outcomes. Strategies for diagnosing AKI have extended beyond serum creatinine, and the most current data underscore the diagnostic importance of oliguria as well as introduce the concept of urinary biomarkers of kidney injury. As AKI has become more widespread, we have seen that it is associated with a number of adverse consequences including longer lengths of stay and greater mortality. Though effective treatments do not currently exist for AKI once it develops, we hope that the diagnostic and definitional strides seen recently translate to the testing and development of more effective interventions.

  View details for DOI 10.1053/j.ackd.2017.09.007

  View details for PubMedID 29229169

• Acute kidney injury in pediatric patients BEST PRACTICE & RESEARCH-CLINICAL ANAESTHESIOLOGY Kwiatkowski, D. M., Sutherland, S. M. 2017; 31 (3): 427–39

  View details for DOI 10.1016/j.bpa.2017.08.007

  View details for Web of Science ID 000418098100012

• Acute kidney injury in pediatric patients. Best practice & research. Clinical anaesthesiology Kwiatkowski, D. M., Sutherland, S. M. 2017; 31 (3): 427-439

  Abstract

  Acute kidney injury (AKI) is highly prevalent among hospitalized children, especially those who are critically ill. The incorporation of pediatric elements into consensus definitions has led to a greater understanding of pediatric AKI epidemiology, risk factors, and outcomes. The best available data suggest that AKI occurs in 5% and 27% of non-critically ill and critically ill children, respectively. Additionally, AKI and fluid overload are independently associated with worse outcomes including mortality. Currently, the diagnosis of AKI relies upon urine output and creatinine measurements, both of which pose unique problems in children. However, novel biomarker discovery and new risk stratification techniques have led to enhanced detection and diagnostic strategies. Although no specific treatments exist, strategies designed to prevent AKI are being developed and there is growing evidence that early detection may improve outcomes. We hope that advances in AKI management will follow the diagnostic innovations seen in the past decade.

  View details for DOI 10.1016/j.bpa.2017.08.007

  View details for PubMedID 29248148

• Cardiac Predictors of Renal Recovery After Pediatric Left Ventricular Assist Device (LVAD) Implantation Chen, C., Montez-Rath, M. E., May, L. J., Maeda, K., Hollander, S. A., Rosenthal, D. N., Sutherland, S. M., Krawczeski, C. D. ELSEVIER SCIENCE INC. 2017: S281–S282

  View details for Web of Science ID 000398839801009

• Leveraging Big Data and Electronic Health Records to Enhance Novel Approaches to Acute Kidney Injury Research and Care. Blood purification Sutherland, S. M., Goldstein, S. L., Bagshaw, S. M. 2017; 44 (1): 68-76

  Abstract

  While acute kidney injury (AKI) has been poorly defined historically, a decade of effort has culminated in a standardized, consensus definition. In parallel, electronic health records (EHRs) have been adopted with greater regularity, clinical informatics approaches have been refined, and the field of EHR-enabled care improvement and research has burgeoned. Although both fields have matured in isolation, uniting the 2 has the capacity to redefine AKI-related care and research. This article describes how the application of a consistent AKI definition to the EHR dataset can accurately and rapidly diagnose and identify AKI events. Furthermore, this electronic, automated diagnostic strategy creates the opportunity to develop predictive approaches, optimize AKI alerts, and trace AKI events across institutions, care platforms, and administrative datasets.

  View details for DOI 10.1159/000458751

  View details for PubMedID 28268210

• The Effect of Intradialytic Intralipid Therapy in Pediatric Hemodialysis Patients. Journal of renal nutrition Haskin, O., Sutherland, S. M., Wong, C. J. 2017; 27 (2): 132-137

  Abstract

  Growth of children on maintenance hemodialysis is poor. Oral nutritional supplements are the preferred way to augment nutrition; however, many children have difficulties adhering to prescribed oral supplements. In our unit, we have been utilizing intralipid (IL) therapy as nutritional supplement during hemodialysis sessions. The aim of this study was to assess the safety, efficacy, and benefits of intradialytic IL therapy.A retrospective chart review.Fifteen pediatric hemodialysis patients receiving intradialytic IL therapy for at least 3 months from July 2011 through July 2014.For each patient, anthropometric measurements and laboratory nutritional parameters were compared prior to and at the end of IL therapy. Anthropometric measurements evaluated were dry weight, height, body mass index (BMI), and BMI corrected for height age. Laboratory nutritional parameters evaluated were albumin, normalized protein catabolic rate, predialysis blood urea nitrogen, transferrin, cholesterol, and triglyceride levels. Adverse events during therapy were also noted.Significant improvement was noted in albumin levels, predialysis blood urea nitrogen, and normalized protein catabolic rate during therapy (P = .02; P = .03; P = .03, respectively). Six patients (37.5%) improved their weight standard deviation score, and eight patients (50%) improved their BMI standard deviation score though not statistically significant (P = .59; P = .9, respectively). No significant side effects were noted.Administration of IL alone during hemodialysis is well tolerated with beneficial effects on nutritional parameters. The provision of IL alone is relatively cheap and does not require additional resources. In conjunction with other measures of nutritional support, it can help improve nutritional status of pediatric hemodialysis patients.

  View details for DOI 10.1053/j.jrn.2016.10.003

  View details for PubMedID 27923526

• Fluid overload independent of acute kidney injury predicts poor outcomes in neonates following congenital heart surgery. Pediatric nephrology (Berlin, Germany) Mah, K. E., Hao, S. n., Sutherland, S. M., Kwiatkowski, D. M., Axelrod, D. M., Almond, C. S., Krawczeski, C. D., Shin, A. Y. 2017

  Abstract

  Fluid overload (FO) is common after neonatal congenital heart surgery and may contribute to mortality and morbidity. It is unclear if the effects of FO are independent of acute kidney injury (AKI).This was a retrospective cohort study which examined neonates (age < 30 days) who underwent cardiopulmonary bypass in a university-affiliated children's hospital between 20 October 2010 and 31 December 2012. Demographic information, risk adjustment for congenital heart surgery score, surgery type, cardiopulmonary bypass time, cross-clamp time, and vasoactive inotrope score were recorded. FO [(fluid in-out)/pre-operative weight] and AKI defined by Kidney Disease Improving Global Outcomes serum creatinine criteria were calculated. Outcomes were all-cause, in-hospital mortality and median postoperative hospital and intensive care unit lengths of stay.Overall, 167 neonates underwent cardiac surgery using cardiopulmonary bypass in the study period, of whom 117 met the inclusion criteria. Of the 117 neonates included in the study, 76 (65%) patients developed significant FO (>10%), and 25 (21%) developed AKI ≥ Stage 2. When analyzed as FO cohorts (< 10%,10-20%, > 20% FO), patients with greater FO were more likely to have AKI (9.8 vs. 18.2 vs. 52.4%, respectively, with AKI ≥ stage 2; p = 0.013) and a higher vasoactive-inotrope score, and be premature. In the multivariable regression analyses of patients without AKI, FO was independently associated with hospital and intensive care unit lengths of stay [0.322 extra days (p = 0.029) and 0.468 extra days (p < 0.001), respectively, per 1% FO increase). In all patients, FO was also associated with mortality [odds ratio 1.058 (5.8% greater odds of mortality per 1% FO increase); 95% confidence interval 1.008,1.125;p = 0.032].Fluid overload is an important independent contributor to outcomes in neonates following congenital heart surgery. Careful fluid management after cardiac surgery in neonates with and without AKI is warranted.

  View details for PubMedID 29128923

• Letter to the Editor regarding "Arrhythmias in the paediatric ICU: a prospective study of the rates and predictors of arrhythmias in children without underlying cardiac disease" by Cassel-Choudhury et al. CARDIOLOGY IN THE YOUNG Axelrod, D. M., Frymoyer, A. R., Sutherland, S. M. 2017; 27 (1): 203–4

  View details for DOI 10.1017/S1047951116001128

  View details for Web of Science ID 000398104500031

• Incidence, risk factors, and outcomes of acute kidney injury in adults undergoing surgery for congenital heart disease. Cardiology in the young Kwiatkowski, D. M., Price, E., Axelrod, D. M., Romfh, A. W., Han, B. S., Sutherland, S. M., Krawczeski, C. D. 2016: 1-8

  Abstract

  Acute kidney injury after cardiac surgery is a frequent and serious complication among children with congenital heart disease (CHD) and adults with acquired heart disease; however, the significance of kidney injury in adults after congenital heart surgery is unknown. The primary objective of this study was to determine the incidence of acute kidney injury after surgery for adult CHD. Secondary objectives included determination of risk factors and associations with clinical outcomes.This single-centre, retrospective cohort study was performed in a quaternary cardiovascular ICU in a paediatric hospital including all consecutive patients ⩾18 years between 2010 and 2013.Data from 118 patients with a median age of 29 years undergoing cardiac surgery were analysed. Using Kidney Disease: Improving Global Outcome creatinine criteria, 36% of patients developed kidney injury, with 5% being moderate to severe (stage 2/3). Among higher-complexity surgeries, incidence was 59%. Age ⩾35 years, preoperative left ventricular dysfunction, preoperative arrhythmia, longer bypass time, higher Risk Adjustment for Congenital Heart Surgery-1 category, and perioperative vancomycin use were significant risk factors for kidney injury development. In multivariable analysis, age ⩾35 years and vancomycin use were significant predictors. Those with kidney injury were more likely to have prolonged duration of mechanical ventilation and cardiovascular ICU stay in the univariable regression analysis.We demonstrated that acute kidney injury is a frequent complication in adults after surgery for CHD and is associated with poor outcomes. Risk factors for development were identified but largely not modifiable. Further investigation within this cohort is necessary to better understand the problem of kidney injury.

  View details for PubMedID 27869053

• Management of Peritoneal Dialysis Catheters That Erode Into Bowel: Two Pediatric Case Reports and a Review of the Literature PERITONEAL DIALYSIS INTERNATIONAL South, A. M., Crispin, M. K., Marqueling, A. L., Sutherland, S. M. 2016; 36 (6): 680-700

  Abstract

  Erosion of peritoneal dialysis (PD) catheters into the intestine is a rare complication of PD. Herein, we convey the first reports of 2 pediatric patients undergoing PD who were found to have the catheter eroding into their intestines. They were treated minimally with catheter removal and antibiotics. Definitive repair of the intestinal injury was not performed. These are the first pediatric patients reported with PD catheter erosion. Perforating injuries may be self-limiting, and therefore a more minimal approach may be considered in certain patient populations who do not express overt signs of peritonitis or illness.

