Shina Menon

All Publications

• Optimizing kidney health following pediatric liver transplantation: current challenges and future directions. Pediatric nephrology (Berlin, Germany) Ruebner, R. L., Menon, S. 2024

  View details for DOI 10.1007/s00467-024-06606-z

  View details for PubMedID 39585358

  View details for PubMedCentralID 4332846

• The Landscape of Pediatric Acute Care Nephrology Programs: A National Survey from the American Society of Pediatric Nephrology KIDNEY360 Drake, K., Menon, S., Short, K., Plomaritas, K., Crawford, B., Merrill, K., Riley, A., Shih, W., Askenazi, D., Selewski, D., Amer Soc Pediat Nephrology ASPN Acute Care Nephrology 2024; 5 (11): 1713-1717

  View details for DOI 10.34067/KID.0000000593

  View details for Web of Science ID 001361757700017

• Association of delayed cord clamping with acute kidney injury and two-year kidney outcomes in extremely premature neonates: a secondary analysis of the preterm erythropoietin neuroprotection trial (PENUT). Journal of perinatology : official journal of the California Perinatal Association Zapata, H. A., Todurkar, N., Favel, K., Griffin, R. L., Starr, M. C., Charlton, J. R., McAdams, R. M., Askenazi, D., Kulkarni, T., Menon, S., Mammen, C., Harer, M. W. 2024

  Abstract

  BACKGROUND: Delayed cord clamping (DCC) occurs in most preterm births.OBJECTIVE: Evaluate the association of DCC with acute kidney injury (AKI) and two-year kidney outcomes.METHODS: Secondary analysis of the Preterm Erythropoietin Neuroprotection Trial of neonates born 240/7 to 276/7 weeks gestation. AKI and two year kidney outcomes were compared in neonates with DCC (≥30s after delivery) to those with early cord clamping (ECC) (<30s after delivery).RESULTS: The incidence and severity of AKI did not differ between the DCC and ECC groups (aOR 1.17 [95%CI 0.76-1.80]). At two years corrected age, DCC was associated with a 4.5-fold increased adjusted odds of estimated glomerular filtration rate (eGFR) <90mL/min/1.73m2. No significant associations were noted between DCC and albuminuria or elevatedblood pressure.CONCLUSIONS: DCC was not associated with decreased neonatal AKI, but was associated with higher adjusted odds of eGFR <90mL/min/1.73m2 at two years.

  View details for DOI 10.1038/s41372-024-02143-7

  View details for PubMedID 39390245

• Sociodemographic Disparities in Pediatric Acute Kidney Injury-The Right Questions and the Right Definitions. JAMA network open Sanderson, K. R., Menon, S., Jetton, J. G. 2024; 7 (10): e2440907

  View details for DOI 10.1001/jamanetworkopen.2024.40907

  View details for PubMedID 39470643

• Kidney Health Monitoring in Neonatal Intensive Care Unit Graduates: A Modified Delphi Consensus Statement. JAMA network open Starr, M. C., Harer, M. W., Steflik, H. J., Gorga, S., Ambalavanan, N., Beck, T. M., Chaudhry, P. M., Chmielewski, J. L., Defreitas, M. J., Fuhrman, D. Y., Hanna, M., Joseph, C., Kwiatkowski, D. M., Krawczeski, C. D., Liberio, B. M., Menon, S., Mohamed, T. H., Rumpel, J. A., Sanderson, K. R., Schuh, M. P., Segar, J. L., Slagle, C. L., Soranno, D. E., Vuong, K. T., Charlton, J. R., Gist, K. M., Askenazi, D. J., Selewski, D. T. 2024; 7 (9): e2435043

  Abstract

  Kidney disease is common in infants admitted to the neonatal intensive care unit (NICU). Despite the risk of chronic kidney disease (CKD) in infants discharged from the NICU, neither evidence- nor expert-based recommendations exist to guide clinical care after discharge.To develop recommendations for risk stratification and kidney health monitoring among infants after discharge from the NICU.At the National Institute of Health-supported Consensus Workshop to Address Kidney Health in Neonatal Intensive Care Unit Graduates meeting conducted in February 2024, a panel of 51 neonatal nephrology experts focused on 3 at-risk groups: (1) preterm infants, (2) critically ill infants with acute kidney injury (AKI), and (3) infants with critical cardiac disease. Using established modified Delphi processes, workgroups derived consensus recommendations.In this modified Delphi consensus statement, the panel developed 10 consensus recommendations, identified gaps in knowledge, and prioritized areas of future research. Principal suggestions include risk stratification at time of hospital discharge, family and clinician education and counseling for subsequent kidney health follow-up, and blood pressure assessment as part of outpatient care.Preterm infants, critically ill infants with AKI, and infants with critical cardiac disease are at increased risk of CKD. We recommend (1) risk assessment at the time of discharge, (2) clinician and family education, and (3) kidney health assessments based on the degree of risk. Future work should focus on improved risk stratification, identification of early kidney dysfunction, and development of interventions to improve long-term kidney health.

  View details for DOI 10.1001/jamanetworkopen.2024.35043

  View details for PubMedID 39269711

• Acute Renal Replacement Therapy in Pediatric Patients: a National Survey Assessing Programmatic Delivery of Care Selewski, D., Short, K., Plomaritas, K., Crawford, B., Merrill, K., Riley, A., Shih, W., Askenazi, D., Menon, S., Drake, K. SPRINGER. 2024: S139-S140

  View details for Web of Science ID 001331366600232

• Characteristics and outcomes of children ≤ 10 kg receiving continuous kidney replacement therapy: a WE-ROCK study. Pediatric nephrology (Berlin, Germany) Menon, S., Starr, M. C., Zang, H., Collins, M., Damian, M. A., Fuhrman, D., Krallman, K., Soranno, D. E., Webb, T. N., Slagle, C., Joseph, C., Martin, S. D., Mohamed, T., Beebe, M. E., Ricci, Z., Ollberding, N., Selewski, D., Gist, K. M. 2024

  Abstract

  Continuous kidney replacement therapy (CKRT) is often used for acute kidney injury (AKI) or fluid overload (FO) in children ≤ 10 kg. Intensive care unit (ICU) mortality in children ≤ 10 kg reported by the prospective pediatric CRRT (ppCRRT, 2001-2003) registry was 57%. We aimed to evaluate characteristics associated with ICU mortality using a contemporary registry.The Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) registry is a retrospective, multinational, observational study of children and young adults aged 0-25 years receiving CKRT (2015-2021) for AKI or FO. This analysis included patients ≤ 10 kg at hospital admission.ICU mortality and major adverse kidney events at 90 days (MAKE-90) defined as death, persistent kidney dysfunction, or dialysis within 90 days, respectively.A total of 210 patients were included (median age 0.53 years (IQR, 0.1, 0.9)). ICU mortality was 46.5%. MAKE-90 occurred in 150/207 (72%). CKRT was initiated at a median 3 days (IQR 1, 9) after ICU admission and lasted a median 6 days (IQR 3, 16). On multivariable analysis, pediatric logistic organ dysfunction score (PELOD-2) at CKRT initiation was associated with increased odds of ICU mortality (aOR 2.64, 95% CI 1.68-4.16), and increased odds of MAKE-90 (aOR 2.2, 95% CI 1.31-3.69). Absence of comorbidity was associated with lower MAKE-90 (aOR 0.29, 95%CI 0.13-0.65).We report on a contemporary cohort of children ≤ 10 kg treated with CKRT for acute kidney injury and/or fluid overload. ICU mortality is decreased compared to ppCRRT. The extended risk of death and morbidity at 90 days highlights the importance of close follow-up.

  View details for DOI 10.1007/s00467-024-06438-x

  View details for PubMedID 39164502

  View details for PubMedCentralID 5933049

• Derivation and Validation of an Optimal Neutrophil Gelatinase-Associated Lipocalin Cutoff to Predict Stage 2/3 Acute Kidney Injury (AKI) in Critically Ill Children. Kidney international reports Goldstein, S. L., Akcan-Arikan, A., Afonso, N., Askenazi, D. J., Basalely, A. M., Basu, R. K., Beng, H., Fitzgerald, J. C., Gist, K., Kizilbash, S., Kwiatkowski, D., Mastropietro, C. W., Menon, S., SooHoo, M., Traum, A. Z., Bird, C. A. 2024; 9 (8): 2443-2452

  Abstract

  Acute kidney injury (AKI) defined by changes in serum creatinine (SCr), or oliguria is associated with increased morbidity and mortality in children who are critically ill. We derived and validated a clinical cutoff value for urine neutrophil gelatinase-associated lipocalin (NGAL), in a prospective multicenter study of children who were critically ill. We report the clinical performance of urine NGAL (uNGAL) to aid in pediatric AKI risk assessment.Eligible subjects were aged ≥ 90 days to < 22 years, admitted to an intensive care unit (ICU), and had 1 or more of the following: mechanical ventilation, vasoactive medication administration, solid organ or bone marrow transplantation, or hypotension within 24-hours of admission. uNGAL was assessed within 24-hours of admission. The primary outcome was SCr-based stage 2/3 AKI presence at 48- to 72-hours.Twenty-five (12.3%) derivation study patients had stage 2/3 AKI at 48- to 72-hours. uNGAL concentration of 125 ng/ml was the optimal cutoff. Forty-seven (9.1%) validation study patients had stage 2/3 AKI at 48- to 72-hours. The area under the curve of a receiver operator characteristics curve (AUC-ROC) for uNGAL performance was 0.83 (95% confidence interval [CI]: 0.77-0.90). Performance characteristics were sensitivity 72.3% (95% CI: 57.4%-84.4%), specificity 86.3% (95% CI: 82.8%-89.3%), positive predictive value 34.7% (95% CI: 28.5%-41.5%), and negative predictive value 96.9% (95% CI: 95.1%-98.0%).These prospective, pediatric, multicenter studies demonstrate that uNGAL in the first 24-hours performs very well to predict Kidney Disease Improving Global Outcomes (KDIGO) stage 2/3 AKI at 48- to 72-hours into an ICU course. We suggest that a uNGAL cut point of 125 ng/ml can aid in the risk assessment for stage 2/3 AKI persistence or development.

  View details for DOI 10.1016/j.ekir.2024.05.010

  View details for PubMedID 39156146

  View details for PubMedCentralID PMC11328761

• Perinatal risk factors associated with acute kidney injury severity and duration among infants born extremely preterm (Mar, 10.1038/s41390-024-03102-w, 2024) PEDIATRIC RESEARCH Sanderson, K., Griffin, R., Anderson, N., South, A. M., Swanson, J. R., Zappitelli, M., Steflik, H. J., Defreitas, M. J., Charlton, J., Askenazi, D., Neonatal Kidney Collaborative NKC Res Comm 2024: 1096

  View details for DOI 10.1038/s41390-024-03221-4

  View details for Web of Science ID 001272945700001

  View details for PubMedID 39030257

• Responding to the workforce crisis: consensus recommendations from the Second Workforce Summit of the American Society of Pediatric Nephrology. Pediatric nephrology (Berlin, Germany) Soranno, D. E., Amaral, S., Ashoor, I., Atkinson, M. A., Barletta, G. M., Braun, M. C., Carlson, J., Carter, C., Chua, A., Dharnidharka, V. R., Drake, K., Erkan, E., Feig, D., Goldstein, S. L., Hains, D., Harshman, L. A., Ingulli, E., Kula, A. J., Leonard, M., Mannemuddhu, S., Menon, S., Modi, Z. J., Moxey-Mims, M., Nada, A., Norwood, V., Starr, M. C., Verghese, P. S., Weidemann, D., Weinstein, A., Smith, J. 2024

  Abstract

  Pediatric patients with complex medical problems benefit from pediatric sub-specialty care; however, a significant proportion of children live greater than 80 mi. away from pediatric sub-specialty care.To identify current knowledge gaps and outline concrete next steps to make progress on issues that have persistently challenged the pediatric nephrology workforce.Workforce Summit 2.0 employed the round table format and methodology for consensus building using adapted Delphi principles. Content domains were identified via input from the ASPN Workforce Committee, the ASPN's 2023 Strategic Plan survey, the ASPN's Pediatric Nephrology Division Directors survey, and ongoing feedback from ASPN members. Working groups met prior to the Summit to conduct an organized literature review and establish key questions to be addressed. The Summit was held in-person in November 2023. During the Summit, work groups presented their preliminary findings, and the at-large group developed the key action statements and future directions.A holistic appraisal of the effort required to cover inpatient and outpatient sub-specialty care will help define faculty effort and time distribution. Most pediatric nephrologists practice in academic settings, so work beyond clinical care including education, research, advocacy, and administrative/service tasks may form a substantial amount of a faculty member's time and effort. An academic relative value unit (RVU) may assist in creating a more inclusive assessment of their contributions to their academic practice. Pediatric sub-specialties, such as nephrology, contribute to the clinical mission and care of their institutions beyond their direct billable RVUs. Advocacy throughout the field of pediatrics is necessary in order for reimbursement of pediatric sub-specialist care to accurately reflect the time and effort required to address complex care needs. Flexible, individualized training pathways may improve recruitment into sub-specialty fields such as nephrology.The workforce crisis facing the pediatric nephrology field is echoed throughout many pediatric sub-specialties. Efforts to improve recruitment, retention, and reimbursement are necessary to improve the care delivered to pediatric patients.