  View details for DOI 10.3747/pdi.2016.00029

  View details for Web of Science ID 000389655100016

  View details for PubMedID 27903851

• Theophylline Population Pharmacokinetics and Dosing in Children Following Congenital Heart Surgery With Cardiopulmonary Bypass. Journal of clinical pharmacology Frymoyer, A., Su, F., Grimm, P. C., Sutherland, S. M., Axelrod, D. M. 2016; 56 (9): 1084-1093

  Abstract

  Children undergoing cardiac surgery requiring cardiopulmonary bypass (CPB) frequently develop acute kidney injury due to renal ischemia. Theophylline, which improves renal perfusion via adenosine receptor inhibition, is a potential targeted therapy. However, children undergoing cardiac surgery and CPB commonly have alterations in drug pharmacokinetics. To help understand optimal aminophylline (salt formulation of theophylline) dosing strategies in this population, a population-based pharmacokinetic model was developed using nonlinear mixed-effects modeling (NONMEM) from 71 children (median age: 5 months [90% range: 1 week - 10 years]) who underwent cardiac surgery requiring CPB and received aminophylline as part of a previous randomized controlled trial. A one-compartment model with linear elimination adequately described the pharmacokinetics of theophylline. Weight scaled via allometry was a significant predictor of clearance and volume. In addition, allometric scaled clearance increased with age implemented as a power maturation function. Compared to prior reports in non-cardiac children, theophylline clearance was markedly reduced across age. Applying the final population pharmacokinetic model, optimized empiric dosing regimens were developed via Monte Carlo simulations. Doses 50-75% lower than those recommended in non-cardiac children were needed to achieve target serum concentrations of 5-10 mg/L. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/jcph.697

  View details for PubMedID 26712558

• Recovery From Acute Kidney Injury and CKD Following Heart Transplantation in Children, Adolescents, and Young Adults: A Retrospective Cohort Study. American journal of kidney diseases Hollander, S. A., Montez-Rath, M. E., Axelrod, D. M., Krawczeski, C. D., May, L. J., Maeda, K., Rosenthal, D. N., Sutherland, S. M. 2016; 68 (2): 212-218

  Abstract

  Acute kidney injury (AKI) is common in children following surgery for congenital heart disease and has been associated with poor long-term kidney outcomes. Children undergoing heart transplantation may be at increased risk for the development of both AKI and chronic kidney disease (CKD). This study examines AKI rates in children, adolescents, and young adults after heart transplantation and analyzes the relationship between AKI and CKD in this population.Retrospective cohort study.88 young patients who underwent heart transplantation at Lucile Packard Children's Hospital, Stanford, CA, September 1, 2007, to November 30, 2013.The primary independent variable was AKI within the first 7 postoperative days, ascertained according to the KDIGO (Kidney Disease: Improving Global Outcomes) creatinine criteria (increase in serum creatinine ≥ 1.5 times baseline within 7 days).Recovery from AKI at 3 months, ascertained as serum creatinine level < 1.5 times baseline; and development of CKD at 6 and 12 months, ascertained as estimated glomerular filtration rate < 60mL/min/1.73m(2) for more than 3 months.63 (72%) patients developed AKI; 57% had moderate (stage 2 or severe stage 3) disease. Recovery occurred in 39 of 63 (62%), 50% for stage 2 or 3 versus 78% for stage 1 (P=0.04). At 6 and 12 months, 3 of 82 (4%) and 4 of 76 (5%) developed CKD, respectively. At both time points, CKD was more common in those without recovery (3/22 [14%] vs 0/38 (0%); P=0.04, and 3/17 (18%) vs (0/34) 0%; P=0.03, respectively).Retrospective design, small sample size, and single-center nature of the study.AKI is common after heart transplantation in children, adolescents, and young adults. Nonrecovery from AKI is more common in patients with more severe AKI and is associated with the development of CKD during the first year.

  View details for DOI 10.1053/j.ajkd.2016.01.024

  View details for PubMedID 26970941

• The authors reply. Pediatric critical care medicine Axelrod, D. M., Anglemyer, A., Sutherland, S. M. 2016; 17 (8): 814-815

  View details for DOI 10.1097/PCC.0000000000000841

  View details for PubMedID 27500628

• Letter to the Editor regarding "Arrhythmias in the paediatric ICU: a prospective study of the rates and predictors of arrhythmias in children without underlying cardiac disease" by Cassel-Choudhury et al. Cardiology in the young Axelrod, D. M., Frymoyer, A. R., Sutherland, S. M. 2016: 1-2

  View details for PubMedID 27418191

• Impact of ventricular assist device placement on longitudinal renal function in children with end-stage heart failure. journal of heart and lung transplantation May, L. J., Montez-Rath, M. E., Yeh, J., Axelrod, D. M., Chen, S., Maeda, K., Almond, C. S., Rosenthal, D. N., Hollander, S. A., Sutherland, S. M. 2016; 35 (4): 449-456

  Abstract

  Although ventricular assist devices (VADs) restore hemodynamics in those with heart failure, reversibility of end-organ dysfunction with VAD support is not well characterized. Renal function often improves in adults after VAD placement, but this has not been comprehensively explored in children.Sixty-three children on VAD support were studied. Acute kidney injury (AKI) was defined by Kidney Disease: Improving Global Outcomes criteria. Estimated glomerular filtration rate (eGFR) was determined by the Schwartz method. Generalized linear mixed-effects models compared the pre-VAD and post-VAD eGFR for the cohort and sub-groups with and without pre-VAD renal dysfunction (pre-VAD eGFR < 90 ml/min/1.73 m(2)).The pre-VAD eGFR across the cohort was 84.0 ml/min/1.73 m(2) (interquartile range [IQR] 62.3-122.7), and 55.6% (34 of 63) had pre-VAD renal dysfunction. AKI affected 60.3% (38 of 63), with similar rates in those with and without pre-existing renal dysfunction. Within the cohort, the nadir eGFR occurred 1 day post-operatively (62.9 ml/min/1.73 m(2); IQR, 51.2-88.9 ml/min/1.73 m(2); p < 0.001). By Day 5, however, the eGFR exceeded the baseline (99.0 ml/min/1.73 m(2); IQR, 59.3-146.7 ml/min/1.73 m(2); p = 0.03) and remained significantly higher through the first post-operative week. After adjusting for age, gender, and AKI, the eGFR continued to increase throughout the entire 180-day study period (β = 0.0025; 95% confidence interval, 0.0015-0.0036; p < 0.001). Patients with pre-VAD renal dysfunction experienced the greatest improvement in the eGFR (β = 0.0051 vs β = 0.0013, p < 0.001).Renal dysfunction is prevalent in children with heart failure undergoing VAD placement. Although peri-operative AKI is common, renal function improves substantially in the first post-operative week and for months thereafter. This is particularly pronounced in those with pre-VAD renal impairment, suggesting that VADs may facilitate recovery and maintenance of kidney function in children with advanced heart failure.

  View details for DOI 10.1016/j.healun.2015.10.039

  View details for PubMedID 26653933

• Electronic Health Record-Enabled Research in Children Using the Electronic Health Record for Clinical Discovery. Pediatric clinics of North America Sutherland, S. M., Kaelber, D. C., Downing, N. L., Goel, V. V., Longhurst, C. A. 2016; 63 (2): 251-268

  Abstract

  Initially described more than 50 years ago, electronic health records (EHRs) are now becoming ubiquitous throughout pediatric health care settings. The confluence of increased EHR implementation and the exponential growth of digital data within them, the development of clinical informatics tools and techniques, and the growing workforce of experienced EHR users presents new opportunities to use EHRs to augment clinical discovery and improve pediatric patient care. This article reviews the basic concepts surrounding EHR-enabled research and clinical discovery, including the types and fidelity of EHR data elements, EHR data validation/corroboration, and the steps involved in analytical interrogation.

  View details for DOI 10.1016/j.pcl.2015.12.002

  View details for PubMedID 27017033

• Dexmedetomidine Is Associated With Lower Incidence of Acute Kidney Injury After Congenital Heart Surgery. Pediatric critical care medicine Kwiatkowski, D. M., Axelrod, D. M., Sutherland, S. M., Tesoro, T. M., Krawczeski, C. D. 2016; 17 (2): 128-134

  Abstract

  Recent data have suggested an association between the use of dexmedetomidine and a decreased incidence of acute kidney injury in adult patients after cardiopulmonary bypass. However, no study has focused on this association among pediatric populations where the incidence of acute kidney injury is particularly high and of critical significance. The primary objective of this study was to assess the relationship between the use of postoperative dexmedetomidine and the incidence of acute kidney injury in pediatric patients undergoing cardiopulmonary bypass. The secondary objective was to determine whether there was an association between dexmedetomidine use and duration of mechanical ventilation or cardiovascular ICU stay.Single-center retrospective matched cohort study.A 20-bed quaternary cardiovascular ICU in a university-based pediatric hospital in California.Children less than 18 years old admitted after cardiac surgery with cardiopulmonary bypass between January 1, 2012, and May 31, 2014.None.Data from a cohort of 102 patients receiving dexmedetomidine during the first postoperative day after cardiac surgery were compared to an age- and procedure-matched cohort not receiving dexmedetomidine. Cohorts had similar baseline and demographic characteristics. Patients receiving dexmedetomidine were less likely to develop acute kidney injury (24% vs 36%; odds ratio, 0.54; 95% CI, 0.29-0.99; p = 0.046). After adjusting for age, bypass time, nephrotoxin use, and vasoactive inotropic score, the use of dexmedetomidine was associated with a lower incidence of acute kidney injury with adjusted odds ratio of 0.43 (95% CI, 0.27-0.98; p = 0.048). There was no difference between the cohorts with respect to the duration of mechanical duration (1 d each; p = 0.98) or cardiovascular ICU stays (5 vs 6 d; p = 0.91).The use of a dexmedetomidine infusion in pediatric patients after congenital heart surgery was associated with a decreased incidence of acute kidney injury; however, it was not associated with changes in clinical outcomes. Further prospective study is necessary to validate these findings.

  View details for DOI 10.1097/PCC.0000000000000611

  View details for PubMedID 26673841

• THEOPHYLLINE POPULATION PHARMACOKINETICS AND DOSING IN CHILDREN FOLLOWING CONGENITAL HEART SURGERY WITH CARDIOPULMONARY BYPASS. Frymoyer, A., Su, F., Grimm, P. C., Sutherland, S. M., Axelrod, D. M. WILEY-BLACKWELL. 2016: S84

  View details for Web of Science ID 000368692600299

• A Double-Blinded, Randomized, Placebo-Controlled Clinical Trial of Aminophylline to Prevent Acute Kidney Injury in Children Following Congenital Heart Surgery With Cardiopulmonary Bypass. Pediatric critical care medicine Axelrod, D. M., Sutherland, S. M., Anglemyer, A., Grimm, P. C., Roth, S. J. 2016; 17 (2): 135-143

  Abstract

  Acute kidney injury occurs commonly in children following congenital cardiac surgery with cardiopulmonary bypass and has been associated with increased morbidity and mortality. Aminophylline, a methylxanthine nonselective adenosine receptor antagonist, has been effective in the management of acute kidney injury in certain populations. This study sought to determine whether postoperative administration of aminophylline attenuates acute kidney injury in children undergoing congenital cardiac surgery with cardiopulmonary bypass.Single-center, double-blinded, placebo-controlled, randomized clinical trial.Tertiary center, pediatric cardiovascular ICU.A total of 144 children after congenital heart surgery with cardiopulmonary bypass.Seventy-two patients were randomized to receive aminophylline and 72 patients received placebo. Study drug was administered every 6 hours for 72 hours.The primary outcome variable was the development of any acute kidney injury, defined by the serum creatinine criteria of the Kidney Diseases: Improving Global Outcomes. Secondary outcomes included the development of severe acute kidney injury, time between cardiovascular ICU admission and first successful extubation, percent fluid overload, total fluid balance, urine output, bioelectrical impedance, and serum neutrophil gelatinase-associated lipocalin. The unadjusted rate and severity of acute kidney injury were not different between groups; 43 of 72 (60%) of the treatment group and 36 of 72 (50%) of the placebo group developed acute kidney injury (p = 0.32). Stage 2/3 acute kidney injury occurred in 23 of 72 (32%) of the treatment group and 15 of 72 (21%) of the placebo group (p = 0.18). Secondary outcome measures also demonstrated no significant difference between treatment and placebo groups. Aminophylline administration was safe; no deaths occurred in either group, and rates of adverse events were similar (14% in the treatment group vs 18% in the placebo group; p = 0.30).In this placebo-controlled randomized clinical trial, we found no effect of aminophylline to prevent acute kidney injury in children recovering from cardiac surgery performed with cardiopulmonary bypass. Future study of preoperative aminophylline administration to prevent acute kidney injury may be warranted.

  View details for DOI 10.1097/PCC.0000000000000612

  View details for PubMedID 26669642

• Utilizing electronic health records to predict acute kidney injury risk and outcomes: workgroup statements from the 15(th) ADQI Consensus Conference. Canadian journal of kidney health and disease Sutherland, S. M., Chawla, L. S., Kane-Gill, S. L., Hsu, R. K., Kramer, A. A., Goldstein, S. L., Kellum, J. A., Ronco, C., Bagshaw, S. M. 2016; 3: 11-?

  Abstract

  The data contained within the electronic health record (EHR) is "big" from the standpoint of volume, velocity, and variety. These circumstances and the pervasive trend towards EHR adoption have sparked interest in applying big data predictive analytic techniques to EHR data. Acute kidney injury (AKI) is a condition well suited to prediction and risk forecasting; not only does the consensus definition for AKI allow temporal anchoring of events, but no treatments exist once AKI develops, underscoring the importance of early identification and prevention. The Acute Dialysis Quality Initiative (ADQI) convened a group of key opinion leaders and stakeholders to consider how best to approach AKI research and care in the "Big Data" era. This manuscript addresses the core elements of AKI risk prediction and outlines potential pathways and processes. We describe AKI prediction targets, feature selection, model development, and data display.

  View details for DOI 10.1186/s40697-016-0099-4

  View details for PubMedID 26925247

  View details for PubMedCentralID PMC4768420

• A Hyperpigmented Reticular Rash in a Patient on Peritoneal Dialysis. Peritoneal dialysis international South, A. M., Crispin, M. K., Marqueling, A. L., Sutherland, S. M. 2016; 36 (6): 699-700

  Abstract

  Chronically ill patients often develop uncommon exam findings. A 16-year-old female with end-stage renal disease secondary to immune complex-mediated glomerulonephritis on peritoneal dialysis (PD) developed a pruritic, hyperpigmented reticular rash on her abdomen, sparing the PD catheter insertion site. The rash appeared approximately 6 weeks after initiating PD. She used a heating pad nightly during PD for dialysis drain pain. Testing for systemic and autoimmune disease was negative. She was referred to dermatology, where the diagnosis of erythema ab igne (EAI), a well-described but less well-known hyperpigmented reticular cutaneous eruption caused by chronic exposure to low levels of infrared heat, was confirmed. The eruption is typically painless but is often pruritic. Common sources of heat include fires, stoves, portable heaters, heating pads, and laptop computers. The association between EAI and PD is unknown. Our patient discontinued the heating pad and her rash resolved.

  View details for PubMedID 27903857

• Applications for detection of acute kidney injury using electronic medical records and clinical information systems: workgroup statements from the 15(th) ADQI Consensus Conference. Canadian journal of kidney health and disease James, M. T., Hobson, C. E., Darmon, M., Mohan, S., Hudson, D., Goldstein, S. L., Ronco, C., Kellum, J. A., Bagshaw, S. M. 2016; 3: 9-?

  Abstract

  Electronic medical records and clinical information systems are increasingly used in hospitals and can be leveraged to improve recognition and care for acute kidney injury. This Acute Dialysis Quality Initiative (ADQI) workgroup was convened to develop consensus around principles for the design of automated AKI detection systems to produce real-time AKI alerts using electronic systems. AKI alerts were recognized by the workgroup as an opportunity to prompt earlier clinical evaluation, further testing and ultimately intervention, rather than as a diagnostic label. Workgroup members agreed with designing AKI alert systems to align with the existing KDIGO classification system, but recommended future work to further refine the appropriateness of AKI alerts and to link these alerts to actionable recommendations for AKI care. The consensus statements developed in this review can be used as a roadmap for development of future electronic applications for automated detection and reporting of AKI.

  View details for DOI 10.1186/s40697-016-0100-2

  View details for PubMedID 26925245

• Acute kidney injury in the era of big data: the 15(th) Consensus Conference of the Acute Dialysis Quality Initiative (ADQI). Canadian journal of kidney health and disease Bagshaw, S. M., Goldstein, S. L., Ronco, C., Kellum, J. A. 2016; 3: 5-?

  Abstract

  The world is immersed in "big data". Big data has brought about radical innovations in the methods used to capture, transfer, store and analyze the vast quantities of data generated every minute of every day. At the same time; however, it has also become far easier and relatively inexpensive to do so. Rapidly transforming, integrating and applying this large volume and variety of data are what underlie the future of big data. The application of big data and predictive analytics in healthcare holds great promise to drive innovation, reduce cost and improve patient outcomes, health services operations and value. Acute kidney injury (AKI) may be an ideal syndrome from which various dimensions and applications built within the context of big data may influence the structure of services delivery, care processes and outcomes for patients. The use of innovative forms of "information technology" was originally identified by the Acute Dialysis Quality Initiative (ADQI) in 2002 as a core concept in need of attention to improve the care and outcomes for patients with AKI. For this 15(th) ADQI consensus meeting held on September 6-8, 2015 in Banff, Canada, five topics focused on AKI and acute renal replacement therapy were developed where extensive applications for use of big data were recognized and/or foreseen. In this series of articles in the Canadian Journal of Kidney Health and Disease, we describe the output from these discussions.

  View details for DOI 10.1186/s40697-016-0103-z

  View details for PubMedID 26925244

• Establishing a continuum of acute kidney injury - tracing AKI using data source linkage and long-term follow-up: Workgroup Statements from the 15th ADQI Consensus Conference. Canadian journal of kidney health and disease Mehta, R., Bihorac, A., Selby, N. M., Quan, H., Goldstein, S. L., Kellum, J. A., Ronco, C., Bagshaw, S. M. 2016; 3: 13-?

  Abstract

  Acute kidney injury (AKI) is independently associated with the development of chronic kidney disease, endstage kidney disease and increased all-cause and cardiovascular-specific mortality. The severity of the renal insult and the development of multiple AKI episodes increase the risk of occurrence of these outcomes. Despite these long-term effects, only a minority of patients receive nephrologist follow up after an episode of AKI; those that do may have improved outcomes. Furthermore, relatively simple quality improvement strategies have the potential to change this status quo.On this background, a working group of the 15(th) Acute Dialysis Quality Initiative (ADQI) conference applied the consensus-building process informed by review of English language articles identified through PubMed search to address questions related to the opportunities, methodological requirements and barriers for longitudinal follow-up of patients with AKI in the era of electronic health records and Big Data.Four consensus statements answering the key questions identified by the working group are developed.We have identified minimal data elements and potential data sources necessary to trace the natural history of patients from onset of AKI to long-term outcome. Minimum infrastructure and key barriers to achieving these goals are outlined together with proposed solutions.

  View details for DOI 10.1186/s40697-016-0102-0

  View details for PubMedID 26925249

• Impact of electronic-alerting of acute kidney injury: workgroup statements from the 15(th) ADQI Consensus Conference. Canadian journal of kidney health and disease Hoste, E. A., Kashani, K., Gibney, N., Wilson, F. P., Ronco, C., Goldstein, S. L., Kellum, J. A., Bagshaw, S. M. 2016; 3: 10-?

  Abstract

  Among hospitalized patients, acute kidney injury is common and associated with significant morbidity and risk for mortality. The use of electronic health records (EHR) for prediction and detection of this important clinical syndrome has grown in the past decade. The steering committee of the 15(th) Acute Dialysis Quality Initiative (ADQI) conference dedicated a workgroup with the task of identifying elements that may impact the course of events following Acute Kidney Injury (AKI) e-alert.Following an extensive, non-systematic literature search, we used a modified Delphi process to reach consensus regarding several aspects of the utilization of AKI e-alerts.Topics discussed in this workgroup included progress in evidence base practices, the characteristics of an optimal e-alert, the measures of efficacy and effectiveness, and finally what responses would be considered best practices following AKI e-alerts. Authors concluded that the current evidence for e-alert system efficacy, although growing, remains insufficient. Technology and human-related factors were found to be crucial elements of any future investigation or implementation of such tools. The group also concluded that implementation of such systems should not be done without a vigorous plan to evaluate the efficacy and effectiveness of e-alerts. Efficacy and effectiveness of e-alerts should be measured by context-specific process and patient outcomes. Finally, the group made several suggestions regarding the clinical decision support that should be considered following successful e-alert implementation.This paper reflects the findings of a non-systematic review and expert opinion.We recommend implementation of the findings of this workgroup report for use of AKI e-alerts.