  View details for DOI 10.1007/s00467-024-06410-9

  View details for PubMedID 38976042

  View details for PubMedCentralID 9346544

• Approaches to neonatal acute kidney injury consultation and follow-up: results of a provider survey. Journal of perinatology : official journal of the California Perinatal Association Feeney, A., Slagle, C. L., Harer, M. W., Charlton, J. R., Mohamed, T., Askenazi, D. J., Menon, S., Selewski, D. T., Starr, M. C. 2024

  View details for DOI 10.1038/s41372-024-02016-z

  View details for PubMedID 38806633

  View details for PubMedCentralID 2755786

• Continuous renal replacement therapy and therapeutic plasma exchange in pediatric liver failure. European journal of pediatrics Jackson, C., Carlin, K., Blondet, N., Jordan, I., Yalon, L., Healey, P. J., Symons, J. M., Menon, S. 2024

  Abstract

  Patients with acute liver failure (ALF) and acute on chronic liver failure (ACLF) have significant morbidity and mortality. They require extracorporeal blood purification modalities like continuous renal replacement therapy (CRRT) and therapeutic plasma exchange (TPE) as a bridge to recovery or liver transplantation. Limited data are available on the outcomes of patients treated with these therapies. This is a retrospective single-center study of 23 patients from 2015 to 2022 with ALF/ACLF who underwent CRRT and TPE. We aimed to describe the clinical characteristics and outcomes of these patients. Median (IQR) age was 0.93 years (0.57, 9.88), range 16 days to 20 years. Ten (43%) had ALF and 13 (57%) ACLF. Most (n = 19, 82%) started CRRT for hyperammonemia and/or hepatic encephalopathy and all received TPE for refractory coagulopathy. CRRT was started at a median of 2 days from ICU admission, and TPE started on the same day in most. The liver transplant was done in 17 (74%), and 2 recovered native liver function. Four patients, all with ACLF, died prior to ICU discharge without a liver transplant. The median peak ammonia pre-CRRT was 131 µmol/L for the whole cohort. The mean (SD) drop in ammonia after 48 h of CRRT was 95.45 (43.72) µmol/L in those who survived and 69.50 (21.70) µmol/L in those who did not (p 0.26). Those who survived had 0 median co-morbidities compared to 2.5 in non-survivors (aOR (95% CI) for mortality risk of 2.5 (1.1-5.7), p 0.028).  Conclusion: In this cohort of 23 pediatric patients with ALF or ACLF who received CRRT and TPE, 83% survived with a liver transplant or recovered with their native liver. Survival was worse in those who had ACLF and those with co-morbid conditions. What is Known: •  Pediatric acute liver failure is associated with high mortality. •  Patients may require extracorporeal liver assist therapies (like CRRT, TPE, MARS, SPAD) to bridge them over to a transplant or recovery of native liver function. What is New: • Standard volume plasma exhange has not been evaluated against high volume plasma exchange for ALF. • The role, dose, and duration of therapeutic plasma exchange in patients with acute on chronic liver failure is not well described.

  View details for DOI 10.1007/s00431-024-05587-3

  View details for PubMedID 38717620

  View details for PubMedCentralID 4992416

• Intraoperative kidney replacement therapy in acute liver failure PEDIATRIC NEPHROLOGY Henderson, D., Gupta, A., Menon, S., Deep, A. 2024; 39 (10): 2899-2910

  Abstract

  Paediatric acute liver failure (PALF) is often characterised by its rapidity of onset and potential for significant morbidity and even mortality. Patients often develop multiorgan dysfunction/failure, including severe acute kidney injury (AKI). Whilst the management of PALF focuses on complications of hepatic dysfunction, the associated kidney impairment can significantly affect patient outcomes. Severe AKI requiring continuous kidney replacement therapy (CKRT) is a common complication of both PALF and liver transplantation. In both scenarios, the need for CKRT is a poor prognostic indicator. In adults, AKI has been shown to complicate ALF in 25-50% of cases. In PALF, the incidence of AKI is often higher compared to other critically ill paediatric ICU populations, with reports of up to 40% in some observational studies. Furthermore, those presenting with AKI regularly have a more severe grade of PALF at presentation. Observational studies in the paediatric population corroborate this, though data are not as robust-mainly reflecting single-centre cohorts. Perioperative benefits of CKRT include helping to clear water-soluble toxins such as ammonia, balancing electrolytes, preventing fluid overload, and managing raised intracranial pressure. As liver transplantation often takes 6-10 h, it is proposed that these benefits could be extended to the intraoperative period, avoiding any hiatus. Intraoperative CKRT (IoCKRT) has been shown to be practicable, safe and may help sicker recipients tolerate the operation with outcomes analogous with less ill patients not requiring IoCKRT. Here, we provide a comprehensive guide describing the rationale, practicalities, and current evidence base surrounding IoCKRT during transplantation in the paediatric population.

  View details for DOI 10.1007/s00467-023-06272-7

  View details for Web of Science ID 001190489600001

  View details for PubMedID 38526761

  View details for PubMedCentralID PMC11349816

• Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) (vol 9, 732, 2024) KIDNEY INTERNATIONAL REPORTS Menon, S., Krallman, K. A., Arikan, A. A., Fuhrman, D. Y., Gorga, S. M., Mottes, T., Ollberding, N., Ricci, Z., Stanski, N. L., Selewski, D. T., Soranno, D. E., Zappitelli, M., Zang, H., Gist, K. M., WE ROCK Investigators 2024; 9 (3): 732

  Abstract

  [This corrects the article DOI: 10.1016/j.ekir.2023.05.026.].

  View details for DOI 10.1016/j.ekir.2024.01.022

  View details for Web of Science ID 001198912100001

  View details for PubMedID 38481509

  View details for PubMedCentralID PMC10927461

• Continuous Kidney Replacement Therapy and Survival in Children and Young Adults: Findings From the Multi-National WE-ROCK Collaborative. American journal of kidney diseases : the official journal of the National Kidney Foundation Starr, M. C., Gist, K. M., Zang, H., Ollberding, N. J., Balani, S., Cappoli, A., Ciccia, E., Joseph, C., Kakajiwala, A., Kessel, A., Muff-Luett, M., Santiago Lozano, M. J., Pinto, M., Reynaud, S., Solomon, S., Slagle, C., Srivastava, R., Shih, W. V., Webb, T., Menon, S. 2024

  Abstract

  There are limited studies describing the epidemiology and outcomes of children and young adults receiving continuous kidney replacement therapy (CKRT). We aimed to describe associations between patient characteristics, CKRT prescription, and survival.Retrospective multicenter cohort study.& Participants: 980 patients aged birth-25 years old who received CKRT between 2015 and 2021 at 1 of 32 centers in 7 countries participating in the Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Diseases (WE-ROCK).CKRT for acute kidney injury or volume overload.Death before ICU discharge.Descriptive statistics.Median age was 8.8 years (IQR 1.6, 15.0) with a median weight of 26.8 kg (IQR 11.6, 55.0). CKRT was initiated a median of 2 days (IQR 1, 6) after ICU admission and lasted a median of 6 days (IQR 3, 14). The most common CKRT modality was continuous veno-venous hemodiafiltration. Citrate anticoagulation was used in 62%, and the internal jugular vein was the most common catheter placement location (66%). 629 participants (64.1%) survived at least until ICU discharge. The CKRT dose, filter type, and anticoagulation were similar in those who did and did not survive to ICU discharge. There were apparent practice variations by institutional ICU size.Retrospective design; limited representation from centers outside United States.In this study of children and young adults receiving CKRT approximately two-thirds survived at least until ICU discharge. While variations in dialysis mode, dose, catheter size and location, and anticoagulation were observed, survival was not detected to be associated with these parameters.

  View details for DOI 10.1053/j.ajkd.2023.12.017

  View details for PubMedID 38364956

• Time to Continuous Renal Replacement Therapy Initiation and 90-Day Major Adverse Kidney Events in Children and Young Adults. JAMA network open Gist, K. M., Menon, S., Anton-Martin, P., Bigelow, A. M., Cortina, G., Deep, A., De la Mata-Navazo, S., Gelbart, B., Gorga, S., Guzzo, I., Mah, K. E., Ollberding, N. J., Shin, H. S., Thadani, S., Uber, A., Zang, H., Zappitelli, M., Selewski, D. T. 2024; 7 (1): e2349871

  Abstract

  In clinical trials, the early or accelerated continuous renal replacement therapy (CRRT) initiation strategy among adults with acute kidney injury or volume overload has not demonstrated a survival benefit. Whether the timing of initiation of CRRT is associated with outcomes among children and young adults is unknown.To determine whether timing of CRRT initiation, with and without consideration of volume overload (VO; <10% vs ≥10%), is associated with major adverse kidney events at 90 days (MAKE-90).This multinational retrospective cohort study was conducted using data from the Worldwide Exploration of Renal Replacement Outcome Collaborative in Kidney Disease (WE-ROCK) registry from 2015 to 2021. Participants included children and young adults (birth to 25 years) receiving CRRT for acute kidney injury or VO at 32 centers across 7 countries. Statistical analysis was performed from February to July 2023.The primary exposure was time to CRRT initiation from intensive care unit admission.The primary outcome was MAKE-90 (death, dialysis dependence, or persistent kidney dysfunction [>25% decline in estimated glomerular filtration rate from baseline]).Data from 996 patients were entered into the registry. After exclusions (n = 27), 969 patients (440 [45.4%] female; 16 (1.9%) American Indian or Alaska Native, 40 (4.7%) Asian or Pacific Islander, 127 (14.9%) Black, 652 (76.4%) White, 18 (2.1%) more than 1 race; median [IQR] patient age, 8.8 [1.7-15.0] years) with data for the primary outcome (MAKE-90) were included. Median (IQR) time to CRRT initiation was 2 (1-6) days. MAKE-90 occurred in 630 patients (65.0%), of which 368 (58.4%) died. Among the 601 patients who survived, 262 (43.6%) had persistent kidney dysfunction. Of patients with persistent dysfunction, 91 (34.7%) were dependent on dialysis. Time to CRRT initiation was approximately 1 day longer among those with MAKE-90 (median [IQR], 3 [1-8] days vs 2 [1-4] days; P = .002). In the generalized propensity score-weighted regression, there were approximately 3% higher odds of MAKE-90 for each 1-day delay in CRRT initiation (odds ratio, 1.03 [95% CI, 1.02-1.04]).In this cohort study of children and young adults receiving CRRT, longer time to CRRT initiation was associated with greater risk of MAKE-90 outcomes, in particular, mortality. These findings suggest that prospective multicenter studies are needed to further delineate the appropriate time to initiate CRRT and the interaction between CRRT initiation timing and VO to continue to improve survival and reduce morbidity in this population.

  View details for DOI 10.1001/jamanetworkopen.2023.49871

  View details for PubMedID 38165673

  View details for PubMedCentralID PMC10762580

• Optimizing Nutrition in Neonates with Kidney Dysfunction. NeoReviews Nesargi, S., Steflik, H., Kamath, N., Selewski, D., Gist, K. M., Menon, S. 2024; 25 (1): e25-e35

  Abstract

  The nutritional management of neonates with kidney disease is complex. There may be significant differences in nutritional needs based on the duration and cause of kidney dysfunction, including acute kidney injury (AKI) and chronic kidney disease (CKD). Furthermore, the treatment modality, including acute (continuous renal replacement therapy and peritoneal dialysis [PD]) and chronic (intermittent hemodialysis and PD) approaches may differentially affect nutritional losses and dietary needs. In this review, we discuss the pathophysiology of compromised nutrition in neonates with AKI and CKD. We also summarize the existing data and consensus recommendations on the provision of nutrition to neonates with AKI and CKD. We highlight the paucity of data on micronutrient losses and the need for future prospective studies to enhance nutritional supplementation to hopefully improve outcomes in these patients.

  View details for DOI 10.1542/neo.25-1-e25

  View details for PubMedID 38161179

• Moving the neonatal nephrology field forward: results from the Pediatric Academic Society Neonatal Nephrology Focus Group JOURNAL OF PERINATOLOGY Slagle, C., Menon, S., Selewski, D. T., Starr, M. C., Collaborative Co-Authors 2024; 44 (3): 441-443

  View details for DOI 10.1038/s41372-023-01791-5

  View details for Web of Science ID 001107535000001

  View details for PubMedID 37978216

  View details for PubMedCentralID 9756303

• Fluid assessment, fluid balance, and fluid overload in sick children: a report from the Pediatric Acute Disease Quality Initiative (ADQI) conference. Pediatric nephrology (Berlin, Germany) Selewski, D. T., Barhight, M. F., Bjornstad, E. C., Ricci, Z., de Sousa Tavares, M., Akcan-Arikan, A., Goldstein, S. L., Basu, R., Bagshaw, S. M., Pediatric the Acute Disease Quality Initiative (ADQI) Consensus Committee Members, Alobaidi, R., Askenazi, D. J., Barreto, E., Bayrakci, B., Bignall, O. N., Brophy, P., Charlton, J., Chanchlani, R., Conroy, A. L., Deep, A., Devarajan, P., Dolan, K., Fuhrman, D., Gist, K. M., Gorga, S. M., Greenberg, J. H., Hasson, D., Heydari, E., Iyengar, A., Jetton, J., Krawczeski, C., Meigs, L., Menon, S., Morgan, C., Morgan, J., Mottes, T., Neumayr, T., Soranno, D., Stanski, N., Starr, M., Sutherland, S. M., Symons, J., Vega, M., Zappitelli, M., Ronco, C., Mehta, R. L., Kellum, J., Ostermann, M. 2023

  Abstract

  BACKGROUND: The impact of disorders of fluid balance, including the pathologic state of fluid overload in sick children has become increasingly apparent. With this understanding, there has been a shift from application of absolute thresholds of fluid accumulation to an appreciation of the intricacies of fluid balance, including the impact of timing, trajectory, and disease pathophysiology.METHODS: The 26th Acute Disease Quality Initiative was the first to be exclusively dedicated to pediatric and neonatal acute kidney injury (pADQI). As part of the consensus panel, a multidisciplinary working group dedicated to fluid balance, fluid accumulation, and fluid overload was created. Through a search, review, and appraisal of the literature, summative consensus statements, along with identification of knowledge gaps and recommendations for clinical practice and research were developed.CONCLUSIONS: The 26th pADQI conference proposed harmonized terminology for fluid balance and for describing a pathologic state of fluid overload for clinical practice and research. Recommendations include that the terms daily fluid balance, cumulative fluid balance, and percent cumulative fluid balance be utilized to describe the fluid status of sick children. The term fluid overload is to be preserved for describing a pathologic state of positive fluid balance associated with adverse events. Several recommendations for research were proposed including focused validation of the definition of fluid balance, fluid overload, and proposed methodologic approaches and endpoints for clinical trials.