  View details for DOI 10.1186/s40697-016-0101-1

  View details for PubMedID 26925246

• Perioperative fluid management and postoperative hyponatremia in children PEDIATRIC NEPHROLOGY Oh, G. J., Sutherland, S. M. 2016; 31 (1): 53-60

  Abstract

  Intravenous (IV) fluids are used ubiquitously when children undergo surgical procedures. Until recently, Holliday and Segar's guidelines for calculating maintenance fluids dictated fluid management strategies in postoperative pediatric patients. An increased recognition of hospital-acquired hyponatremia and its associated morbidity has led to a critical re-examination of IV fluid management in this population. Postsurgical patients are at high risk of developing hyponatremia due to the presence of non-osmotic stimuli for antidiuretic hormone release. Recent studies have established that, as they are administered in current practice, hypotonic maintenance fluids are associated with increased rates of hyponatremia. The best available data demonstrate that administration of isotonic fluid reduces hyponatremic risk. In this review, we discuss the collective data available on the subject and offer guidelines for fluid management and therapeutic monitoring.

  View details for DOI 10.1007/s00467-015-3081-y

  View details for Web of Science ID 000365100500005

  View details for PubMedID 25784018

• Optimizing administrative datasets to examine acute kidney injury in the era of big data: workgroup statement from the 15(th) ADQI Consensus Conference. Canadian journal of kidney health and disease Siew, E. D., Basu, R. K., Wunsch, H., Shaw, A. D., Goldstein, S. L., Ronco, C., Kellum, J. A., Bagshaw, S. M. 2016; 3: 12-?

  Abstract

  The purpose of this review is to report how administrative data have been used to study AKI, identify current limitations, and suggest how these data sources might be enhanced to address knowledge gaps in the field.1) To review the existing evidence-base on how AKI is coded across administrative datasets, 2) To identify limitations, gaps in knowledge, and major barriers to scientific progress in AKI related to coding in administrative data, 3) To discuss how administrative data for AKI might be enhanced to enable "communication" and "translation" within and across administrative jurisdictions, and 4) To suggest how administrative databases might be configured to inform 'registry-based' pragmatic studies.Literature review of English language articles through PubMed search for relevant AKI literature focusing on the validation of AKI in administrative data or used administrative data to describe the epidemiology of AKI.Acute Dialysis Quality Initiative (ADQI) Consensus Conference September 6-7(th), 2015, Banff, Canada.Hospitalized patients with AKI.The coding structure for AKI in many administrative datasets limits understanding of true disease burden (especially less severe AKI), its temporal trends, and clinical phenotyping. Important opportunities exist to improve the quality and coding of AKI data to better address critical knowledge gaps in AKI and improve care.A modified Delphi consensus building process consisting of review of the literature and summary statements were developed through a series of alternating breakout and plenary sessions.Administrative codes for AKI are limited by poor sensitivity, lack of standardization to classify severity, and poor contextual phenotyping. These limitations are further hampered by reduced awareness of AKI among providers and the subjective nature of reporting. While an idealized definition of AKI may be difficult to implement, improving standardization of reporting by using laboratory-based definitions and providing complementary information on the context in which AKI occurs are possible. Administrative databases may also help enhance the conduct of and inform clinical or registry-based pragmatic studies.Data sources largely restricted to North American and Europe.Administrative data are rapidly growing and evolving, and represent an unprecedented opportunity to address knowledge gaps in AKI. Progress will require continued efforts to improve awareness of the impact of AKI on public health, engage key stakeholders, and develop tangible strategies to reconfigure infrastructure to improve the reporting and phenotyping of AKI. WHY IS THIS REVIEW IMPORTANT?: Rapid growth in the size and availability of administrative data has enhanced the clinical study of acute kidney injury (AKI). However, significant limitations exist in coding that hinder our ability to better understand its epidemiology and address knowledge gaps. The following consensus-based review discusses how administrative data have been used to study AKI, identify current limitations, and suggest how these data sources might be enhanced to improve the future study of this disease. WHAT ARE THE KEY MESSAGES?: The current coding structure of administrative data is hindered by a lack of sensitivity, standardization to properly classify severity, and limited clinical phenotyping. These limitations combined with reduced awareness of AKI and the subjective nature of reporting limit understanding of disease burden across settings and time periods. As administrative data become more sophisticated and complex, important opportunities to employ more objective criteria to diagnose and stage AKI as well as improve contextual phenotyping exist that can help address knowledge gaps and improve care.

  View details for DOI 10.1186/s40697-016-0098-5

  View details for PubMedID 26925248

• Exploring Value in Congenital Heart Disease: An Evaluation of Inpatient Admissions. Congenital heart disease Shin, A. Y., Hu, Z., Jin, B., Lal, S., Rosenthal, D. N., Efron, B., Sharek, P. J., Sutherland, S. M., Cohen, H. J., McElhinney, D. B., Roth, S. J., Ling, X. B. 2015; 10 (6): E278-87

  Abstract

  Understanding value provides an important context for improvement. However, most health care models fail to measure value. Our objective was to categorize inpatient encounters within an academic congenital heart program based on clinical outcome and the cost to achieve the outcome (value). We aimed to describe clinical and nonclinical features associated with value.We defined hospital encounters based on outcome per resource utilized. We performed principal component and cluster analysis to classify encounters based on mortality, length of stay, hospital cost and revenue into six classes. We used nearest shrunken centroid to identify discriminant features associated with the cluster-derived classes. These features underwent hierarchical clustering and multivariate analysis to identify features associated with each class.We analyzed all patients admitted to an academic congenital heart program between September 1, 2009, and December 31, 2012.A total of 2658 encounters occurred during the study period. Six classes were categorized by value. Low-performing value classes were associated with greater institutional reward; however, encounters with higher-performing value were associated with a loss in profitability. Encounters that included insertion of a pediatric ventricular assist device (log OR 2.5 [95% CI, 1.78 to 3.43]) and acquisition of a hospital-acquired infection (log OR 1.42 [95% CI, 0.99 to 1.87]) were risk factors for inferior health care value.Among the patients in our study, institutional reward was not associated with value. We describe a framework to target quality improvement and resource management efforts that can benefit patients, institutions, and payers alike.

  View details for DOI 10.1111/chd.12290

  View details for PubMedID 26219731

• CRIT-LINE: a noninvasive tool to monitor hemoglobin levels in pediatric hemodialysis patients PEDIATRIC NEPHROLOGY Garro, R., Sutherland, S., Bayes, L., Alexander, S., Wong, C. 2015; 30 (6): 991-998

  Abstract

  The national average for achieving the KDOQI-recommended hemoglobin (Hgb) target level of 11-12 g/dL is low with the current anemia management protocol of measuring Hgb levels every 2-4 weeks to guide intervention. The objective of this study was to correlate initial Hgb readings from the CRIT-LINE monitor with actual serum Hgb levels in pediatric patients on hemodialysis (HD).Data were collected from pediatric HD patients who had Hgb tests ordered for routine and/or clinical reasons. Hgb concentrations were read with the CRIT-LINE after 0.5 or 1 L of blood had been processed by HD in patients with a body weight of ≤20 or >20 kg, respectively. Ultrafiltration was kept at a minimum until the CRIT-LINE Hgb was read.In total, 217 Hgb readings from 23 HD patients were analyzed. Results showed a statistically significant correlation between CRIT-LINE readings and laboratory Hgb measurements (r = 0.94, p < 0.0001) using Pearson correlation coefficients for well-distributed data. The mean Hgb levels measured by CRIT-LINE and the laboratory were 11.12 ± 1.63 and 11.31 ± 1.69 g/dL, respectively.The CRIT-LINE monitor is an accurate instrument for monitoring Hgb levels in HD patients. Further studies will be needed to evaluate whether using CRIT-LINE Hgb levels to guide anemia management will improve the percentage of children with Hgb levels within target.

  View details for DOI 10.1007/s00467-014-2986-1

  View details for Web of Science ID 000353296700016

  View details for PubMedID 25854612

• 44-h ambulatory blood pressure monitoring: revealing the true burden of hypertension in pediatric hemodialysis patients. Pediatric nephrology Haskin, O., Wong, C. J., McCabe, L., Begin, B., Sutherland, S. M., Chaudhuri, A. 2015; 30 (4): 653-660

  Abstract

  The blood pressure (BP) burden is high in pediatric hemodialysis (HD) patients and adversely affects prognosis. The aim of this study was to examine whether 44-h ambulatory BP monitoring (ABPM) provides additional relevant BP data compared with 24-h ABPM.ABPM was initiated at the end of the mid-week dialysis run in 13 stable pediatric HD patients and continued until the next run for 44 h. Day 1 was defined as the initial 24-h ABPM and Day 2 as the time period after that until the next dialysis run. All patients had an echocardiogram to calculate the left ventricular mass index (LVMI).A higher percentage of patients were diagnosed with hypertension from the 44-h ABPM than from the 24-h ABPM. All BP indexes and loads (except nighttime diastolic load) were significantly higher on Day 2 than on Day 1. Patients with BP loads of ≥25 % on 44-h ABPM had significantly higher LVMI than those patients with normal BP loads. No such association was found with 24-h ABPM and LVMI. Higher interdialytic weight gain was associated with higher Day-2 nighttime systolic BP load.The 44-h ABPM provides more information than the 24-h ABPM in terms of diagnosing and assessing the true burden of hypertension in pediatric HD patients. Elevated BP loads from 44-h ABPM correlate with a higher LVMI on the echocardiogram.