  View details for DOI 10.1007/s00467-023-06156-w

  View details for PubMedID 37934274

• Pediatric AKI in the real world: changing outcomes through education and advocacy-a report from the 26th Acute Disease Quality Initiative (ADQI) consensus conference. Pediatric nephrology (Berlin, Germany) Mottes, T., Menon, S., Conroy, A., Jetton, J., Dolan, K., Arikan, A. A., Basu, R. K., Goldstein, S. L., Symons, J. M., Alobaidi, R., Askenazi, D. J., Bagshaw, S. M., Barhight, M., Barreto, E., Bayrakci, B., Ray, O. N., Bjornstad, E., Brophy, P., Charlton, J., Chanchlani, R., Conroy, A. L., Deep, A., Devarajan, P., Fuhrman, D., Gist, K. M., Gorga, S. M., Greenberg, J. H., Hasson, D., Heydari, E., Iyengar, A., Krawczeski, C., Meigs, L., Morgan, C., Morgan, J., Neumayr, T., Ricci, Z., Selewski, D. T., Soranno, D., Stanski, N., Starr, M., Sutherland, S. M., Symons, J., Tavares, M., Vega, M., Zappitelli, M., Ronco, C., Mehta, R. L., Kellum, J., Ostermann, M., ADQI 26 workgroup 2023

  Abstract

  BACKGROUND: Acute kidney injury (AKI) is independently associated with increased morbidity and mortality across the life course, yet care for AKI remains mostly supportive. Raising awareness of this life-threatening clinical syndrome through education and advocacy efforts is the key to improving patient outcomes. Here, we describe the unique roles education and advocacy play in the care of children with AKI, discuss the importance of customizing educational outreach efforts to individual groups and contexts, and highlight the opportunities created through innovations and partnerships to optimize lifelong health outcomes.METHODS: 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 on AKI research, education, practice, and advocacy in children.RESULTS: The consensus statements developed in response to three critical questions about the role of education and advocacy in pediatric AKI care are presented here along with a summary of available evidence and recommendations for both clinical care and research.CONCLUSIONS: These consensus statements emphasize that high-quality care for patients with AKI begins in the community with education and awareness campaigns to identify those at risk for AKI. Education is the key across all healthcare and non-healthcare settings to enhance early diagnosis and develop mitigation strategies, thereby improving outcomes for children with AKI. Strong advocacy efforts are essential for implementing these programs and building critical collaborations across all stakeholders and settings.

  View details for DOI 10.1007/s00467-023-06180-w

  View details for PubMedID 37934273

• Programs and processes for advancing pediatric acute kidney support therapy in hospitalized and critically ill children: a report from the 26th Acute Disease Quality Initiative (ADQI) consensus conference. Pediatric nephrology (Berlin, Germany) Neumayr, T. M., Bayrakci, B., Chanchlani, R., Deep, A., Morgan, J., Arikan, A. A., Basu, R. K., Goldstein, S. L., Askenazi, D. J., ADQI 26 workgroup, Alobaidi, R., Bagshaw, S. M., Barhight, M., Barreto, E., Ray, O. N., Bjornstad, E., Brophy, P., Charlton, J., Conroy, A. L., Devarajan, P., Dolan, K., Fuhrman, D., Gist, K. M., Gorga, S. M., Greenberg, J. H., Hasson, D., Heydari, E., Iyengar, A., Jetton, J., Krawczeski, C., Meigs, L., Menon, S., Morgan, C., Mottes, T., Ricci, Z., Selewski, D. T., Soranno, D., Stanski, N., Starr, M., Sutherland, S. M., Symons, J., Tavares, M., Vega, M., Zappitelli, M., Ronco, C., Mehta, R. L., Kellum, J., Ostermann, M. 2023

  Abstract

  Pediatric acute kidney support therapy (paKST) programs aim to reliably provide safe, effective, and timely extracorporeal supportive care for acutely and critically ill pediatric patients with acute kidney injury (AKI), fluid and electrolyte derangements, and/or toxin accumulation with a goal of improving both hospital-based and lifelong outcomes. Little is known about optimal ways to configure paKST teams and programs, pediatric-specific aspects of delivering high-quality paKST, strategies for transitioning from acute continuous modes of paKST to facilitate rehabilitation, or providing effective short- and long-term follow-up. As part of the 26th Acute Disease Quality Initiative Conference, the first to focus on a pediatric population, we summarize here the current state of knowledge in paKST programs and technology, identify key knowledge gaps in the field, and propose a framework for current best practices and future research in paKST.

  View details for DOI 10.1007/s00467-023-06186-4

  View details for PubMedID 37930418

• 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

• An update on the role of fluid overload in the prediction of outcome in acute kidney injury PEDIATRIC NEPHROLOGY Gorga, S. M., Selewski, D. T., Goldstein, S. L., Menon, S. 2024; 39 (7): 2033-2048

  Abstract

  Over the past two decades, our understanding of the impact of acute kidney injury, disorders of fluid balance, and their interplay have increased significantly. In recent years, the epidemiology and impact of fluid balance, including the pathologic state of fluid overload on outcomes has been studied extensively across multiple pediatric and neonatal populations. A detailed understating of fluid balance has become increasingly important as it is recognized as a target for intervention to continue to work to improve outcomes in these populations. In this review, we provide an update on the epidemiology and outcomes associated with fluid balance disorders and the development of fluid overload in children with acute kidney injury (AKI). This will include a detailed review of consensus definitions of fluid balance, fluid overload, and the methodologies to define them, impact of fluid balance on the diagnosis of AKI and the concept of fluid corrected serum creatinine. This review will also provide detailed descriptions of future directions and the changing paradigms around fluid balance and AKI in critical care nephrology, including the incorporation of the sequential utilization of risk stratification, novel biomarkers, and functional kidney tests (furosemide stress test) into research and ultimately clinical care. Finally, the review will conclude with novel methods currently under study to assess fluid balance and distribution (point of care ultrasound and bioimpedance).

  View details for DOI 10.1007/s00467-023-06161-z

  View details for Web of Science ID 001088047900001

  View details for PubMedID 37861865

  View details for PubMedCentralID 5267552

• Therapeutic plasma exchange for mechanical red cell hemolysis: A case series JOURNAL OF CLINICAL APHERESIS Douglas, C. E., House, T. R., Yalon, L., Menon, S. 2024; 39 (1): e22093

  Abstract

  We present three cases of severely elevated plasma free hemoglobin (PFH) in pediatric patients on mechanical circulatory support devices at a tertiary pediatric care center. Due to severe levels of PFH in the setting of critical illness with the inability to pursue immediate mechanical device exchange, membrane filtration therapeutic plasma exchange (TPE) was performed, which resulted in a lowering of PFH levels. However, long-term outcomes were heterogeneous across the cases. This case series reviews patient presentation, organ function before and after TPE, and the overall role of TPE as an effective treatment option to decrease severely elevated PFH levels. In doing so, we hope to add to what is known about the use of TPE for mechanical red cell hemolysis and provide guidance on its use in critically ill patients.

  View details for DOI 10.1002/jca.22093

  View details for Web of Science ID 001087968800001

  View details for PubMedID 37850483

  View details for PubMedCentralID PMC10922221

• 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

• A proposed framework for advancing acute kidney injury risk stratification and diagnosis in children: a report from the 26th Acute Disease Quality Initiative (ADQI) conference. Pediatric nephrology (Berlin, Germany) Fuhrman, D. Y., Stanski, N. L., Krawczeski, C. D., Greenberg, J. H., Arikan, A. A., Basu, R. K., Goldstein, S. L., Gist, K. M., ADQI 26 workgroup, Alobaidi, R., Askenazi, D. J., Bagshaw, S. M., Barhight, M., Barreto, E., Bayrakci, B., Ray Bignall, O. N., Bjornstad, E., Brophy, P., Charlton, J., Chanchlani, R., Conroy, A. L., Deep, A., Devarajan, P., Dolan, K., Fuhrman, D., Gist, K. M., Gorga, S. M., Greenberg, J. H., Hasson, D., Heydari, E., Iyengar, A., Jetton, J., Krawczeski, C., Meigs, L., Menon, S., Morgan, C., Morgan, J., Mottes, T., Neumayr, T., Ricci, Z., Selewski, D. T., Soranno, D., Stanski, N., Starr, M., Sutherland, S. M., Symons, J., Tavares, M., Vega, M., Zappitelli, M., Ronco, C., Mehta, R. L., Kellum, J., Ostermann, M. 2023

  Abstract

  Acute kidney injury (AKI) in children is associated with increased morbidity, reduced health-related quality of life, greater resource utilization, and higher mortality. Improvements in the timeliness and precision of AKI diagnosis in children are needed. In this report, we highlight existing, novel, and on-the-horizon diagnostic and risk-stratification tools for pediatric AKI, and outline opportunities for integration into clinical practice. We also summarize pediatric-specific high-risk diagnoses and exposures for AKI, as well as the potential role of real-time risk stratification and clinical decision support to improve outcomes. Lastly, the key characteristics of important pediatric AKI phenotypes will be outlined. Throughout, we identify key knowledge gaps, which represent prioritized areas of focus for future research that will facilitate a comprehensive, timely and personalized approach to pediatric AKI diagnosis and management.

  View details for DOI 10.1007/s00467-023-06133-3

  View details for PubMedID 37670082

• Caffeine and kidney function at two years in former extremely low gestational age neonates PEDIATRIC RESEARCH Harer, M. W., Griffin, R., Askenazi, D. J., Fuloria, M., Guillet, R., Hanna, M., Schuh, M. P., Slagle, C., Woroniecki, R., DeFreitas, M., Gist, K. M., Menon, S., Nesargi, S., Raina, R., Sanderson, K., Segar, J. L., Selewski, D. T., South, A. M., Steflik, H. J., Starr, M. C., Swanson, J. R., Zappitelli, M., Charlton, J. R., Neonatal Kidney Collaborative 2024; 95 (1): 257-266

  Abstract

  Extremely low gestational age neonates (ELGANs) are at risk for chronic kidney disease. The long-term kidney effects of neonatal caffeine are unknown. We hypothesize that prolonged caffeine exposure will improve kidney function at 22-26 months.Secondary analysis of the Preterm Erythropoietin Neuroprotection Trial of neonates <28 weeks' gestation. Participants included if any kidney outcomes were collected at 22-26 months corrected age. Exposure was post-menstrual age of caffeine discontinuation.'reduced eGFR' <90 ml/min/1.73 m2, 'albuminuria' (>30 mg albumin/g creatinine), or 'elevated blood pressure' (BP) >95th %tile. A general estimating equation logistic regression model stratified by bronchopulmonary dysplasia (BPD) status was used.598 participants had at least one kidney metric at follow up. Within the whole cohort, postmenstrual age of caffeine discontinuation was not associated with any abnormal measures of kidney function at 2 years. In the stratified analysis, for each additional week of caffeine, the no BPD group had a 21% decreased adjusted odds of eGFR <90 ml/min/1.73m2 (aOR 0.78; CI 0.62-0.99) and the BPD group had a 15% increased adjusted odds of elevated BP (aOR 1.15; CI: 1.05-1.25).Longer caffeine exposure during the neonatal period is associated with differential kidney outcomes at 22-26 months dependent on BPD status.In participants born <28 weeks' gestation, discontinuation of caffeine at a later post menstrual age was not associated with abnormal kidney outcomes at 22-26 months corrected age. When assessed at 2 years of age, later discontinuation of caffeine in children born <28 weeks' gestation was associated with a greater risk of reduced eGFR in those without a history of BPD and an increased odds of hypertension in those with a history of BPD. More work is necessary to understand the long-term impact of caffeine on the developing kidney.

  View details for DOI 10.1038/s41390-023-02792-y

  View details for Web of Science ID 001060845400002

  View details for PubMedID 37660176

  View details for PubMedCentralID PMC11293578

• Subphenotypes of Pediatric Acute Kidney Injury NEPHRON Menon, S., Gist, K. M. 2023: 743-746

  Abstract

  Acute kidney injury (AKI) is seen frequently in hospitalized patients and is associated with increased risk of mortality and adverse short- and long-term renal and systemic complications. Emerging data suggest that AKI is a heterogenous syndrome with a variety of underlying causes, predisposing illnesses, and range of clinical trajectories and outcomes. This mini-review aims to discuss emerging AKI subphenotype classifications as our understanding of the heterogeneity and underlying pathophysiology has improved.

  View details for DOI 10.1159/000531914

  View details for Web of Science ID 001093639000001

  View details for PubMedID 37598663

• Acute Kidney Injury Defined by Fluid-Corrected Creatinine in Premature Neonates A Secondary Analysis of the PENUT Randomized Clinical Trial JAMA NETWORK OPEN Starr, M. C., Griffin, R. L., Harer, M. W., Soranno, D. E., Gist, K. M., Segar, J. L., Menon, S., Gordon, L., Askenazi, D. J., Selewski, D. T. 2023; 6 (8): e2328182

  Abstract

  Acute kidney injury (AKI) and disordered fluid balance are common in premature neonates; a positive fluid balance dilutes serum creatinine, and a negative fluid balance concentrates serum creatinine, both of which complicate AKI diagnosis. Correcting serum creatinine for fluid balance may improve diagnosis and increase diagnostic accuracy for AKI.To determine whether correcting serum creatinine for fluid balance would identify additional neonates with AKI and alter the association of AKI with short-term and long-term outcomes.This study was a post hoc cohort analysis of the Preterm Erythropoietin Neuroprotection Trial (PENUT), a phase 3, randomized clinical trial of erythropoietin, conducted at 19 academic centers and 30 neonatal intensive care units in the US from December 2013 to September 2016. Participants included extremely premature neonates born at less than 28 weeks of gestation. Data analysis was conducted in December 2022.Diagnosis of fluid-corrected AKI during the first 14 postnatal days, calculated using fluid-corrected serum creatinine (defined as serum creatinine multiplied by fluid balance [calculated as percentage change from birth weight] divided by total body water [estimated 80% of birth weight]).The primary outcome was invasive mechanical ventilation on postnatal day 14. Secondary outcomes included death, hospital length of stay, and severe bronchopulmonary dysplasia (BPD). Categorical variables were analyzed by proportional differences with the χ2 test or Fisher exact test. The t test and Wilcoxon rank sums test were used to compare continuous and ordinal variables, respectively. Odds ratios (ORs) and 95% CIs for the association of exposure with outcomes of interest were estimated using unconditional logistic regression models.A total of 923 premature neonates (479 boys [51.9%]; median [IQR] birth weight, 801 [668-940] g) were included, of whom 215 (23.3%) received a diagnosis of AKI using uncorrected serum creatinine. After fluid balance correction, 13 neonates with AKI were reclassified as not having fluid-corrected AKI, and 111 neonates previously without AKI were reclassified as having fluid-corrected AKI (ie, unveiled AKI). Therefore, fluid-corrected AKI was diagnosed in 313 neonates (33.9%). Neonates with unveiled AKI were similar in clinical characteristics to those with AKI whose diagnoses were made with uncorrected serum creatinine. Compared with those without AKI, neonates with unveiled AKI were more likely to require ventilation (81 neonates [75.0%] vs 254 neonates [44.3%] and have longer hospital stays (median [IQR], 102 [84-124] days vs 90 [71-110] days). In multivariable analysis, a diagnosis of fluid-corrected AKI was associated with increased odds of adverse clinical outcomes, including ventilation (adjusted OR, 2.23; 95% CI, 1.56-3.18) and severe BPD (adjusted OR, 2.05; 95% CI, 1.15-3.64).In this post hoc cohort study of premature neonates, fluid correction increased the number of premature neonates with a diagnosis of AKI and was associated with increased odds of adverse clinical outcomes, including ventilation and BPD. Failing to correct serum creatinine for fluid balance underestimates the prevalence and impact of AKI in premature neonates. Future studies should consider correcting AKI for fluid balance.ClinicalTrials.gov Identifier: NCT01378273.

  View details for DOI 10.1001/jamanetworkopen.2023.28182

  View details for Web of Science ID 001061920200003

  View details for PubMedID 37561461

  View details for PubMedCentralID PMC10415963

• Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK). Kidney international reports Menon, S., Krallman, K. A., Arikan, A. A., Fuhrman, D. Y., Gorga, S. M., Mottes, T., Ollberding, N., Ricci, Z., Stanski, N. L., Selewski, D. T., Soranno, D. E., Zappitelli, M., Zang, H., Gist, K. M., WE-ROCK Investigators, Ahern, E., Akcan Arikan, A., Alhamoud, I., Alobaidi, R., Anton-Martin, P., Balani, S. S., Barhight, M., Basalely, A., Bigelow, A. M., Bottari, G., Cappoli, A., Ciccia, E. A., Collins, M., Colosimo, D., Cortina, G., Damian, M. A., De la Mata Navazo, S., DeAbreu, G., Deep, A., Ding, K. L., Dolan, K. J., Fernandez Lafever, S. N., Fuhrman, D. Y., Gelbart, B., Gist, K. M., Gorga, S. M., Guzzi, F., Guzzo, I., Haga, T., Harvey, E., Hasson, D. C., Hill-Horowitz, T., Inthavong, H., Joseph, C., Kaddourah, A., Kakajiwala, A., Kessel, A. D., Korn, S., Krallman, K. A., Kwiatkowski, D. M., Lee, J., Lequier, L., Kia, T. M., Mah, K. E., Marinari, E., Martin, S. D., Menon, S., Mohamed, T. H., Morgan, C., Mottes, T. A., Muff-Luett, M. A., Namachivayam, S., Neumayr, T. M., Md, J. N., O'Rourke, A., Ollberding, N. J., Pinto, M. G., Qutob, D., Raggi, V., Reynaud, S., Ricci, Z., Rumlow, Z. A., Santiago Lozano, M. J., See, E., Selewski, D. T., Serpe, C., Serratore, A., Shah, A., Shih, W. V., Shin, H. S., Slagle, C. L., Solomon, S., Soranno, D. E., Srivastava, R., Stanski, N. L., Starr, M. C., Stenson, E. K., Strong, A. E., Taylor, S. A., Thadani, S. V., Uber, A. M., Van Wyk, B., Webb, T. N., Zang, H., Zangla, E. E., Zappitelli, M. 2023; 8 (8): 1542-1552

  Abstract

  Introduction: Continuous renal replacement therapy (CRRT) is used for the symptomatic management of acute kidney injury (AKI) and fluid overload (FO). Contemporary reports on pediatric CRRT are small and single center in design. Large international studies evaluating CRRT practice and outcomes are lacking. Herein, we describe the design of a multinational collaborative.Methods: The Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) is an international collaborative of pediatric specialists whose mission is to improve short- and long-term outcomes of children treated with CRRT. The aims of this multicenter retrospective study are to describe the epidemiology, liberation patterns, association of fluid balance and timing of CRRT initiation, and CRRT prescription with outcomes.Results: We included children (n= 996, 0-25 years) admitted to an intensive care unit (ICU) and treated with CRRT for AKI or FO at 32 centers (in 7 countries) from 2018 to 2021. Demographics and clinical characteristics before CRRT initiation, during the first 7 days of both CRRT, and liberation were collected. Outcomes include the following: (i) major adverse kidney events at 90 days (mortality, dialysis dependence, and persistent kidney dysfunction), and (ii) functional outcomes (functional stats scale).Conclusion: The retrospective WE-ROCK study represents the largest international registry of children receiving CRRT for AKI or FO. It will serve as a broad and invaluable resource for the field of pediatric critical care nephrology that will improve our understanding of practice heterogeneity and the association of CRRT with clinical and patient-centered outcomes. This will generate preliminary data for future interventional trials in this area.

  View details for DOI 10.1016/j.ekir.2023.05.026

  View details for PubMedID 37547524

• Use of the Seraph® 100 Microbind® Affinity Blood Filter in an adolescent patient with disseminated adenoviral disease PEDIATRIC NEPHROLOGY Li, D. S., Burke, T. M., Smith, J. M., Reed, R. C., Okamura, D. M., Menon, S. 2024; 39 (1): 331-335

  Abstract

  The Seraph® 100 Microbind® Affinity Blood Filter (Seraph® 100) is an adjunctive pathogen adsorption device with emergency use authorization for use with extracorporeal therapies to treat COVID-19 infection.Here, we describe the use of Seraph® 100 in a 17-year-old chronically immunosuppressed patient status post deceased donor kidney transplant who presented initially for hematuria, dysuria, and fevers, and was found to have disseminated adenovirus (ADV) infection complicated by nephritis, viral pneumonia, elevated transaminases, and bone marrow suppression. Despite halting immunosuppression for 2 weeks, she remained febrile to 40.2 °C, with serum ADV counts > 10 million copies/mL (> log 7). Due to concerns about nephrotoxicity from cidofovir treatment, she underwent 2 intermittent treatments with Seraph® 100 to reduce viral load. Fever curve, blood counts, and transaminases stabilized in the days following treatment, and the patient was able to resume her prior immunosuppression regimen without a rebound in viral counts.This adolescent kidney transplant patient with disseminated ADV infection tolerated in-line treatment with Seraph® 100 without major clinical adverse events related to the adsorber, and had resolution of her ADV infection and good clinical recovery.

  View details for DOI 10.1007/s00467-023-06097-4

  View details for Web of Science ID 001039843900001

  View details for PubMedID 37505308

  View details for PubMedCentralID 8169409

• Approaches to evaluation of fluid balance and management of fluid overload in neonates among neonatologists: a Neonatal Kidney Collaborative survey JOURNAL OF PERINATOLOGY Gordon, L., Grossmann, K., Guillet, R., Steflik, H., Harer, M. W., Askenazi, D. J., Menon, S., Selewski, D. T., Starr, M. C. 2023; 43 (10): 1314-1315

  View details for DOI 10.1038/s41372-023-01738-w

  View details for Web of Science ID 001032342600001

  View details for PubMedID 37481631

  View details for PubMedCentralID 9756303

• Acute Kidney Injury PEDIATRICS IN REVIEW Menon, S., Symons, J. M., Selewski, D. T. 2023; 44 (5): 265-279

  Abstract

  Acute kidney injury (AKI) has been shown to occur commonly in hospitalized children. AKI is associated with multiple complications, including elevated blood urea nitrogen level, electrolyte dyscrasias, acidosis, and fluid balance disorders. During the past 10 years, multiple multicenter studies have shown that AKI occurs commonly and is associated with adverse outcomes across a variety of populations in pediatrics. This state-of-the-art review provides a detailed overview and update on AKI, including definition, epidemiology, outcomes, differential diagnosis, diagnostics, and management of complications.

  View details for DOI 10.1542/pir.2021-005438

  View details for Web of Science ID 001049109700004

  View details for PubMedID 37122039

• Adherence to Hypertension Guidelines in Children-What Is All the Hype? JAMA NETWORK OPEN Gist, K. M., Menon, S. 2023; 6 (4): e237002

  View details for DOI 10.1001/jamanetworkopen.2023.7002

  View details for Web of Science ID 001046682600004

  View details for PubMedID 37058310

• Incidence and risk factors of acute kidney injury among childhood nephrotic syndrome: a prospective cohort study EUROPEAN JOURNAL OF PEDIATRICS Ghosh, S., Akhtar, S., Pradhan, S., Sarkar, S., Dasgupta, D., Parween, R., Menon, S., Sinha, R. 2023; 182 (5): 2443-2451

  Abstract

  Acute kidney injury (AKI) is a known independent risk factor for morbidity/mortality but there is scarcity of robust data on it among childhood nephrotic syndrome (NS). We assessed the incidence of AKI among hospitalized children with NS as well as looked for any significant risk factors. Prospective observational study conducted across two tertiary pediatric hospitals in Eastern India from September 2020 to August 2021. Children aged 1-18 years admitted with NS and without any nephritic features or pre-existing chronic kidney disease (CKD) were included. In 200 admissions (n = 176; 63% female, median age 4 years [IQR: 3-7]), AKI occurred in 36 (18%; 95% CI 13 to 36%). Two children required kidney replacement therapy and one death was recorded. In 27/36 (75%), AKI resolved within 48 h, 4 had persistent AKI, 3 acute kidney disease, and two progressed to CKD. On multivariate regression analysis: fractional excretion of sodium ≤ 0.2% (OR 12.77; 95% CI 3.5-46.4), male gender (OR 6.38; 95% CI 2.76-14.74), underlying infection (OR 5.44; 95% CI 2.4-11.86), nephrotoxic drugs (OR 4.83; 95% CI 2.21-10.54), and albumin ≤ 1.4 g/dl (OR 4.35; 95% CI 1.55-12.8) were associated with AKI. A predictive equation using these five variables on admission had high AUC (0.86) in correctly identifying 17 children who subsequently developed AKI.   Conclusion: In a low resource setting, AKI is common among hospitalized children with NS. Larger multi-center prospective studies are needed to refine prediction equations and test its utility in preventing AKI development. What is Known: • Acute Kidney Injury is a known independent risk factor for increased morbidity and mortality. • There are few studies to assess the incidence of Acute kidney injury in hospitalised cases of childhood nephrotic syndrome.. What is New: • This is the largest prospective cohort of children suffering from nephrotic syndrome, in India, proposing a novel algorithm for predicting the risk of AKI among hospitalised cases of childhood nephrotic syndrome.

  View details for DOI 10.1007/s00431-023-04903-7

  View details for Web of Science ID 000952515700001

  View details for PubMedID 36920554

  View details for PubMedCentralID 4835686

• Sepsis and AKI: A Two-Way Street KIDNEY360 Basalely, A., Menon, S. 2023; 4 (3): 289-290

  View details for DOI 10.34067/KID.0000000000000106

  View details for Web of Science ID 000970062500001

  View details for PubMedID 36996291

  View details for PubMedCentralID PMC10103326

• Association of Fluid Balance With Short- and Long-term Respiratory Outcomes in Extremely Premature Neonates: A Secondary Analysis of a Randomized Clinical Trial JAMA NETWORK OPEN Starr, M. C., Griffin, R., Gist, K. M., Segar, J. L., Raina, R., Guillet, R., Nesargi, S., Menon, S., Anderson, N., Askenazi, D. J., Selewski, D. T., Neonatal Kidney Collaborative Res 2022; 5 (12): e2248826

  Abstract

  Extremely low gestational age neonates are at risk of disorders of fluid balance (FB), defined as change in fluid weight over a specific period. Few data exist on the association between FB and respiratory outcomes in this population.To describe FB patterns and evaluate the association of FB with respiratory outcomes in a cohort of extremely low gestational age neonates.This study is a secondary analysis of the Preterm Erythropoietin Neuroprotection Trial (PENUT), a phase 3 placebo-controlled randomized clinical trial of erythropoietin in extremely premature neonates conducted in 30 neonatal intensive care units in the US from December 1, 2013, to September 31, 2016. This analysis included 874 extremely premature neonates born at 24 to 27 weeks' gestation who were enrolled in the PENUT study. Secondary analysis was performed in November 2021.Primary exposure was peak FB during the first 14 postnatal days. The FB was calculated as percent change in weight from birth weight (BW) as a surrogate for FB.The primary outcome was mechanical ventilation on postnatal day 14. The secondary outcome was a composite of severe bronchopulmonary dysplasia (BPD) or death.A total of 874 neonates (449 [51.4%] male; mean [SD] BW, 801 [188] g; 187 [21.4%] Hispanic, 676 [77.3%] non-Hispanic, and 11 [1.3%] of unknown ethnicity; 226 [25.9%] Black, 569 [65.1%] White, 51 [5.8%] of other race, and 28 [3.2%] of unknown race) were included in this analysis. Of these 874 neonates, 458 (52.4%) received mechanical ventilation on postnatal day 14, and 291 (33.3%) had severe BPD or had died. Median peak positive FB was 11% (IQR, 4%-20%), occurring on postnatal day 13 (IQR, 9-14). A total of 93 (10.6%) never decreased below their BW. Neonates requiring mechanical ventilation at postnatal day 14 had a higher peak FB compared with those who did not require mechanical ventilation (15% above BW vs 8% above BW, P < .001). On postnatal day 3, neonates requiring mechanical ventilation were more likely to have a higher FB (5% below BW vs 8% below BW, P < .001). The median time to return to BW was shorter in neonates who received mechanical ventilation (7 vs 8 days, P < .001) and those with severe BPD (7 vs 8 days, P < .001). After adjusting for confounding variables, for every 10% increase in peak FB during the first 14 postnatal days, there was 103% increased odds of receiving mechanical ventilation at postnatal day 14 (adjusted odds ratio, 2.03; 95% CI, 1.64-2.51).In this secondary analysis of a randomized clinical trial, peak FB was associated with mechanical ventilation on postnatal day 14 and severe BPD or death. Fluid balance in the first 3 postnatal days and time to return to BW may be potential targets to help guide management and improve respiratory outcomes.ClinicalTrials.gov Identifier: NCT01378273.

  View details for DOI 10.1001/jamanetworkopen.2022.48826

  View details for Web of Science ID 000919609800006

  View details for PubMedID 36580332

  View details for PubMedCentralID PMC9856967

• Subphenotypes of acute kidney injury in children CURRENT OPINION IN CRITICAL CARE Gist, K. M., Fuhrman, D., Stanski, N., Menon, S., Soranno, D. E. 2022; 28 (6): 590-598

  Abstract

  The purpose of this review is to describe acute kidney injury (AKI) phenotypes in children.AKI is a heterogenous disease that imposes significant morbidity and mortality on critically ill and noncritically ill patients across the age spectrum. As our understanding of AKI and its association with outcomes has improved, it is becoming increasingly apparent that there are distinct AKI subphenotypes that vary by cause or associated conditions. We have also learned that severity, duration, and repeated episodes of AKI impact outcomes, and that integration of novel urinary biomarkers of tubular injury can also reveal unique subphenotypes of AKI that may not be otherwise readily apparent.Studies that further delineate these unique AKI subphenotypes are needed to better understand the impact of AKI in children. Further delineation of these phenotypes has both prognostic and therapeutic implications.