  View details for DOI 10.1007/s00467-014-2964-7

  View details for PubMedID 25266709

• AKI in Hospitalized Children: Comparing the pRIFLE, AKIN, and KDIGO Definitions CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Sutherland, S. M., Byrnes, J. J., Kothari, M., Longhurst, C. A., Dutta, S., Garcia, P., Goldstein, S. L. 2015; 10 (4): 554-561

  Abstract

  Although several standardized definitions for AKI have been developed, no consensus exists regarding which to use in children. This study applied the Pediatric RIFLE (pRIFLE), AKI Network (AKIN), and Kidney Disease Improving Global Outcomes (KDIGO) criteria to an anonymized cohort of hospitalizations extracted from the electronic medical record to compare AKI incidence and outcomes in intensive care unit (ICU) and non-ICU pediatric populations.Observational, electronic medical record-enabled study of 14,795 hospitalizations at the Lucile Packard Children's Hospital between 2006 and 2010. AKI and AKI severity stage were defined by the pRIFLE, AKIN, and KDIGO definitions according to creatinine change criteria; urine output criteria were not used. The incidences of AKI and each AKI stage were calculated for each classification system. All-cause, in-hospital mortality and total hospital length of stay (LOS) were compared at each subsequent AKI stage by Fisher exact and Kolmogorov-Smirnov tests, respectively.AKI incidences across the cohort according to pRIFLE, AKIN, and KDIGO were 51.1%, 37.3%, and 40.3%. Mortality was higher among patients with AKI across all definitions (pRIFLE, 2.3%; AKIN, 2.7%; KDIGO, 2.5%; P<0.001 versus no AKI [0.8%-1.0%]). Within the ICU, pRIFLE, AKIN, and KDIGO demonstrated progressively higher mortality at each AKI severity stage; AKI was not associated with mortality outside the ICU by any definition. Both in and outside the ICU, AKI was associated with significantly higher LOS at each AKI severity stage across all three definitions (P<0.001). Definitions resulted in differences in diagnosis and staging of AKI; staging agreement ranged from 76.7% to 92.5%.Application of the three definitions led to differences in AKI incidence and staging. AKI was associated with greater mortality and LOS in the ICU and greater LOS outside the ICU. All three definitions demonstrated excellent interstage discrimination. While each definition offers advantages, these results underscore the need to adopt a single, universal AKI definition.

  View details for DOI 10.2215/CJN.01900214

  View details for Web of Science ID 000352463400005

  View details for PubMedID 25649155

• Utility of Clinical Biomarkers to Predict Central Line-associated Bloodstream Infections After Congenital Heart Surgery. Pediatric infectious disease journal Shin, A. Y., Jin, B., Hao, S., Hu, Z., Sutherland, S., McCammond, A., Axelrod, D., Sharek, P., Roth, S. J., Ling, X. B. 2015; 34 (3): 251-254

  Abstract

  Central line associated bloodstream infections is an important contributor of morbidity and mortality in children recovering from congenital heart surgery. The reliability of commonly used biomarkers to differentiate these patients have not been specifically studied.This was a retrospective cohort study in a university-affiliated children's hospital examining all patients with congenital or acquired heart disease admitted to the cardiovascular intensive care unit following cardiac surgery who underwent evaluation for a catheter-associated bloodstream infection.Among 1260 cardiac surgeries performed, 451 encounters underwent an infection evaluation post-operatively. Twenty-five instances of CLABSI and 227 instances of a negative infection evaluation were the subject of analysis. Patients with CLABSI tended to be younger (1.34 vs 4.56 years, p = 0.011) and underwent more complex surgery (RACHS-1 score 3.79 vs 3.04, p = 0.039). The two groups were indistinguishable in WBC, PMNs and band count at the time of their presentation. On multivariate analysis, CLABSI was associated with fever (adjusted OR 4.78; 95% CI, 1.6 to 5.8) and elevated CRP (adjusted OR 1.28; 95% CI, 1.09 to 1.68) after adjusting for differences between the two groups. Receiver operating characteristic analysis demonstrated the discriminatory power of both fever and CRP (area under curve 0.7247, 95% CI, 0.42 to 0.74 and 0.58, 95% CI 0.4208 to 0.7408). We calculated multilevel likelihood ratios for a spectrum of temperature and CRP values.We found commonly used serum biomarkers such as fever and CRP not to be helpful discriminators in patients following congenital heart surgery.

  View details for DOI 10.1097/INF.0000000000000553

  View details for PubMedID 25232780

• Assessment of Worldwide Acute Kidney Injury, Renal Angina and Epidemiology in Critically Ill Children (AWARE): study protocol for a prospective observational study BMC NEPHROLOGY Basu, R. K., Kaddourah, A., Terrell, T., Mottes, T., Arnold, P., Jacobs, J., Andringa, J., Goldstein, S. L. 2015; 16

  Abstract

  Acute kidney injury (AKI) is associated with poor outcome in critically ill children. While data extracted from retrospective study of pediatric populations demonstrate a high incidence of AKI, the literature lacks focused and comprehensive multicenter studies describing AKI risk factors, epidemiology, and outcome. Additionally, very few pediatric studies have examined novel urinary biomarkers outside of the cardiopulmonary bypass population.This is a prospective observational study. We anticipate collecting data on over 5000 critically ill children admitted to 31 pediatric intensive care units (PICUs) across the world during the calendar year of 2014. Data will be collected for seven days on all children older than 90 days and younger than 25 years without baseline stage 5 chronic kidney disease, chronic renal replacement therapy, and outside of 90 days of a kidney transplant or from surgical correction of congenital heart disease. Data to be collected includes demographic information, admission diagnoses and co-morbidities, and details on fluid and vasoactive resuscitation used. The renal angina index will be calculated integrating risk factors and early changes in serum creatinine and fluid overload. On days 2-7, all hemodynamic and pertinent laboratory values will be captured focusing on AKI pertinent values. Daily calculated values will include % fluid overload, fluid corrected creatinine, and KDIGO AKI stage. Urine will be captured twice daily for biomarker analysis on Days 0-3 of admission. Biomarkers to be measured include neutrophil gelatinase lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (l-FABP), and interleukin-18 (IL-18). The primary outcome to be quantified is incidence rate of severe AKI on Day 3 (Day 3-AKI). Prediction of Day 3-AKI by the RAI and after incorporation of biomarkers with RAI will be analyzed.The Assessment of Worldwide Acute Kidney Injury, Renal Angina and Epidemiology (AWARE) study, creates the first prospective international pediatric all cause AKI data warehouse and biologic sample repository, providing a broad and invaluable resource for critical care nephrologists seeking to study risk factors, prediction, identification, and treatment options for a disease syndrome with high associated morbidity affecting a significant proportion of hospitalized children.ClinicalTrials.gov: NCT01987921.

  View details for DOI 10.1186/s12882-015-0016-6

  View details for Web of Science ID 000350789800001

  View details for PubMedID 25882434

• The Prospective Pediatric Continuous Renal Replacement Therapy (ppCRRT) Registry: a critical appraisal PEDIATRIC NEPHROLOGY Sutherland, S. M., Goldstein, S. L., Alexander, S. R. 2014; 29 (11): 2069-2076

  Abstract

  Continuous renal replacement therapy (CRRT), which provides gradual, predictable clearance and fluid removal, is commonly used to manage acute kidney injury (AKI) and fluid overload in critically ill children. The Prospective Pediatric CRRT (ppCRRT) Registry, founded in 2001 and comprising 13 pediatric centers in the United States, represents the largest cohort of children receiving CRRT to date. Data from the ppCRRT has been used to describe pediatric CRRT demographics and epidemiology, improve technical aspects of CRRT provision for children, and identify novel or underappreciated risk factors affecting survival. Whereas the registry has successfully answered many questions, a number of questions remain unanswered and new ones have arisen. This article describes the ppCRRT Registry, including its major findings, the lessons learned, and the limitations inherent in its design. Additionally, using the registry as a framework, areas of future study are identified and potential methodologies examined.

  View details for DOI 10.1007/s00467-013-2594-5

  View details for Web of Science ID 000342457700002

• Acute kidney injury in the pediatric cardiac patient PEDIATRIC ANESTHESIA Axelrod, D. M., Sutherland, S. M. 2014; 24 (9): 899-901

  Abstract

  In summary, AKI after pediatric congenital cardiac surgery represents an important diagnostic and therapeutic challenge in the modern day intensive care unit. AKI in the immediate postoperative period not only portends a poor short-term outcome, but also may relate to chronic kidney disease and mortality in the long term. Its association with increased morbidity, cost, and mortality demands the attention of clinicians and researchers. Future studies should employ a standard AKI definition and should focus on both the mitigation and prevention of AKI events.

  View details for DOI 10.1111/pan.12448

  View details for Web of Science ID 000340533400002

  View details for PubMedID 25092446

• Reply: To PMID 23998517. journal of pediatrics Anglemyer, A., Longhurst, C. A., Sutherland, S. M. 2014; 165 (3): 644-645

  View details for DOI 10.1016/j.jpeds.2014.05.055

  View details for PubMedID 25015572

• Whole-body single-frequency bioimpedance analysis in pediatric hemodialysis patients PEDIATRIC NEPHROLOGY Oh, G., Wong, C., Begin, B., Salsbery, K., Sutherland, S., Chaudhuri, A. 2014; 29 (8): 1417-1423

  Abstract

  We hypothesized that the percent change in resistance (%RΔ) from bioimpedance analysis (BIA) measurements during hemodialysis (HD) can provide information on pediatric HD patients' hydration status.Whole-body single-frequency BIA measurements were obtained before HD, each hour on HD, and after HD during two HD sessions. Pre-and post-HD weights, blood pressures, Crit-Line® measurements, and intradialytic symptoms were collected on the day of the BIA measurements.One hundred and thirty BIA measurements were obtained from 14 HD patients. The group was 43 % girls, and the mean age was 13.2 ± 4.4 years. Percent change in resistance was 13.5 ± 10.8 % at the end of HD; %RΔ correlated with percent body weight change (%BWΔ) following HD (r = -0.83, P < 0.01), as well as with percent blood volume change (%BVΔ) (r = -0.79, P < 0.01). The %RΔ was similar between patients with and without hypertension immediately before HD and was greater in those with intradialytic symptoms (19.1 ± 7.7 %) than in those without (9.9 ± 11.2 %) (P = 0.02). Patients with left ventricular hypertrophy (LVH) had lower %RΔ (7.2 ± 9.7 %) than those without (19.5 ± 7.7 %) (P = 0.03). Left ventricular mass index (LVMI) also correlated strongly with %RΔ (r = -0.79, P = 0.004) and %BWΔ (r = 0.82, P = 0.002).Our study showed that %RΔ strongly correlates with %BWΔ and %BVΔ and that %RΔ also correlated with intradialytic symptoms and LVMI.

  View details for DOI 10.1007/s00467-014-2778-7

  View details for Web of Science ID 000338700400017

• Whole-body single-frequency bioimpedance analysis in pediatric hemodialysis patients. Pediatric nephrology (Berlin, Germany) Oh, G., Wong, C., Begin, B., Salsbery, K., Sutherland, S., Chaudhuri, A. 2014

  Abstract

  We hypothesized that the percent change in resistance (%RΔ) from bioimpedance analysis (BIA) measurements during hemodialysis (HD) can provide information on pediatric HD patients' hydration status.Whole-body single-frequency BIA measurements were obtained before HD, each hour on HD, and after HD during two HD sessions. Pre-and post-HD weights, blood pressures, Crit-Line® measurements, and intradialytic symptoms were collected on the day of the BIA measurements.One hundred and thirty BIA measurements were obtained from 14 HD patients. The group was 43 % girls, and the mean age was 13.2 ± 4.4 years. Percent change in resistance was 13.5 ± 10.8 % at the end of HD; %RΔ correlated with percent body weight change (%BWΔ) following HD (r = -0.83, P < 0.01), as well as with percent blood volume change (%BVΔ) (r = -0.79, P < 0.01). The %RΔ was similar between patients with and without hypertension immediately before HD and was greater in those with intradialytic symptoms (19.1 ± 7.7 %) than in those without (9.9 ± 11.2 %) (P = 0.02). Patients with left ventricular hypertrophy (LVH) had lower %RΔ (7.2 ± 9.7 %) than those without (19.5 ± 7.7 %) (P = 0.03). Left ventricular mass index (LVMI) also correlated strongly with %RΔ (r = -0.79, P = 0.004) and %BWΔ (r = 0.82, P = 0.002).Our study showed that %RΔ strongly correlates with %BWΔ and %BVΔ and that %RΔ also correlated with intradialytic symptoms and LVMI.

  View details for DOI 10.1007/s00467-014-2778-7

  View details for PubMedID 24570069

• Initial Experience Using Aminophylline to Improve Renal Dysfunction in the Pediatric Cardiovascular ICU PEDIATRIC CRITICAL CARE MEDICINE Axelrod, D. M., Anglemyer, A. T., Sherman-Levine, S. F., Zhu, A., Grimm, P. C., Roth, S. J., Sutherland, S. M. 2014; 15 (1): 21-27

  Abstract

  To determine if aminophylline administration is associated with improved creatinine clearance and greater urine output in children with acute kidney injury in the cardiovascular ICU.Single-center retrospective cohort study.Pediatric cardiovascular ICU, university-affiliated children's hospital.Children with congenital or acquired heart disease in the cardiovascular ICU who received aminophylline to treat oliguric acute kidney injury and fluid overload.Patients received aminophylline after consultation with a pediatric nephrologist. Data were collected retrospectively over 7 days to assess if aminophylline was associated with improvement in creatinine clearance, urine output, and fluid overload.Thirty-one patients received 52 aminophylline courses. Over the 7-day study period, serum creatinine decreased from a mean of 1.13 ± 0.91 to 0.87 ± 0.83 mg/dL (-0.05 mg/dL/d, p < 0.001). A concomitant increase was seen in estimated glomerular filtration rate from a mean of 50.0 ± 30.0 to 70.6 ± 58.1 mL/min/1.73 m (+3.66 mL/min/1.73 m/d, p < 0.001). Average daily urine output increased by 0.22 mL/kg/hr (p < 0.001), and fluid overload decreased on average by 0.42% per day in the 7-day study period (p = 0.005). Although mean furosemide dose increased slightly (0.12 mg/kg/d, p = 0.01), hydrochlorothiazide dosing did not significantly change over the study period. There were no complications related to aminophylline administration.Our study suggests that aminophylline therapy may be associated with significantly improved renal excretory function and may augment urine output in children who experience oliguric acute kidney injury in the cardiovascular ICU. Additionally, we did not identify any aminophylline-related side effects in this high-risk cardiac population. Future prospective studies are necessary to confirm the safety profile and to ensure that the beneficial effects are independent of other clinical interventions.

  View details for DOI 10.1097/01.pcc.0000436473.12082.2f

  View details for PubMedID 24212284

• Association between Maintenance Fluid Tonicity and Hospital-Acquired Hyponatremia. journal of pediatrics Carandang, F., Anglemyer, A., Longhurst, C. A., Krishnan, G., Alexander, S. R., Kahana, M., Sutherland, S. M. 2013; 163 (6): 1646-1651

  Abstract

  To evaluate whether the administration of hypotonic fluids compared with isotonic fluids is associated with a greater risk for hyponatremia in hospitalized children.Informatics-enabled cohort study of all hospitalizations at Lucile Packard Children's Hospital between April 2009 and March 2011. Extraction and analysis of electronic medical record data identified normonatremic hospitalized children who received either hypotonic or isotonic intravenous maintenance fluids upon admission. The primary exposure was the administration of hypotonic maintenance fluids, and the primary outcome was the development of hyponatremia (serum sodium <135 mEq/L).A total of 1048 normonatremic children received either hypotonic (n = 674) or isotonic (n = 374) maintenance fluids upon admission. Hyponatremia developed in 260 (38.6%) children who received hypotonic fluids and 104 (27.8%) of those who received isotonic fluids (unadjusted OR 1.63; 95% CI 1.24-2.15, P < .001). After we controlled for intergroup differences and potential confounders, patients receiving hypotonic fluids remained more likely to develop hyponatremia (aOR 1.37, 95% CI 1.03-1.84). Multivariable analysis identified additional factors associated with the development of hyponatremia, including surgical admission (aOR 1.44, 95% CI 1.09-1.91), cardiac admitting diagnosis (aOR 2.08, 95% CI 1.34-3.20), and hematology/oncology admitting diagnosis (aOR 2.37, 95% CI 1.74-3.25).Hyponatremia was common regardless of maintenance fluid tonicity; however, the administration of hypotonic maintenance fluids compared with isotonic fluids was associated with a greater risk of developing hospital-acquired hyponatremia. Additional clinical characteristics modified the hyponatremic effect of hypotonic fluid, and it is possible that optimal maintenance fluid therapy now requires a more individualized approach.

  View details for DOI 10.1016/j.jpeds.2013.07.020

  View details for PubMedID 23998517

• AKI in Hospitalized Children: Epidemiology and Clinical Associations in a National Cohort. Clinical journal of the American Society of Nephrology Sutherland, S. M., Ji, J., Sheikhi, F. H., Widen, E., Tian, L., Alexander, S. R., Ling, X. B. 2013; 8 (10): 1661-1669

  Abstract

  Although AKI is common among hospitalized children, comprehensive epidemiologic data are lacking. This study characterizes pediatric AKI across the United States and identifies AKI risk factors using high-content/high-throughput analytic techniques.For the cross-sectional analysis of the 2009 Kids Inpatient Database, AKI events were identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes. Demographics, incident rates, and outcome data were analyzed and reported for the entire AKI cohort as well as AKI subsets. Statistical learning methods were applied to the highly imbalanced dataset to derive AKI-related risk factors.Of 2,644,263 children, 10,322 children developed AKI (3.9/1000 admissions). Although 19% of the AKI cohort was ≤1 month old, the highest incidence was seen in children 15-18 years old (6.6/1000 admissions); 49% of the AKI cohort was white, but AKI incidence was higher among African Americans (4.5 versus 3.8/1000 admissions). In-hospital mortality among patients with AKI was 15.3% but higher among children ≤1 month old (31.3% versus 10.1%, P<0.001) and children requiring critical care (32.8% versus 9.4%, P<0.001) or dialysis (27.1% versus 14.2%, P<0.001). Shock (odds ratio, 2.15; 95% confidence interval, 1.95 to 2.36), septicemia (odds ratio, 1.37; 95% confidence interval, 1.32 to 1.43), intubation/mechanical ventilation (odds ratio, 1.2; 95% confidence interval, 1.16 to 1.25), circulatory disease (odds ratio, 1.47; 95% confidence interval, 1.32 to 1.65), cardiac congenital anomalies (odds ratio, 1.2; 95% confidence interval, 1.13 to 1.23), and extracorporeal support (odds ratio, 2.58; 95% confidence interval, 2.04 to 3.26) were associated with AKI.AKI occurs in 3.9/1000 at-risk US pediatric hospitalizations. Mortality is highest among neonates and children requiring critical care or dialysis. Identified risk factors suggest that AKI occurs in association with systemic/multiorgan disease more commonly than primary renal disease.

  View details for DOI 10.2215/CJN.00270113

  View details for PubMedID 23833312

• Two-point normalized protein catabolic rate overestimates nPCR in pediatric hemodialysis patients PEDIATRIC NEPHROLOGY Srivaths, P. R., Sutherland, S., Alexander, S., Goldstein, S. L. 2013; 28 (5): 797-801

  Abstract

  Normalized protein catabolic rate (nPCR) calculation depends on estimating the urea generation between consecutive hemodialysis (HD) treatments. Two-point nPCR using blood urea nitrogen (BUN) before and after the same HD treatment has not been validated in pediatric patients, who typically receive a more intense HD dose than adults. This study aimed to compare nPCR calculated with a two-point vs. a three-point nPCR model in pediatric HD patients.Pediatric patients receiving HD at 2 units were enrolled. Three BUN measurements were obtained around a midweek HD treatment: one prior to HD (preBUN1), one 30 s after HD (30sBUN), and one prior to the subsequent HD (preBUN2). The two-point nPCR model was calculated using preBUN1 and 30sBUN and the three-point nPCR model was calculated using preBUN2 and 30sBUN.Seventy-six BUN sets from 35 patients were analyzed. Mean age was 16.4 ± 3.5 years. Mean dry weight was 51.4 ± 17.1 kg. Mean spKt/V was 1.54 ± 0.23. Mean preBUN2 was significantly lower than mean preBUN1 (60.2 ± 18.6 vs. 64.0 ± 18.9 mg/dl, p = 0.0001). nPCR obtained from the three-point model was significantly lower than nPCR obtained from the two-point model (1.07 ± 0.31 vs. 1.17 ± 0.31 g/kg/day, p = 0.00001). Seven of 76 (9.2 %) paired comparisons yielded three-point nPCR <1 vs. two-point nPCR >1.Our data show that in pediatric patients receiving HD, the ((1) two-point and three-point models lead to significantly different nPCRs, and (2) inaccurate protein intake assessment may result from reliance on a two-point model for nPCR estimates.

  View details for DOI 10.1007/s00467-012-2371-x

  View details for Web of Science ID 000316571400014

  View details for PubMedID 23212562

• Continuous renal replacement therapy in children PEDIATRIC NEPHROLOGY Sutherland, S. M., Alexander, S. R. 2012; 27 (11): 2007-2016

  Abstract

  Over the past several decades, the epidemiology of acute kidney injury (AKI) in children has changed significantly. Pediatric patients with AKI frequently have co-morbid conditions, substantial fluid overload, and marked disease severity. At the same time, continuous renal replacement therapy (CRRT) has become the preferred modality for the management of these patients. This manuscript provides a state-of-the-art review of the technical aspects of pediatric CRRT and examines the most recent data regarding CRRT indications, timing of initiation, dosing, and outcomes in critically ill children.