  View details for DOI 10.1097/MCC.0000000000000986

  View details for Web of Science ID 000874085100004

  View details for PubMedID 36044290

  View details for PubMedCentralID PMC9612688

• Update on Pediatric Acute Kidney Injury PEDIATRIC CLINICS OF NORTH AMERICA Khandelwal, P., McLean, N., Menon, S. 2022; 69 (6): 1219-1238

  Abstract

  Acute kidney injury (AKI) is common in children and is associated with significant morbidity and mortality. In the last decade our understanding of AKI has improved significantly, and it is now considered a systemic disorder that affects other organs including heart, lung, and brain. In spite of its limitations, serum creatinine remains the mainstay in the diagnosis of AKI. However, newer approaches such as urinary biomarkers, furosemide stress test, and clinical decision support are being increasingly used and have the potential to improve the accuracy and timeliness of AKI diagnosis.

  View details for DOI 10.1016/j.pcl.2022.08.003

  View details for Web of Science ID 000883475400013

  View details for PubMedID 36880931

• Kidney support for babies: building a comprehensive and integrated neonatal kidney support therapy program PEDIATRIC NEPHROLOGY Mohamed, T. H., Morgan, J., Mottes, T. A., Askenazi, D., Jetton, J. G., Menon, S. 2023; 38 (7): 2043-2055

  Abstract

  Kidney support therapy (KST), previously referred to as Renal Replacement Therapy, is utilized to treat children and adults with severe acute kidney injury (AKI), fluid overload, inborn errors of metabolism, and kidney failure. Several forms of KST are available including peritoneal dialysis (PD), intermittent hemodialysis (iHD), and continuous kidney support therapy (CKST). Traditionally, extracorporeal KST (CKST and iHD) in neonates has had unique challenges related to small patient size, lack of neonatal-specific devices, and risk of hemodynamic instability due to large extracorporeal circuit volume relative to patient total blood volume. Thus, PD has been the most commonly used modality in infants, followed by CKST and iHD. In recent years, CKST machines designed for small children and novel filters with smaller extracorporeal circuit volumes have emerged and are being used in many centers to provide neonatal KST for toxin removal and to achieve fluid and electrolyte homeostasis, increasing the options available for this unique and vulnerable group. These new treatment options create a dramatic paradigm shift with recalibration of the benefit: risk equation. Renewed focus on the infrastructure required to deliver neonatal KST safely and effectively is essential, especially in programs/units that do not traditionally provide KST to neonates. Building and implementing a neonatal KST program requires an expert multidisciplinary team with strong institutional support. In this review, we first describe the available neonatal KST modalities including newer neonatal and infant-specific platforms. Then, we describe the steps needed to develop and sustain a neonatal KST team, including recommendations for provider and nursing staff training. Finally, we describe how quality improvement initiatives can be integrated into programs.

  View details for DOI 10.1007/s00467-022-05768-y

  View details for Web of Science ID 000867600200004

  View details for PubMedID 36227440

  View details for PubMedCentralID 2755787

• Association of Renin Angiotensin Aldosterone System Inhibitors and Outcomes of Hospitalized Patients With COVID-19 CRITICAL CARE MEDICINE Gupta, N., Settle, L., Brown, B. R., Armaignac, D. L., Baram, M., Perkins, N. E., Kaufman, M., Melamed, R. R., Christie, A. B., Danesh, V. C., Denson, J. L., Cheruku, S. R., Boman, K., Bansal, V., Kumar, V. K., Walkey, A. J., Domecq, J. P., Kashyap, R., Aston, C. E., Soc Critical Care Med Discovery Vi 2022; 50 (10): E744-E758

  Abstract

  To determine the association of prior use of renin-angiotensin-aldosterone system inhibitors (RAASIs) with mortality and outcomes in hospitalized patients with COVID-19.Retrospective observational study.Multicenter, international COVID-19 registry.Adult hospitalized COVID-19 patients on antihypertensive agents (AHAs) prior to admission, admitted from March 31, 2020, to March 10, 2021.None.Data were compared between three groups: patients on RAASIs only, other AHAs only, and those on both medications. Multivariable logistic and linear regressions were performed after controlling for prehospitalization characteristics to estimate the effect of RAASIs on mortality and other outcomes during hospitalization. Of 26,652 patients, 7,975 patients were on AHAs prior to hospitalization. Of these, 1,542 patients (19.3%) were on RAASIs only, 3,765 patients (47.2%) were on other AHAs only, and 2,668 (33.5%) patients were on both medications. Compared with those taking other AHAs only, patients on RAASIs only were younger (mean age 63.3 vs 66.9 yr; p < 0.0001), more often male (58.2% vs 52.4%; p = 0.0001) and more often White (55.1% vs 47.2%; p < 0.0001). After adjusting for age, gender, race, location, and comorbidities, patients on combination of RAASIs and other AHAs had higher in-hospital mortality than those on RAASIs only (odds ratio [OR] = 1.28; 95% CI [1.19-1.38]; p < 0.0001) and higher mortality than those on other AHAs only (OR = 1.09; 95% CI [1.03-1.15]; p = 0.0017). Patients on RAASIs only had lower mortality than those on other AHAs only (OR = 0.87; 95% CI [0.81-0.94]; p = 0.0003). Patients on ACEIs only had higher mortality compared with those on ARBs only (OR = 1.37; 95% CI [1.20-1.56]; p < 0.0001).Among patients hospitalized for COVID-19 who were taking AHAs, prior use of a combination of RAASIs and other AHAs was associated with higher in-hospital mortality than the use of RAASIs alone. When compared with ARBs, ACEIs were associated with significantly higher mortality in hospitalized COVID-19 patients.

  View details for DOI 10.1097/CCM.0000000000005627

  View details for Web of Science ID 000863526100001

  View details for PubMedID 35894609

  View details for PubMedCentralID PMC9469914

• Risk factors for severe acute kidney injury after pediatric hematopoietic cell transplantation PEDIATRIC NEPHROLOGY Bauer, A., Carlin, K., Schwartz, S. M., Srikanthan, M., Thakar, M., Burroughs, L. M., Smith, J., Hingorani, S., Menon, S. 2023; 38 (4): 1365-1372

  Abstract

  Acute kidney injury (AKI) is common after hematopoietic cell transplantation (HCT) and is associated with poorer outcomes. Risk factors for AKI after pediatric HCT are not fully understood. The study objective was to assess unique risk factors for AKI in the HCT population and evaluate post-HCT AKI patterns.We conducted a retrospective cohort study of patients < 21 years of age who underwent HCT at Seattle Children's Hospital/Fred Hutchinson Cancer Center from September 2008 to July 2017 (n = 484). We defined AKI using KDIGO criteria. We collected demographics, baseline HCT characteristics, post-HCT complications, and mortality. Multinomial logistic regression was used to estimate association between AKI and potential risk factors. We used adjusted Cox proportional hazard ratios to evaluate differences in mortality.One hundred and eighty-six patients (38%) developed AKI. Seventy-nine (42%) had severe AKI and 27 (15%) required kidney replacement therapy. Fluid overload was common in all groups and 67% of those with severe AKI had > 10% fluid overload. Nephrology was consulted in less than 50% of those with severe AKI. In multivariable analysis, risk of severe AKI was lower in those taking a calcineurin inhibitor (CNI). Risk of death was higher in severe AKI compared to no AKI (RR 4.6, 95% CI 2.6-8.1).AKI and fluid overload are common in pediatric patients after HCT. Severe AKI occurred less often with CNI use and was associated with higher mortality. Future interventions to reduce AKI and its associated complications such as fluid overload are approaches to reducing morbidity and mortality after HCT. A higher resolution version of the Graphical abstract is available as Supplementary information.

  View details for DOI 10.1007/s00467-022-05731-x

  View details for Web of Science ID 000855595100002

  View details for PubMedID 36125547

  View details for PubMedCentralID 6376282

• 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

• Olfactomedin 4 as a novel loop of Henle-specific acute kidney injury biomarker PHYSIOLOGICAL REPORTS Hasson, D. C., Krallman, K., VanDenHeuvel, K., Menon, S., Piraino, G., Devarajan, P., Goldstein, S. L., Alder, M. N. 2022; 10 (18): e15453

  Abstract

  Acute kidney injury (AKI) is associated with morbidity and mortality. Urinary biomarkers may disentangle its clinical heterogeneity. Olfactomedin 4 (OLFM4) is a secreted glycoprotein expressed in stressed neutrophils and epithelial cells. In septic mice, OLFM4 expression localized to the kidney's loop of Henle (LOH) and was detectable in the urine. We hypothesized that urine OLFM4 (uOLFM4) will be increased in patients with AKI and sepsis. Urine from critically ill pediatric patients was obtained from a prospective study based on AKI and sepsis status. uOLFM4 was quantified with a Luminex immunoassay. AKI was defined by KDIGO severe criteria. Sepsis status was extracted from the medical record based on admission diagnosis. Immunofluorescence on pediatric kidney biopsies was performed with NKCC2, uromodulin and OLFM4 specific antibodies. Eight patients had no sepsis, no AKI; 7 had no sepsis but did have AKI; 10 had sepsis, no AKI; 11 had sepsis and AKI. Patients with AKI had increased uOLFM4 compared to no/stage 1 AKI (p = 0.044). Those with sepsis had increased uOLFM4 compared to no sepsis (p = 0.026). uOLFM4 and NGAL were correlated (r2 0.59, 95% CI 0.304-0.773, p = 0.002), but some patients had high uOLFM4 and low NGAL, and vice versa. Immunofluorescence on kidney biopsies demonstrated OLFM4 colocalization with NKCC2 and uromodulin, suggesting expression in the thick ascending LOH (TALH). We conclude that AKI and sepsis are associated with increased uOLFM4. uOLFM4 and NGAL correlated in many patients, but was poor in others, suggesting these markers may differentiate AKI subgroups. Given OLFM4 colocalization to human TALH, we propose OLFM4 may be a LOH-specific AKI biomarker.

  View details for DOI 10.14814/phy2.15453

  View details for Web of Science ID 000854967500001

  View details for PubMedID 36117416

  View details for PubMedCentralID PMC9483618

• Documentation of acute kidney injury at discharge from the neonatal intensive care unit and role of nephrology consultation JOURNAL OF PERINATOLOGY Chmielewski, J., Chaudhry, P. M., Harer, M. W., Menon, S., South, A. M., Chappell, A., Griffin, R., Askenazi, D., Jetton, J., Starr, M. C., Neonatal Kidney Collaborative 2022; 42 (7): 930-936

  Abstract

  To investigate whether NICU discharge summaries documented neonatal AKI and estimate if nephrology consultation mediated this association.Secondary analysis of AWAKEN multicenter retrospective cohort.AKI severity and diagnostic criteria.AKI documentation on NICU discharge summaries using multivariable logistic regression to estimate associations and test for causal mediation.Among 605 neonates with AKI, 13% had documented AKI. Those with documented AKI were more likely to have severe AKI (70.5% vs. 51%, p < 0.001) and SCr-only AKI (76.9% vs. 50.1%, p = 0.04). Nephrology consultation mediated 78.0% (95% CL 46.5-109.4%) of the total effect of AKI severity and 82.8% (95% CL 70.3-95.3%) of the total effect of AKI diagnostic criteria on documentation.We report a low prevalence of AKI documentation at NICU discharge. AKI severity and SCr-only AKI increased odds of AKI documentation. Nephrology consultation mediated the associations of AKI severity and diagnostic criteria with documentation.

  View details for DOI 10.1038/s41372-022-01424-3

  View details for Web of Science ID 000807923600001

  View details for PubMedID 35676535

  View details for PubMedCentralID PMC9280854

• Improving acute kidney injury diagnostic precision using biomarkers PRACTICAL LABORATORY MEDICINE Hasson, D., Menon, S., Gist, K. M. 2022; 30: e00272

  Abstract

  Acute kidney injury (AKI) is common in hospitalized patients of all ages and is associated with significant morbidity and mortality. Accurate prediction and early identification of AKI is of utmost importance because no therapy exists to mitigate AKI once it has occurred. Yet, serum creatinine lacks adequate sensitivity and specificity, and quantification of urine output is challenging in incontinent children without indwelling bladder catheters. Integration of clinically available biomarkers have the potential to delineate unique AKI phenotypes that could have important prognostic and therapeutic implications. Plasma Cystatin C, urine neutrophil gelatinase associated lipocalin (NGAL) and the urinary product of tissue inhibitor metalloproteinase (TIMP-2) and insulin growth factor binding protein-7 (IGFBP7) are clinically available. These biomarkers have been studied in heterogenous populations across the age spectrum and in a variety of clinical settings for prediction of AKI. The purpose of this review is to describe and discuss the clinically available AKI biomarkers including how they have been used to delineate AKI phenotypes.

  View details for DOI 10.1016/j.plabm.2022.e00272

  View details for Web of Science ID 000798143000002

  View details for PubMedID 35494424

  View details for PubMedCentralID PMC9046880

• Acute kidney injury in pediatric hematopoietic cell transplantation: critical appraisal and consensus PEDIATRIC NEPHROLOGY Raina, R., Abu-Arja, R., Sethi, S., Dua, R., Chakraborty, R., Dibb, J. T., Basu, R. K., Bissler, J., Felix, M., Brophy, P., Bunchman, T., Alhasan, K., Haffner, D., Kim, Y., Licht, C., McCulloch, M., Menon, S., Onder, A., Khooblall, P., Khooblall, A., Polishchuk, V., Rangarajan, H., Sultana, A., Kashtan, C. 2022; 37 (6): 1179-1203

  Abstract

  Hematopoietic cell transplantation (HCT) is a common therapy for the treatment of neoplastic and metabolic disorders, hematological diseases, and fatal immunological deficiencies. HCT can be subcategorized as autologous or allogeneic, with each modality being associated with their own benefits, risks, and post-transplant complications. One of the most common complications includes acute kidney injury (AKI). However, diagnosing HCT patients with AKI early on remains quite difficult. Therefore, this evidence-based guideline, compiled by the Pediatric Continuous Renal Replacement Therapy (PCRRT) working group, presents the various factors that contribute to AKI and recommendations regarding optimization of therapy with minimal complications in HCT patients.

  View details for DOI 10.1007/s00467-022-05448-x

  View details for Web of Science ID 000769549400002

  View details for PubMedID 35224659

  View details for PubMedCentralID 4102707

• Artificial Intelligence for AKI!Now: Let?s Not Await Plato?s Utopian Republic KIDNEY360 Soranno, D. E., Bihorac, A., Goldstein, S. L., Kashani, K. B., Menon, S., Nadkarni, G. N., Neyra, J. A., Pannu, N., Singh, K., Cerda, J., Koyner, J. L., AKI Artificial Intelligence W 2022; 3 (2): 376-381

  View details for DOI 10.34067/KID.0003472021

  View details for Web of Science ID 000913726700023

  View details for PubMedID 35373136

  View details for PubMedCentralID PMC8967630

• SARS-CoV-2 infection increases risk of acute kidney injury in a bimodal age distribution. BMC nephrology Bjornstad, E. C., Cutter, G., Guru, P., Menon, S., Aldana, I., House, S., M Tofil, N., St Hill, C. A., Tarabichi, Y., Banner-Goodspeed, V. M., Christie, A. B., Mohan, S. K., Sanghavi, D., Mosier, J. M., Vadgaonkar, G., Walkey, A. J., Kashyap, R., Kumar, V. K., Bansal, V., Boman, K., Sharma, M., Bogojevic, M., Deo, N., Retford, L., Gajic, O., Gist, K. M. 2022; 23 (1): 63

  Abstract

  Hospitalized patients with SARS-CoV2 develop acute kidney injury (AKI) frequently, yet gaps remain in understanding why adults seem to have higher rates compared to children. Our objectives were to evaluate the epidemiology of SARS-CoV2-related AKI across the age spectrum and determine if known risk factors such as illness severity contribute to its pattern.Secondary analysis of ongoing prospective international cohort registry. AKI was defined by KDIGO-creatinine only criteria. Log-linear, logistic and generalized estimating equations assessed odds ratios (OR), risk differences (RD), and 95% confidence intervals (CIs) for AKI and mortality adjusting for sex, pre-existing comorbidities, race/ethnicity, illness severity, and clustering within centers. Sensitivity analyses assessed different baseline creatinine estimators.Overall, among 6874 hospitalized patients, 39.6% (n = 2719) developed AKI. There was a bimodal distribution of AKI by age with peaks in older age (≥60 years) and middle childhood (5-15 years), which persisted despite controlling for illness severity, pre-existing comorbidities, or different baseline creatinine estimators. For example, the adjusted OR of developing AKI among hospitalized patients with SARS-CoV2 was 2.74 (95% CI 1.66-4.56) for 10-15-year-olds compared to 30-35-year-olds and similarly was 2.31 (95% CI 1.71-3.12) for 70-75-year-olds, while adjusted OR dropped to 1.39 (95% CI 0.97-2.00) for 40-45-year-olds compared to 30-35-year-olds.SARS-CoV2-related AKI is common with a bimodal age distribution that is not fully explained by known risk factors or confounders. As the pandemic turns to disproportionately impacting younger individuals, this deserves further investigation as the presence of AKI and SARS-CoV2 infection increases hospital mortality risk.

  View details for DOI 10.1186/s12882-022-02681-2

  View details for PubMedID 35144572

  View details for PubMedCentralID PMC8831033

• Major adverse kidney events after acute kidney injury in the pediatric intensive care unit: a propensity score-matched cohort study PEDIATRIC NEPHROLOGY Kula, A. J., Qu, P., Strub, B., Smith, J. M., Menon, S. 2022; 37 (9): 2099-2107

  Abstract

  Acute kidney injury (AKI) in patients admitted to the pediatric intensive care unit (PICU) is associated with poor short-term and long-term outcomes. Greater awareness of long-term AKI-associated outcomes is needed to optimally plan follow-up and management after ICU discharge. We used propensity score methods to study associations between pediatric AKI and major adverse kidney outcomes, including mortality.We included all children 6 months-18 years admitted to PICU at Seattle Children's Hospital from 7/1/2009 to 12/31/2018. Our primary outcome measure was Major Adverse Kidney Events at 30 days (MAKE30): creatinine > 200% of baseline, eGFR < 60 mL/min/1.73 m2, dialysis dependence, or mortality. Propensity scores for AKI development in PICU were generated using demographic, medical history, admission, and PICU hospitalization variables. Patients with AKI were matched to control patients without AKI. Logistic regression was used to test association between AKI status and MAKE30.In the unmatched cohort (n = 878), patients with AKI had lower platelet count (160 vs. 222) and higher PRISM III score (11 vs. 3.5). After propensity score matching, those with AKI vs. no AKI had similar PRISM III scores (9 vs. 10) and platelet count (163 vs. 159). AKI was significantly associated with MAKE30 after propensity score matching (OR: 2.97; 95% CI 1.82-4.84).Propensity score matching significantly reduced imbalance in baseline characteristics between those with and without AKI. After matching, AKI remained significantly associated with MAKE30. Patients who developed AKI were more likely to have abnormal kidney function at 30 and 90 days after ICU admission and may be at high risk for developing CKD in the future. A higher resolution version of the Graphical abstract is available as Supplementary information.

  View details for DOI 10.1007/s00467-021-05348-6

  View details for Web of Science ID 000744932600001

  View details for PubMedID 35041037

• Characterization and Outcomes of Hospitalized Children With Coronavirus Disease 2019: A Report From a Multicenter, Viral Infection and Respiratory Illness Universal Study (Coronavirus Disease 2019) Registry CRITICAL CARE MEDICINE Bhalala, U. S., Gist, K. M., Tripathi, S., Boman, K., Kumar, V. K., Retford, L., Chiotos, K., Blatz, A. M., Dapul, H., Verma, S., Sayed, I. A., Gharpure, V. P., Bjornstad, E., Tofil, N., Irby, K., Sanders, R. C., Heneghan, J. A., Thomas, M., Gupta, M. K., Oulds, F. E., Arteaga, G. M., Levy, E. R., Gupta, N., Kaufman, M., Abdelaty, A., Shlomovich, M., Medar, S. S., O'Meara, A., Kuehne, J., Menon, S., Khandhar, P. B., Miller, A. S., Barry, S. M., Danesh, V. C., Khanna, A. K., Zammit, K., Stulce, C., McGonagill, P. W., Bercow, A., Amzuta, I. G., Gupta, S., Almazyad, M. A., Pierre, L., Sendi, P., Ishaque, S., Anderson, H. L., Nawathe, P., Akhter, M., Lyons, P. G., Chen, C., Walkey, A. J., Bihorac, A., Bello, I., Ben Ari, J., Kovacevic, T., Bansal, V., Brinton, J. T., Zimmerman, J. J., Kashyap, R., Soc Critical Care Med Discovery Vi 2022; 50 (1): E40-E51

  Abstract

  Multicenter data on the characteristics and outcomes of children hospitalized with coronavirus disease 2019 are limited. Our objective was to describe the characteristics, ICU admissions, and outcomes among children hospitalized with coronavirus disease 2019 using Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study: Coronavirus Disease 2019 registry.Retrospective study.Society of Critical Care Medicine Viral Infection and Respiratory Illness Universal Study (Coronavirus Disease 2019) registry.Children (< 18 yr) hospitalized with coronavirus disease 2019 at participating hospitals from February 2020 to January 2021.None.The primary outcome was ICU admission. Secondary outcomes included hospital and ICU duration of stay and ICU, hospital, and 28-day mortality. A total of 874 children with coronavirus disease 2019 were reported to Viral Infection and Respiratory Illness Universal Study registry from 51 participating centers, majority in the United States. Median age was 8 years (interquartile range, 1.25-14 yr) with a male:female ratio of 1:2. A majority were non-Hispanic (492/874; 62.9%). Median body mass index (n = 817) was 19.4 kg/m2 (16-25.8 kg/m2), with 110 (13.4%) overweight and 300 (36.6%) obese. A majority (67%) presented with fever, and 43.2% had comorbidities. A total of 238 of 838 (28.2%) met the Centers for Disease Control and Prevention criteria for multisystem inflammatory syndrome in children, and 404 of 874 (46.2%) were admitted to the ICU. In multivariate logistic regression, age, fever, multisystem inflammatory syndrome in children, and pre-existing seizure disorder were independently associated with a greater odds of ICU admission. Hospital mortality was 16 of 874 (1.8%). Median (interquartile range) duration of ICU (n = 379) and hospital (n = 857) stay were 3.9 days (2-7.7 d) and 4 days (1.9-7.5 d), respectively. For patients with 28-day data, survival was 679 of 787, 86.3% with 13.4% lost to follow-up, and 0.3% deceased.In this observational, multicenter registry of children with coronavirus disease 2019, ICU admission was common. Older age, fever, multisystem inflammatory syndrome in children, and seizure disorder were independently associated with ICU admission, and mortality was lower among children than mortality reported in adults.

  View details for DOI 10.1097/CCM.0000000000005232

  View details for Web of Science ID 000730780000008

  View details for PubMedID 34387240

  View details for PubMedCentralID PMC8670078

• The Pediatric Nephrology Workforce Crisis: A Call to Action JOURNAL OF PEDIATRICS Ashoor, I., Weidemann, D., Elenberg, E., Halbach, S., Harshman, L., Kula, A., Mahan, J. D., Nada, A., Quiroga, A., Mahon, A., Smith, J., Somers, M., Brophy, P. D., ASPN Workforce Summit Action Grp 2021; 239: 5-+

  View details for DOI 10.1016/j.jpeds.2021.03.033

  View details for Web of Science ID 000719251000001

  View details for PubMedID 33798511

• The Impact of Obesity on Disease Severity and Outcomes Among Hospitalized Children With COVID-19. Hospital pediatrics Tripathi, S., Christison, A. L., Levy, E., McGravery, J., Tekin, A., Bolliger, D., Kumar, V. K., Bansal, V., Chiotos, K., Gist, K. M., Dapul, H. R., Bhalala, U. S., Gharpure, V. P., Heneghan, J. A., Gupta, N., Bjornstad, E. C., Montgomery, V. L., Walkey, A., Kashyap, R., Arteaga, G. M. 2021; 11 (11): e297-e316

  Abstract

  To describe the impact of obesity on disease severity and outcomes of coronavirus disease 2019 (COVID-19) among hospitalized children.This retrospective cohort study from the Society of Critical Care Medicine Viral Respiratory Illness Universal Study registry included all children hospitalized with COVID-19 from March 2020 to January 2021. Obesity was defined by Centers for Disease Control and Prevention BMI or World Health Organization weight for length criteria. Critical illness definition was adapted from National Institutes of Health criteria of critical COVID. Multivariate mixed logistic and linear regression was performed to calculate the adjusted odds ratio of critical illness and the adjusted impact of obesity on hospital length of stay.Data from 795 patients (96.4% United States) from 45 sites were analyzed, including 251 (31.5%) with obesity and 544 (68.5%) without. A higher proportion of patients with obesity were adolescents, of Hispanic ethnicity, and had other comorbidities. Those with obesity were also more likely to be diagnosed with multisystem inflammatory syndrome in children (35.7% vs 28.1%, P = .04) and had higher ICU admission rates (57% vs 44%, P < .01) with more critical illness (30.3% vs 18.3%, P < .01). Obesity had more impact on acute COVID-19 severity than on multisystem inflammatory syndrome in children presentation. The adjusted odds ratio for critical illness with obesity was 3.11 (95% confidence interval: 1.8-5.3). Patients with obesity had longer adjusted length of stay (exponentiated parameter estimate 1.3; 95% confidence interval: 1.1-1.5) compared with patients without obesity but did not have increased mortality risk due to COVID-19 (2.4% vs 1.5%, P = .38).In a large, multicenter cohort, a high proportion of hospitalized children from COVID-19 had obesity as comorbidity. Furthermore, obesity had a significant independent association with critical illness.

  View details for DOI 10.1542/hpeds.2021-006087

  View details for PubMedID 34168067

• Liberation From Continuous Renal Replacement Therapy: Does It Have an Impact on Short-term Outcomes? MAYO CLINIC PROCEEDINGS Gist, K. M., Menon, S. 2021; 96 (11): 2743-2745

  View details for DOI 10.1016/j.mayocp.2021.09.010

  View details for Web of Science ID 000714983600004

  View details for PubMedID 34736605

• Practice patterns and outcomes of maintenance dialysis in children < 2 years of age: a report of the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) PEDIATRIC NEPHROLOGY Yu, E. D., Galbiati, S., Munshi, R., Smith, J. M., Menon, S., NAPRTCS Investigators 2022; 37 (5): 1117-1124

  Abstract

  Peritoneal dialysis (PD) is the preferred mode of kidney replacement therapy (KRT) in infants and young children with kidney failure. Hemodialysis (HD) is used less often due to the technical challenges and risk of complications in smaller patients. There are limited data on chronic HD in this patient population.This was a retrospective study of children younger than 24 months on HD and PD in the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) registry between January 1992 and December 2018. We compared demographic, clinical, and laboratory data and outcomes, including patient survival and kidney transplantation.We identified 1125 infants and toddlers younger than 2 years of age who initiated KRT from January 1992 to December 2018. Of those, 1011 (89.8%) initiated peritoneal dialysis and 114 (10.2%) initiated hemodialysis. Median (IQR) age at HD onset was 12 (5.6-18.7) months compared to 4.6 (0.8-11.7) months at PD onset (p < 0.001). The primary cause of kidney failure with replacement therapy was congenital anomalies of the kidney and urinary tract (56.2% of PD versus 39.5% of HD group). Patients on HD had superior growth and nutrition markers than those on PD. Patient survival was similar between the two groups.While HD may not be the modality of choice for chronic KRT in younger children, 10% of children younger than 24 months of age receive maintenance HD and the numbers have increased over time. Patient survival on dialysis is similar irrespective of dialysis modality. A higher resolution version of the Graphical abstract is available as Supplementary information.

  View details for DOI 10.1007/s00467-021-05287-2

  View details for Web of Science ID 000707293400003

  View details for PubMedID 34648058

• Utility of Kinetic GFR for Predicting Severe Persistent AKI in Critically Ill Children and Young Adults KIDNEY360 Menon, S., Basu, R. K., Barhight, M. F., Goldstein, S. L., Gist, K. M. 2021; 2 (5): 869-872

  Abstract

  Kinetic eGFR can be part of a multidimensional approach for AKI prediction combined with biomarkers, fluid corrected creatinine, and renal angina.Kinetic eGFR on day 1 is not independently associated with severe day-3 AKI in children and young adults who are critically ill.

  View details for DOI 10.34067/KID.0006892020

  View details for Web of Science ID 000860655700011

  View details for PubMedID 35373066

  View details for PubMedCentralID PMC8791351

• For Whom the Bell Tolls: Acute Kidney Injury and Electronic Alerts for the Pediatric Nephrologist FRONTIERS IN PEDIATRICS Nguyen, E. D., Menon, S. 2021; 9: 628096

  Abstract

  With the advent of the electronic medical record, automated alerts have allowed for improved recognition of patients with acute kidney injury (AKI). Pediatric patients have the opportunity to benefit from such alerts, as those with a diagnosis of AKI are at risk of developing long-term consequences including reduced renal function and hypertension. Despite extensive studies on the implementation of electronic alerts, their overall impact on clinical outcomes have been unclear. Understanding the results of these studies have helped define best practices in developing electronic alerts with the aim of improving their impact on patient care. As electronic alerts for AKI are applied to pediatric patients, identifying their strengths and limitations will allow for continued improvement in its use and efficacy.