  View details for DOI 10.1007/s00467-011-2080-x

  View details for Web of Science ID 000309342000002

  View details for PubMedID 22366896

• Hypertension Screening During Ambulatory Pediatric Visits in the United States, 2000-2009 PEDIATRICS Shapiro, D. J., Hersh, A. L., Cabana, M. D., Sutherland, S. M., Patel, A. I. 2012; 130 (4): 604-610

  Abstract

  Hypertension occurs in 2% to 5% of children in the United States, and its prevalence has increased during the obesity epidemic. There is no consensus among professional organizations about how frequently blood pressure should be measured in children >3 years old. The purpose of this study was to estimate the frequency of hypertension screening during ambulatory pediatric visits in the United States and to determine patient- and provider-level factors associated with screening during visits specifically for preventive care.We analyzed data from a nationally representative sample of ambulatory visits by using the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey from 2000 through 2009. In the subset of visits involving patients aged 3 to 18 years, we estimated the frequency of screening during all visits, preventive visits, and preventive visits in which overweight/obesity was diagnosed. We used multivariable logistic regression to identify patient- and provider-level factors associated with screening.Hypertension screening occurred during 35% of ambulatory pediatric visits, 67% of preventive visits, and 84% of preventive visits in which overweight/obesity was diagnosed. Between 2000 and 2009, the frequency of screening increased in all visits and in preventive visits. Factors independently associated with screening included older age and overweight/obesity diagnosis.Providers do not measure blood pressure in two-thirds of pediatric visits and one-third of pediatric preventive visits. Providers may understand the importance of screening among overweight/obese children; however, efforts to encourage routine screening, particularly in young children, may be needed.

  View details for DOI 10.1542/peds.2011-3888

  View details for Web of Science ID 000309412100043

  View details for PubMedID 22987883

• Rituximab treatment for recurrence of nephrotic syndrome in a pediatric patient after renal transplantation for congenital nephrotic syndrome of Finnish type PEDIATRIC TRANSPLANTATION Chaudhuri, A., Kambham, N., Sutherland, S., Grimm, P., Alexander, S., Concepcion, W., Sarwal, M., Wong, C. 2012; 16 (5): E183-E187

  Abstract

  Congenital nephrotic syndrome (CNS) of the Finnish type due to mutation in the NPHS-1 gene results in massive proteinuria due to structural abnormality in the glomerular slit diaphragm, and is usually refractory to immunosuppressive therapy. Patients eventually require bilateral nephrectomy and renal replacement therapy, with transplantation being the ultimate goal. Post-transplant recurrence of nephrotic syndrome occurs in about 25% of children and is thought to be immune-mediated secondary to antibodies formed against the nephrin protein in renal allograft. Conventional therapy with calcineurin inhibitors (CNI), cyclophosphamide and corticosteroids with or without plasmapheresis often fails to achieve remission resulting in graft loss in 12-16%. There is limited experience with use of rituximab (RTX) in pediatric organ transplant recipients. We report the first case of post-transplant recurrence of nephrotic syndrome in a 4-yr-old child with CNS due to NPHS-1 mutation in whom CNI, corticosteroid and cyclophosphamide therapy was unsuccessful, but who achieved remission after depletion of B cells with RTX, associated with a decrease in the level of anti-nephrin antibodies. The child remains in remission 5 yr following treatment. Our experience suggests that activated B cells may play a pivotal role in the recurrence of nephrosis after renal transplantation in children with CNS.

  View details for DOI 10.1111/j.1399-3046.2011.01519.x

  View details for PubMedID 21672106

• Complement-fixing donor-specific antibodies identified by a novel C1q assay are associated with allograft loss PEDIATRIC TRANSPLANTATION Sutherland, S. M., Chen, G., Sequeira, F. A., Lou, C. D., Alexander, S. R., Tyan, D. B. 2012; 16 (1): 12-17

  Abstract

  Long-term outcomes following renal transplantation remain disappointing. Recently, interest has focused on the antibody-mediated component of allograft injury and the deleterious effects of DSA. We applied a novel C1q solid-phase assay in parallel with the standard IgG SAB assay to identify DSA with the potential to activate complement by binding C1q. Among 193 consecutive renal transplants at our center, 19.2% developed de novo DSA following transplantation. Of the patients with DSA, 43% had antibodies that bound C1q in vitro [C1q+ DSA]. Patients with C1q+ DSA were more likely to develop allograft loss than patients with DSA that did not bind C1q (46.7% vs. 15%; p = 0.04); patients with C1q+ DSA were nearly six times more likely to lose their transplant than those with C1q- DSA. Additionally, patients with C1q+ DSA who underwent allograft biopsy were more likely to demonstrate C4d deposition (50% vs. 8%; p = 0.03) and meet criteria for acute rejection (60% vs. 17%; p = 0.02) when compared with patients with DSA that did not bind C1q. These data suggest that DSA with the ability to activate complement, as determined by this novel C1q assay, are associated with greater risk of acute rejection and allograft loss.

  View details for DOI 10.1111/j.1399-3046.2011.01599.x

  View details for Web of Science ID 000299154200010

  View details for PubMedID 22093755

• End-Stage Renal Disease and Cardiomyopathy in Children: Cardiac Effects of Renal Transplantation TRANSPLANTATION Lal, A. K., de Biasi, A. R., Alexander, S., Rosenthal, D. N., Sutherland, S. M. 2012; 93 (2): 182-187

  Abstract

  The occurrence and progression of cardiomyopathy is well known in patients with end-stage renal disease (ESRD). However, the feasibility of renal transplantation in the setting of cardiac dysfunction and the effect of renal transplantation on this progression remain poorly studied in pediatric patients.A single-center, retrospective review of pediatric renal transplants between January 1, 2001, and December 31, 2010, was conducted. Six children with ESRD and severe systolic dysfunction underwent renal transplantation. Clinical data were collected and compared for the pretransplant, peritransplant, and posttransplant periods.Nutritional support, dialysis, and chronic kidney disease and heart failure therapy led to improved cardiac function before transplantation (ejection fraction 28.8%±9.6% vs. 44.4%±11.5%; fractional shortening 12.7%±5.1% vs. 23.6%±6.2%); however, normal systolic function was not achieved before transplantation in any patient. After transplantation, two patients had normalization of systolic function by hospital discharge, while the systolic function of the remaining four patients normalized during the first posttransplant year. Mean ejection fraction 1 year posttransplant was 22 units greater than before transplant. All patients experienced excellent allograft function in the peritransplant period. Mean estimated creatinine clearance 1 year posttransplant was 93.2±33.3 mL/min/1.73 m(2).Renal transplantation can be performed safely in children with ESRD and severe systolic dysfunction. After transplantation, systolic function continues to improve and may reach normal levels during the first posttransplant year. The presence of severe systolic dysfunction in pediatric dialysis patients should not deter referral for renal transplantation.

  View details for DOI 10.1097/TP.0b013e31823be7f8

  View details for PubMedID 22146314

• Evidence-Based Medicine in the EMR Era NEW ENGLAND JOURNAL OF MEDICINE Frankovich, J., Longhurst, C. A., Sutherland, S. M. 2011; 365 (19): 1758-1759

  View details for DOI 10.1056/NEJMp1108726

  View details for Web of Science ID 000296762800003

  View details for PubMedID 22047518

• Real-Time, Cohort-Based Clinical Decision Support Using a Novel Bioinformatics Platform to Assess Thrombotic Risk in a Critically Ill Pediatric Patient with Systemic Lupus Erythematosus Frankovich, J. D., Longhurst, C., Sutherland, S., Sandborg, C. I. WILEY-BLACKWELL. 2011: S806

  View details for Web of Science ID 000297621502454

• Disseminated Intravascular Coagulation Due to IgM-Mediated Autoimmune Hemolytic Anemia PEDIATRIC BLOOD & CANCER Bleakly, N. T., Fontaine, M. J., Pate, L. L., Sutherland, S. M., Jeng, M. 2011; 57 (2): 329-331

  Abstract

  Disseminated intravascular coagulation (DIC) due to red cell hemolysis has been previously attributed to transfusion-related hemolytic reactions, but not to autoimmune hemolytic anemia. We report a case of DIC in a child with complement-fixing IgM-mediated cold-agglutinin autoimmune hemolysis, which resulted in arterial thrombosis and gangrene of the upper and lower extremities.

  View details for DOI 10.1002/pbc.23024

  View details for PubMedID 21671368

• Role of Twenty-Four-Hour Ambulatory Blood Pressure Monitoring in Children on Dialysis CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chaudhuri, A., Sutherland, S. M., Begin, B., Salsbery, K., McCabe, L., Potter, D., Alexander, S. R., Wong, C. J. 2011; 6 (4): 870-876

  Abstract

  Pre- or postdialysis BP recordings are imprecise, can be biased, and have poor test-retest reliability in children on dialysis. We aimed to examine the possible differences between pre- and postdialysis BP levels and 24-hour ambulatory BP monitoring (ABPM) in diagnosis of hypertension (HTN).Twenty-four children on dialysis had 24-hour ABPM in the interdialytic period, and values were compared with average pre- and postdialysis systolic BP (SBP) and diastolic BP (DBP) recordings that week. Each patient had an echocardiogram to determine presence of left ventricular hypertrophy (LVH).By ABPM, 8% of patients had white coat HTN and 12% had masked HTN. There was no significant difference in diagnosis of systolic HTN based on ABPM daytime SBP mean or load and postdialysis SBP. However, only 15% of patients had diastolic HTN based on postdialysis measures, whereas 46% of patients had significantly elevated daytime DBP loads and 71% had high nighttime DBP loads on ABPM. Forty-eight percent of patients were SBP nondippers. Children with LVH had higher daytime and nighttime SBP loads, significantly higher daytime and nighttime DBP loads, and lesser degree of nocturnal dipping of SBP compared with those who did not.ABPM is more informative than pre- and postdialysis BPs and improves the predictability of BP as a risk factor for target organ damage. Diagnosis and treatment monitoring of HTN among pediatric dialysis patients is enhanced with addition of ABPM.