  View details for DOI 10.3389/fped.2021.628096

  View details for Web of Science ID 000643688400001

  View details for PubMedID 33912520

  View details for PubMedCentralID PMC8072003

• Neonatal acute kidney injury: a case-based approach PEDIATRIC NEPHROLOGY Starr, M. C., Menon, S. 2021; 36 (11): 3607-3619

  Abstract

  Neonatal acute kidney injury (AKI) is increasingly recognized as a common complication in critically ill neonates. Over the last 5-10 years, there have been significant advancements which have improved our understanding and ability to care for neonates with kidney disease. A variety of factors contribute to an increased risk of AKI in neonates, including decreased nephron mass and immature tubular function. Multiple factors complicate the diagnosis of AKI including low glomerular filtration rate at birth and challenges with serum creatinine as a marker of kidney function in newborns. AKI in neonates is often multifactorial, but the cause can be identified with careful diagnostic evaluation. The best approach to treatment in such patients may include diuretic therapies or kidney support therapy. Data for long-term outcomes are limited but suggest an increased risk of chronic kidney disease (CKD) and hypertension in these infants. We use a case-based approach throughout this review to illustrate these concepts and highlight important evidence gaps in the diagnosis and management of neonatal AKI.

  View details for DOI 10.1007/s00467-021-04977-1

  View details for Web of Science ID 000618606200001

  View details for PubMedID 33594463

  View details for PubMedCentralID 19082634

• Early Career Investigator: Biocommentary PEDIATRIC RESEARCH Menon, S. 2021; 89 (5): 1051

  View details for DOI 10.1038/s41390-020-01361-x

  View details for Web of Science ID 000609126300020

  View details for PubMedID 33469178

• Coronavirus Disease 2019-Associated PICU Admissions: A Report From the Society of Critical Care Medicine Discovery Network Viral Infection and Respiratory Illness Universal Study Registry. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies Tripathi, S., Gist, K. M., Bjornstad, E. C., Kashyap, R., Boman, K., Chiotos, K., Gharpure, V. P., Dapul, H., Sayed, I. A., Kuehne, J., Heneghan, J. A., Gupta, M., Khandhar, P. B., Menon, S., Gupta, N., Kumar, V. K., Retford, L., Zimmerman, J., Bhalala, U. S. 2021; 22 (7): 603-615

  Abstract

  To compare clinical characteristics and outcomes of children admitted to the PICU for severe acute respiratory syndrome coronavirus 2-related illness with or without multisystem inflammatory syndrome in children. The secondary objective was to identify explanatory factors associated with outcome of critical illness defined by a composite index of in-hospital mortality and organ system support requirement.Retrospective cohort study.Thirty-eight PICUs within the Viral Infection and Respiratory Illness Universal Study registry from March 2020 to January 2021.Children less than 18 years with severe acute respiratory syndrome coronavirus 2-related illness with or without multisystem inflammatory syndrome in children.Of 394 patients, 171 (43.4%) had multisystem inflammatory syndrome in children. Children with multisystem inflammatory syndrome in children were more likely younger (2-12 yr vs adolescents; p < 0.01), Black (35.6% vs 21.9%; p < 0.01), present with fever/abdominal pain than cough/dyspnea (p < 0.01), and less likely to have comorbidities (33.3% vs 61.9%; p < 0.01) compared with those without multisystem inflammatory syndrome in children. Inflammatory marker levels, use of inotropes/vasopressors, corticosteroids, and anticoagulants were higher in multisystem inflammatory syndrome in children patients (p < 0.01). Overall mortality was 3.8% (15/394), with no difference in the two groups. Diagnosis of multisystem inflammatory syndrome in children was associated with longer duration of hospitalization as compared to nonmultisystem inflammatory syndrome in children (7.5 d[interquartile range, 5-11] vs 5.3 d [interquartile range, 3-11 d]; p < 0.01). Critical illness occurred in 164 patients (41.6%) and was more common in patients with multisystem inflammatory syndrome in children compared with those without (55.6% vs 30.9%; p < 0.01). Multivariable analysis failed to show an association between critical illness and age, race, sex, greater than or equal to three signs and symptoms, or greater than or equal to two comorbidities among the multisystem inflammatory syndrome in children cohort. Among nonmultisystem inflammatory syndrome in children patients, the presence of greater than or equal to two comorbidities was associated with greater odds of critical illness (odds ratio 2.95 [95% CI, 1.61-5.40]; p < 0.01).This study delineates significant clinically relevant differences in presentation, explanatory factors, and outcomes among children admitted to PICU with severe acute respiratory syndrome coronavirus 2-related illness stratified by multisystem inflammatory syndrome in children.

  View details for DOI 10.1097/PCC.0000000000002760

  View details for PubMedID 33965987

  View details for PubMedCentralID PMC8240492

• Timing of Fluid Overload and Association With Patient Outcome PEDIATRIC CRITICAL CARE MEDICINE Lima, L., Menon, S., Goldstein, S. L., Basu, R. K. 2021; 22 (1): 114-124

  Abstract

  To determine if the timing of excess fluid accumulation (fluid overload) is associated with adverse patient outcomes.Secondary analysis of a prospectively collected dataset.PICU of a tertiary care hospital.Children 3 months to 25 years old admitted to the PICU with expected length of stay greater than or equal to 48 hours.Patients were dichotomized by time of peak overload: peak fluid overload from ICU admission (Day0) to 48 hours (Day3-7) and peak fluid overload value after 48 hours of ICU admission, as well as time of first-time negative daily fluid balance: net fluid out greater than net fluid in for that 24-hour period.There were 177 patients who met inclusion criteria, 92 (52%) male, with an overall mortality rate of 7% (n = 12). There were no differences in severity of illness scores or fluid overload on Day0 between peak fluid overload from ICU admission (Day0) to 48 hours (Day3-7) (n = 97; 55%) and peak fluid overload value after 48 hours of ICU admission (n = 80; 45%) groups. Peak fluid overload value after 48 hours of ICU admission was associated with a longer median ICU course (8 [4-15] vs 4 d [3-8 d]; p ≤ 0.001], hospital length of stay (18 [10-38) vs 12 [8-24]; p = 0.01], and increased risk of mortality (n = 10 [13%] vs 2 [2%]; χ2 = 7.6; p = 0.006]. ICU length of stay was also longer in the peak fluid overload value after 48 hours of ICU admission group when only patients with at least 7 days of ICU stay were analyzed (p = 0.02). Timing of negative fluid balance was also correlated with outcome. Compared with Day0-2, a negative daily fluid balance on Day3-7 was associated with increased length of mechanical ventilation (3 [1-7] vs 1 d [2-10 d]; p ≤ 0.001) and increased hospital (17 [10-35] vs 11 d [7-26 d]; p = 0.006) and ICU (7 [4-13] vs 4 d [3-7 d]; p ≤ 0.001) length of stay compared with a negative fluid balance between Day0-2.Our results show timing of fluid accumulation not just peak percentage accumulated is associated with patient outcome. Further exploration of the association between time and fluid accumulation is warranted.

  View details for DOI 10.1097/PCC.0000000000002547

  View details for Web of Science ID 000639305400024

  View details for PubMedID 32947381

• The impact of increased awareness of acute kidney injury in the Neonatal Intensive Care Unit on acute kidney injury incidence and reporting: results of a retrospective cohort study JOURNAL OF PERINATOLOGY Starr, M. C., Kula, A., Lieberman, J., Menon, S., Perkins, A. J., Lam, T., Chabra, S., Hingorani, S. 2020; 40 (9): 1301-1307

  Abstract

  To evaluate the impact of nephrology integration in the NICU on acute kidney injury (AKI) incidence, provider reporting, and nephrology referral.Cohort study in a single-center NICU from January 2012 to December 2017 (n = 1464). We assessed the impact of clinical practice changes including neonatal-nephrology rounds on the incidence of AKI.AKI occurred in 318 neonates (22%). AKI occurred less frequently in those admitted after clinical practice changes (P < 0.001). After multivariable adjustment, clinical practice changes were associated with reduced odds of AKI (adjusted odds ratio, 0.31; 95% CI 0.22-0.44, P < 0.001). Provider reporting of AKI improved (P < 0.001) and more neonates were referred for nephrology follow-up (P < 0.001).Increased nephrology integration in the NICU was associated with decreased AKI incidence. While recognition of AKI improved, AKI remained poorly reported and nephrology AKI follow-up did not routinely occur. This study supports the importance of increased nephrology involvement in the NICU.

  View details for DOI 10.1038/s41372-020-0725-y

  View details for Web of Science ID 000549690400001

  View details for PubMedID 32681064

  View details for PubMedCentralID PMC7442645

• Impact of integrated clinical decision support systems in the management of pediatric acute kidney injury: a pilot study PEDIATRIC RESEARCH Menon, S., Tarrago, R., Carlin, K., Wu, H., Yonekawa, K. 2021; 89 (5): 1164-1170

  Abstract

  Acute kidney injury (AKI) is common but not often recognized. Early recognition and management may improve patient outcomes.This is a prospective, nonrandomized study of clinical decision support (CDS) system [combining electronic alert and standardized care pathway (SCP)] to evaluate AKI detection and progression in hospitalized children. The study was done in three phases: pre-, intervention (CDS) and post. During CDS, text-page with AKI stage and link to SCP was sent to patient's contact provider at diagnosis of AKI using creatinine. The SCP provided guidelines on AKI management [AEIOU: Assess cause of AKI, Evaluate drug doses, Intake-Output charting, Optimize volume status, Urine dipstick].In all, 239 episodes of AKI in 225 patients (97 females, 43.1%) were analyzed. Proportion of patients with decrease in the stage of AKI after onset was 71.4% for CDS vs. 64.4% for pre- and 55% for post-CDS phases (p = 0.3). Documentation of AKI was higher during CDS (74.3% CDS vs. 47.5% pre- and 57.5% post-, p < 0.001). Significantly greater proportion of patients had nephrotoxic medications adjusted, or fluid plan changed during CDS. Patients from CDS phase had higher eGFR at discharge and at follow-up.AKI remains under-recognized. CDS (electronic alerts and SCP) improve recognition and allow early intervention. This may improve long-term outcomes, but larger studies are needed.Acute kidney injury can cause significant morbidity and mortality. It is under-recognized in children. Clinical decision support can be used to leverage existing data in the electronic health record to improve AKI recognition. This study demonstrates the use of a novel, electronic health record-linked, clinical decision support tool to improve the recognition of AKI and guideline-adherent clinical care.

  View details for DOI 10.1038/s41390-020-1046-8

  View details for Web of Science ID 000546215500001

  View details for PubMedID 32620006

• Acute kidney injury and chronic kidney disease after non-kidney solid organ transplantation PEDIATRIC TRANSPLANTATION Menon, S., Pollack, A. H., Sullivan, E., Murphy, T., Smith, J. 2020; 24 (6): e13753

  Abstract

  SOT is the treatment of choice for end-stage organ disease. Improved long-term survival after NKSOT has uncovered chronic morbidity including CKD. AKI is common after NKSOT and may be associated with long-term CKD.We performed a retrospective cohort study looking at AKI and CKD after pediatric heart (n = 109) or liver (n = 112) transplant. AKI was defined using KDIGO creatinine-based criteria. pAKI was AKI ≤ 7 days post-transplant; CKD3-5 was eGFR < 60 mL/min/1.73 m2 by modified Schwartz formula for > 3 months. We looked at the incidence of CKD3-5 and the effect of perioperative pAKI on the slope of eGFR post-transplant.pAKI was seen in 63% (n = 69) after heart and 38% (n = 43) after liver transplant. pAKI was associated with longer ICU and hospital stays. Cumulative incidence (95% CI) of CKD3-5 at 60 months post-heart transplant was 40.9% (27.9%-57.1%) in patients with AKI vs 35.8% (17.1%-64.8%) in those without (P = NS). Post-liver transplant, the cumulative incidence of CKD3-5 at 60 months was 0% in those without pAKI vs 10% (3.2%-29.3%) in those with (P = .01). Patients with pAKI had lower eGFR at last follow-up.pAKI and CKD are common after NKSOT. Incidence of CKD is higher in those with pAKI. AKI episodes are associated with a drop in eGFR during follow-up. Identifying patients who have had AKI is an important first step in identifying those at risk of repeated AKI episodes. These patients would benefit from closer monitoring for CKD, lower nephrotoxic drug use, and follow-up with nephrology.

  View details for DOI 10.1111/petr.13753

  View details for Web of Science ID 000537592700001

  View details for PubMedID 32497381

• Assessment of the Independent and Synergistic Effects of Fluid Overload and Acute Kidney Injury on Outcomes of Critically Ill Children* PEDIATRIC CRITICAL CARE MEDICINE Gist, K. M., Selewski, D. T., Brinton, J., Menon, S., Goldstein, S. L., Basu, R. K. 2020; 21 (2): 170-177

  Abstract

  Evaluate the independent and synergistic associations of fluid overload and acute kidney injury with outcome in critically ill pediatric patients.Secondary analysis of the Acute Kidney Injury in Children Expected by Renal Angina and Urinary Biomarkers (NCT01735162) prospective observational study.Single-center quaternary level PICU.One-hundred forty-nine children 3 months to 25 years old with predicted PICU length of stay greater than 48 hours, and an indwelling urinary catheter enrolled (September 2012 to March 2014). Acute kidney injury (defined by creatinine or urine output on day 3) and fluid overload (≥ 20% on day 3) were used as outcome variables and risk factors for ICU endpoints assessed at 28 days.None.Acute kidney injury and fluid overload occurred in 19.4% and 24.2% respectively. Both acute kidney injury and fluid overload were associated with longer ICU length of stay but neither maintained significance after multivariate regression. Delineation into unique fluid overload/acute kidney injury classifications demonstrated that fluid overload patients experienced a longer ICU and hospital length of stay and higher rate of mortality compared with fluid overload patients, regardless of acute kidney injury status. Fluid overload/acute kidney injury patients had increased odds of death (p = 0.013). After correction for severity of illness, ICU length of stay remained significantly longer in fluid overload/acute kidney injury patients compared with patients without both classifications (17.4; 95% CI, 11.0-23.7 vs 8.8; 95% CI, 7.3-10.9; p = 0.05). Correction of acute kidney injury classification for net fluid balance led to acute kidney injury class switching in 29 patients and strengthened the association with increased mechanical ventilation and ICU length of stay on bivariate analysis, but reduced the increased risk conferred by fluid overload for mortality.The current study suggests the effects of significant fluid accumulation may be delineable from the effects of acute kidney injury. Concurrent fluid overload and acute kidney injury significantly worsen outcome. Correction of acute kidney injury assessment for net fluid balance may refine diagnosis and unmask acute kidney injury associated with deleterious downstream sequelae. The unique effects of fluid overload and acute kidney injury on outcome in critically ill patients warrant further study.