  View details for DOI 10.2215/CJN.07960910

  View details for Web of Science ID 000289223600026

  View details for PubMedID 21273374

  View details for PubMedCentralID PMC3069381

• Enterococcal peritonitis in children receiving chronic peritoneal dialysis NEPHROLOGY DIALYSIS TRANSPLANTATION Sutherland, S. M., Alexander, S. R., Feneberg, R., Schaefer, F., Warady, B. A. 2010; 25 (12): 4048-4054

  Abstract

  Peritonitis is a common complication of chronic peritoneal dialysis (CPD) and can be associated with technique failure. Enterococcus is an uncommon peritoneal pathogen in children receiving CPD but represents a potential therapeutic challenge due to its innate resistance to cephalosporins and emerging resistance to glycopeptides.The International Pediatric Peritonitis Registry is a global consortium of 47 paediatric dialysis centres designed to address validation of the International Society for Peritoneal Dialysis paediatric peritonitis treatment guidelines. Between 2001 and 2004, peritonitis episodes were assessed in 392 participating children receiving CPD.Among the 392 patients, 340 episodes of culture-positive peritonitis were evaluated. Twenty of these episodes were due to Enterococcus species (5.9%). There were no clinical characteristics uniquely associated with enterococcal peritonitis at presentation. After 3 days of therapy, 75% of patients were pain free, 95% had decreased effluent cloudiness and 90% were afebrile. Only one patient required a catheter exchange, and all patients experienced full functional recovery. Despite broad in vitro resistance to cephalosporins and 21% resistance to glycopeptides, neither in vitro resistance pattern nor choice of empiric antibiotic regimen affected short- or long-term outcomes.Enterococci are likely responsible for ∼6% of culture-positive peritonitis episodes in children receiving CPD. Although it was not possible to identify patients with enterococcal peritonitis based on presentation, clinical response was not associated with in vitro resistance patterns, and patients who initially received a cephalosporin-based empiric regimen until culture results are available are likely to respond quickly and have full functional recovery.

  View details for DOI 10.1093/ndt/gfq295

  View details for PubMedID 20501457

• Fluid Overload and Mortality in Children Receiving Continuous Renal Replacement Therapy: The Prospective Pediatric Continuous Renal Replacement Therapy Registry AMERICAN JOURNAL OF KIDNEY DISEASES Sutherland, S. M., Zappitelli, M., Alexander, S. R., Chua, A. N., Brophy, P. D., Bunchman, T. E., Hackbarth, R., Somers, M. J., Baum, M., Symons, J. M., Flores, F. X., Benfield, M., Askenazi, D., Chand, D., Fortenberry, J. D., Mahan, J. D., McBryde, K., Blowey, D., Goldstein, S. L. 2010; 55 (2): 316-325

  Abstract

  Critically ill children with hemodynamic instability and acute kidney injury often develop fluid overload. Continuous renal replacement therapy (CRRT) has emerged as a favored modality in the management of such children. This study investigated the association between fluid overload and mortality in children receiving CRRT.Prospective observational study.297 children from 13 centers across the United States participating in the Prospective Pediatric CRRT Registry.Fluid overload from intensive care unit (ICU) admission to CRRT initiation, defined as a percentage equal to (fluid in [L] - fluid out [L])/(ICU admit weight [kg]) x 100%.The primary outcome was survival to pediatric ICU discharge. Data were collected regarding demographics, CRRT parameters, underlying disease process, and severity of illness.153 patients (51.5%) developed < 10% fluid overload, 51 patients (17.2%) developed 10%-20% fluid overload, and 93 patients (31.3%) developed > or = 20% fluid overload. Patients who developed > or = 20% fluid overload at CRRT initiation had significantly higher mortality (61/93; 65.6%) than those who had 10%-20% fluid overload (22/51; 43.1%) and those with < 10% fluid overload (45/153; 29.4%). The association between degree of fluid overload and mortality remained after adjusting for intergroup differences and severity of illness. The adjusted mortality OR was 1.03 (95% CI, 1.01-1.05), suggesting a 3% increase in mortality for each 1% increase in severity of fluid overload. When fluid overload was dichotomized to > or = 20% and < 20%, patients with > or = 20% fluid overload had an adjusted mortality OR of 8.5 (95% CI, 2.8-25.7).This was an observational study; interventions were not standardized. The relationship between fluid overload and mortality remains an association without definitive evidence of causality.Critically ill children who develop greater fluid overload before initiation of CRRT experience higher mortality than those with less fluid overload. Further goal-directed research is required to accurately define optimal fluid overload thresholds for initiation of CRRT.

  View details for DOI 10.1053/j.ajkd.2009.10.048

  View details for Web of Science ID 000274537000021

  View details for PubMedID 20042260

• Protein microarrays identify antibodies to protein kinase C zeta that are associated with a greater risk of allograft loss in pediatric renal transplant recipients KIDNEY INTERNATIONAL Sutherland, S. M., Li, L., Sigdel, T. K., Wadia, P. P., Miklos, D. B., Butte, A. J., Sarwal, M. M. 2009; 76 (12): 1277-1283

  Abstract

  Antibodies to human leukocyte antigens (HLAs) are a risk factor for acute renal allograft rejection and loss. The role of non-HLAs and their significance to allograft rejection have gained recent attention. Here, we applied protein microarray technology, with the capacity to simultaneously identify 5056 potential antigen targets, to assess non-HLA antibody formation in 15 pediatric renal transplant recipients during allograft rejection. Comparison of the pre- and post-transplant serum identified de novo antibodies to 229 non-HLA targets, 36 of which were present in multiple patients at allograft rejection. On the basis of its reactivity, protein kinase Czeta (PKCzeta) was selected for confirmatory testing and clinical study. Immunohistochemical analysis found PKCzeta both within the renal tissue and infiltrating lymphocytes at rejection. Patients who had an elevated anti-PKCzeta titer developed rejection, which was significantly more likely to result in graft loss. The absence of C4d deposition in patients with high anti-PKCzeta titers suggests that it is a marker of severe allograft injury rather than itself being pathogenic. Presumably, critical renal injury and inflammation associated with this rejection subtype lead to the immunological exposure of PKCzeta with resultant antibody formation. Prospective assessment of serum anti-PKCzeta levels at allograft rejection will be needed to confirm these results.

  View details for DOI 10.1038/ki.2009.384

  View details for Web of Science ID 000272230400009

  View details for PubMedID 19812540

• Steroid-Free Immunosuppression in Pediatric Renal Transplantation: Rationale Outcomes Following Conversion to Steroid Based Therapy TRANSPLANTATION Sutherland, S., Li, L., Concepcion, W., Salvatierra, O., Sarwal, M. M. 2009; 87 (11): 1744-1748

  Abstract

  Short-term outcomes using steroid-free immunosuppression after renal transplantation have been promising. No studies have examined the incidence of and reasons for steroid-avoidance protocol failures.We present a single-center analysis of steroid-free immunosuppression failures among 129 pediatric renal transplant recipients with mean follow-up of 5 years. We analyzed causes for failure and examined reasons for conversion to steroid-based therapy. We compared actual patient and allograft survival and allograft function in the cohort of patients who required conversion to steroid-based immunosuppression with that of the cohort maintaining steroid-free immunosuppression.A total of 13.2% (17/129) of patients failed steroid-free immunosuppression. Actual patient survival was equivalent in the two cohorts, 96.4% for the cohort maintaining steroid-free immunosuppression and 94.1% for those requiring conversion. Actual allograft survival was lower in patients requiring conversion to a steroid-based protocol, 76.5% vs. 95.5% (P=0.004). Estimated glomerular filtration rates 12-months and 24-months posttransplant were greater in patients maintaining steroid-free immunosuppression (P=0.003). Most patients (52.9%, 9/17) who broke the steroid-free protocol did so because of refractory acute rejection. The second most common reason was recurrence of glomerulonephritis (GN; 35.3%, 6/17).The failure rate of steroid-free immunosuppression among selective pediatric patients undergoing renal transplantation is low. Patients maintaining steroid-free immunosuppression have better allograft survival and function than those requiring conversion to steroid-based therapy. The most common reasons for failure of steroid-free immunosuppression are recalcitrant or recurrent allograft rejection and recurrent GN; the role of conversion to steroid-based immunosuppression after episodes of acute rejection and recurrent GN requires additional analysis.

  View details for DOI 10.1097/TP.0b013e3181a5df60

  View details for Web of Science ID 000266889900022

  View details for PubMedID 19502970

  View details for PubMedCentralID PMC2758080

• The challenge for the caregiver of the patient with chronic kidney disease NEPHROLOGY DIALYSIS TRANSPLANTATION Gayomali, C., Sutherland, S., Finkelstein, F. O. 2008; 23 (12): 3749-3751

  View details for DOI 10.1093/ndt/gfn577

  View details for Web of Science ID 000261170100005

  View details for PubMedID 19028759

• Combined liver-kidney transplantation in children: Indications and outcome PEDIATRIC TRANSPLANTATION Sutherland, S. M., Alexander, S. R., Sarwal, M. M., Berquist, W. E., Concepcion, W. 2008; 12 (8): 835-846

  Abstract

  Although it remains a relatively infrequent procedure in children, CLKT has become a viable option for a select group of pediatric patients with severe liver and kidney disease. Most are performed for rare primary diseases such as PH1, but a selected few are performed in the setting of concomitant hepatic and renal failure of uncertain etiology and prognosis. This article reviews the indications for and outcomes following CLKT in children. While it focuses on the specific primary diseases which impact liver and kidney function simultaneously, it addresses the indications based on concomitant hepatic and renal failure, such as seen in the hepatorenal syndrome, as well.

  View details for DOI 10.1111/j.1399-3046.2008.01041.x

  View details for Web of Science ID 000260341600004

  View details for PubMedID 19000066

• Identification of non-HLA antigen targets during acute renal allograft rejection using a human protoarray platform 8th American Transplant Congress Sutherland, S., Wadia, P., Miklos, D., Butte, A., Sarwal, M. WILEY-BLACKWELL. 2008: 635–635

  View details for Web of Science ID 000255763202542

• Liposomal amphotericin B associated with severe hyperphosphatemia PEDIATRIC INFECTIOUS DISEASE JOURNAL Sutherland, S. M., Hong, D. K., Balagtas, J., Gutierrez, K., Dvorak, C. C., Sarwal, M. 2008; 27 (1): 77-79

  Abstract

  We report 4 patients who developed hyperphosphatemia while receiving liposomal amphotericin B to treat an invasive fungal infection. Resolution of the hyperphosphatemia occurred after transition to amphotericin B lipid complex. This phenomenon may occur more commonly in patients with mild to moderate renal insufficiency.

  View details for DOI 10.1097/INF.0b013e31815922a3

  View details for PubMedID 18162947

• Three cases of suspected antibody-mediated rejection. Clinical transplants Sutherland, S. M., Sarwal, M. 2006: 473-478

  View details for PubMedID 18365406