  View details for DOI 10.1097/PCC.0000000000002107

  View details for Web of Science ID 000528892100014

  View details for PubMedID 31568240

  View details for PubMedCentralID PMC7007847

• Acute Kidney Injury and Bronchopulmonary Dysplasia in Premature Neonates Born Less than 32 Weeks' Gestation AMERICAN JOURNAL OF PERINATOLOGY Starr, M. C., Boohaker, L., Eldredge, L. C., Menon, S., Griffin, R., Mayock, D. E., Li, L., Askenazi, D., Hingorani, S., Neonatal Kidney Collaborative 2020; 37 (3): 341-348

  Abstract

  This study aimed to evaluate the association between acute kidney injury (AKI) and bronchopulmonary dysplasia (BPD) in infants born <32 weeks of gestational age (GA).Present study is a secondary analysis of premature infants born at <32 weeks of GA in the Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) retrospective cohort (n = 546). We stratified by gestational age and used logistic regression to determine association between AKI and moderate or severe BPD/mortality.Moderate or severe BPD occurred in 214 of 546 (39%) infants, while death occurred in 32 of 546 (6%); the composite of moderate or severe BPD/death occurred in 246 of 546 (45%). For infants born ≤29 weeks of gestation, the adjusted odds ratio (OR) of AKI and the primary outcome was 1.15 (95% confidence interval [CI] = 0.47-2.86; p = 0.76). Infants born between 29 and 32 weeks of gestation with AKI had four-fold higher odds of moderate or severe BPD/death that remained after controlling for multiple factors (adjusted OR = 4.21, 95% CI: 2.07-8.61; p < 0.001).Neonates born between 29 and 32 weeks who develop AKI had a higher likelihood of moderate or severe BPD/death than those without AKI. Further studies are needed to validate our findings and evaluate mechanisms of multiorgan injury.

  View details for DOI 10.1055/s-0039-3400311

  View details for Web of Science ID 000516614800016

  View details for PubMedID 31777046

  View details for PubMedCentralID PMC7409513

• Acute Kidney Injury is Associated with Poor Lung Outcomes in Infants Born ≥32 Weeks of Gestational Age AMERICAN JOURNAL OF PERINATOLOGY Starr, M. C., Boohaker, L., Eldredge, L. C., Menon, S., Griffin, R., Mayock, D., Askenazi, D., Hingorani, S., Ambalavanan, N., Selewski, D. T., Sarkar, S., Kent, A., Fletcher, J., Abitbol, C. L., DeFreitas, M., Duara, S., Charlton, J. R., Swanson, J. R., Guillet, R., D'Angio, C., Mian, A., Rademacher, E., Mhanna, M. J., Raina, R., Kumar, D., Jetton, J. G., Brophy, P. D., Colaizy, T. T., Klein, J. M., Arikan, A., Rhee, C. J., Goldstein, S. L., Nathan, A. T., Kupferman, J. C., Bhutada, A., Rastogi, S., Bonachea, E., Mahan, J., Cole, F., Davis, T., Dower, J., Milner, L., Smith, A., Fuloria, M., Reidy, K., Kaskel, F. J., Soranno, D. E., Gien, J., Gist, K. M., Chishti, A. S., Hanna, M. H., Wong, C. S., Joseph, C., DuPont, T., Ohls, R., Staples, A., Khokhar, S., Perazzo, S., Ray, P. E., Revenis, M., Sethi, S. K., Rohatgi, S., Mammen, C., Synnes, A., Wazir, S., Wintermark, P., Woroniecki, R., Sridhar, S., Ingraham, S., Nada, A., Zappitelli, M., Neonatal Kidney Collaborative 2020; 37 (2): 231-239

  Abstract

  This study aimed to evaluate the association between acute kidney injury (AKI) and lung outcomes in infants born ≥32 weeks of gestational age (GA).Secondary analysis of infants ≥32 weeks of GA in the assessment of worldwide acute kidney injury epidemiology in neonates (AWAKEN) retrospective cohort (n = 1,348). We used logistic regression to assess association between AKI and a composite outcome of chronic lung disease (CLD) or death at 28 days of age and linear regression to evaluate association between AKI and duration of respiratory support.CLD occurred in 82/1,348 (6.1%) infants, while death occurred in 22/1,348 (1.6%); the composite of CLD/death occurred in 104/1,348 (7.7%). Infants with AKI had an almost five-fold increased odds of CLD/death, which remained after controlling for GA, maternal polyhydramnios, multiple gestations, 5-minute Apgar's score, intubation, and hypoxic-ischemic encephalopathy (adjusted odds ratio [OR] = 4.9, 95% confidence interval [CI]: 3.2-7.4; p < 0.0001). Infants with AKI required longer duration of respiratory support (count ratio = 1.59, 95% CI: 1.14-2.23, p = 0.003) and oxygen (count ratio = 1.43, 95% CI: 1.22-1.68, p < 0.0001) compared with those without AKI.AKI is associated with CLD/death and longer duration of respiratory support in infants born at ≥32 weeks of GA. Further prospective studies are needed to elucidate the pathophysiologic relationship.

  View details for DOI 10.1055/s-0039-1698836

  View details for Web of Science ID 000507900100014

  View details for PubMedID 31739364

  View details for PubMedCentralID PMC7408289

• 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

• Kidney Support in Children using an Ultrafiltration Device A Multicenter, Retrospective Study CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Menon, S., Broderick, J., Munshi, R., Dill, L., DePaoli, B., Fathallah-Shaykh, S., Claes, D., Goldstein, S. L., Askenazi, D. J. 2019; 14 (10): 1432-1440

  Abstract

  Provision of kidney replacement therapy (KRT) to manage kidney injury and volume overload in critically ill neonates and small children is technically challenging. The use of machines designed for adult-sized patients, necessitates large catheters, a high extracorporeal volume relative to patient size, and need for blood priming. The Aquadex FlexFlow System (CHF Solutions Inc., Eden Prairie, MN) is an ultrafiltration device designed for fluid removal in adults with diuretic resistant heart failure. It has an extracorporeal volume of 33 ml, which can potentially mitigate some complications seen at onset of KRT in smaller infants.In this multicenter, retrospective case series of children who received KRT with an ultrafiltration device (n=119 admissions, 884 circuits), we report demographics, circuit characteristics, complications, and short- and long-term outcomes. Patients were grouped according to weight (<10, 10-20, and >20 kg), and received one of three modalities: slow continuous ultrafiltration, continuous venovenous hemofiltration (CVVH), or prolonged intermittent KRT. Our primary outcome was survival to end of KRT.Treatment patterns and outcomes varied between the groups. In patients who weighed <10 kg, the primary indication was AKI in 40%, volume overload in 46%, and ESKD in 14%. These patients primarily received CVVH (66%, n=48) and prolonged intermittent KRT (21%, n=15). In the group weighing >20 kg, volume overload was the primary indication in 91% and slow continuous ultrafiltration was the most common modality. Patients <10 kg had lower KRT survival than those >20 kg (60% versus 97%), more volume overload at onset, and received KRT for a longer duration. Cardiovascular complications at initiation were seen in 3% of treatments and none were severe. Complications during therapy were seen in 15% treatments and most were vascular access-related.We report the first pediatric experience using an ultrafiltration device to provide a range of therapies, including CVVH, prolonged intermittent KRT, and slow continuous ultrafiltration. We were able to initiate KRT with minimal complications, particularly in critically ill neonates. There is an unmet need for devices specifically designed for younger patients. Having size-appropriate machines will improve the care of smaller children who require kidney support.

  View details for DOI 10.2215/CJN.03240319

  View details for Web of Science ID 000497955900007

  View details for PubMedID 31462396

  View details for PubMedCentralID PMC6777586

• Integration of urinary neutrophil gelatinase-associated lipocalin with serum creatinine delineates acute kidney injury phenotypes in critically ill children JOURNAL OF CRITICAL CARE Stanski, N., Menon, S., Goldstein, S. L., Basu, R. K. 2019; 53: 1-7

  Abstract

  Acute kidney injury (AKI) is prevalent in critically ill patients and associated with poor outcomes. Current AKI diagnostics- changes to serum creatinine (SCr) and urine output- are imprecise. Integration of injury biomarkers with SCr may improve diagnostic precision.We performed a secondary analysis of a study of critically ill children. Measurements of urine neutrophil gelatinase-associated lipocalin (uNGAL) and SCr samples from ICU admission facilitated the creation of four groups for comparison, based on elevation of SCr from baseline and reference NGAL cut-off value: uNGAL-/SCr-, uNGAL+/SCr-, uNGAL-/SCr + and uNGAL+/SCr+. The primary outcome assessed was AKI severity on Day 3.178 children were studied. Compared to uNGAL-/SCr-, uNGAL+/SCr- patients had increased risk for all-stage Day 3 AKI (≥ KDIGO stage 1) (OR 3.83, [1.3-11.3], p = .025). Compared to uNGAL-/SCr+, uNGAL+/SCr + patients had increased risk for severe Day 3 AKI (≥ KDIGO stage 2) (OR 12, [1.4-102], p = .018). The only patients to suffer all-stage Day 3 AKI and mortality were uNGAL+ (3.2% uNGAL+/SCr-; 6.5% uNGAL+/SCr+).Unique biomarker combinations on admission are predictive of distinct Day 3 AKI severity phenotypes. These classifications may enable a more personalized approach to the early management of AKI. Expanded study in larger populations is warranted.

  View details for DOI 10.1016/j.jcrc.2019.05.017

  View details for Web of Science ID 000478566600001

  View details for PubMedID 31174170

• Blood-borne viral infections in pediatric hemodialysis PEDIATRIC NEPHROLOGY Menon, S., Munshi, R. 2019; 34 (6): 1019-1031

  Abstract

  Hemodialysis patients are at increased risk for development of blood-borne viral infections. Human immunodeficiency virus (HIV), a once fatal infection, has become treatable, but continues to be associated with increased mortality. Hepatitis B and C viral infections can lead to acute and chronic hepatitis, cirrhosis, or hepatocellular carcinoma. Young children and immunocompromised patients are more likely to develop chronic disease leading to increased morbidity and mortality, as compared to the healthy population. The hemodialysis population is at increased risk of blood-borne viral infections as compared to the general population due to multiple factors. Here we review risk factors of blood-borne viral infections, strategies for prevention, and approach to therapy in the pediatric hemodialysis population.

  View details for DOI 10.1007/s00467-018-4019-y

  View details for Web of Science ID 000468519900006

  View details for PubMedID 30032326

• Practical administration of intravenous contrast media in children: screening, prophylaxis, administration and treatment of adverse reactions PEDIATRIC RADIOLOGY Maloney, E., Iyer, R. S., Phillips, G. S., Menon, S., Lee, J. J., Callahan, M. J. 2019; 49 (4): 433-447

  Abstract

  Administration of intravenous contrast media to children is a routine practice at many clinical imaging centers, that can involve special considerations. In this paper, we provide practical information to facilitate optimal performance and oversight of this task. We provide targeted screening questions that can help to identify high-risk pediatric patients for both iodine-based and gadolinium-based intravenous contrast media administration. These include children at risk for allergic-like reactions, thyroid dysfunction, contrast-induced nephropathy, and nephrogenic systemic fibrosis. We make recommendations for addressing "yes" responses to screening questions using risk stratification schema that are specific to children. We also present criteria for selecting children for premedication prior to intravenous contrast administration, and suggest pediatric regimens. Additionally, we discuss practical nuances of intravenous contrast media administration to children and provide a quick-reference table of appropriate treatments with pediatric dosages for adverse contrast reactions.

  View details for DOI 10.1007/s00247-018-4306-6

  View details for Web of Science ID 000462754100002

  View details for PubMedID 30923875

  View details for PubMedCentralID 1584363

• Acute Kidney Injury in Nephrotic Syndrome FRONTIERS IN PEDIATRICS Menon, S. 2019; 6: 428

  Abstract

  Nephrotic syndrome (NS) is one of the commonest kidney diseases seen in childhood and is characterized by a relapsing remitting course. Various complications have been reported in children with NS, including infections, thromboembolism, hypovolemia, and acute kidney injury (AKI). There is often a modest decrease in renal function in patients with active proteinuria due to decreased glomerular permeability that improves when they go into remission. However, more pronounced AKI in NS is multifactorial in origin. It is most often secondary to hypovolemia, nephrotoxic medications, and infections, although other reasons may also be seen. Recent years have seen an increase in the incidence of AKI in NS. There is limited data on the correlation between AKI in pediatric NS and long-term outcomes. A better understanding of this increasingly common condition will help improve patient outcomes.

  View details for DOI 10.3389/fped.2018.00428

  View details for Web of Science ID 000455656900001

  View details for PubMedID 30693275

  View details for PubMedCentralID PMC6340287

• Urinary biomarker incorporation into the renal angina index early in intensive care unit admission optimizes acute kidney injury prediction in critically ill children: a prospective cohort study NEPHROLOGY DIALYSIS TRANSPLANTATION Menon, S., Goldstein, S. L., Mottes, T., Fei, L., Kaddourah, A., Terrell, T., Arnold, P., Bennett, M. R., Basu, R. K. 2016; 31 (4): 586-594

  Abstract

  The inconsistent ability of novel biomarkers to predict acute kidney injury (AKI) across heterogeneous patients and illnesses limits integration into routine practice. We previously retrospectively validated the ability of the renal angina index (RAI) to risk-stratify patients and provide context for confirmatory serum biomarker testing for the prediction of severe AKI.We conducted this first prospective study of renal angina to determine whether the RAI on the day of admission (Day0) risk-stratified critically ill children for 'persistent, severe AKI' on Day 3 (Day3-AKI: KDIGO Stage 2-3) and whether incorporation of urinary biomarkers in the RAI model optimized AKI prediction.A total of 184 consecutive patients (52.7% male) were included. Day0 renal angina was present (RAI ≥8) in 60 (32.6%) patients and was associated with longer duration of mechanical ventilation (P = 0.04), higher number of organ failure days (P = 0.003) and increased mortality (P < 0.001) than in patients with absence of renal angina. Day3-AKI was present in 15/156 (9.6%) patients; 12/15 (80%) fulfilled Day0 renal angina. Incorporation of urinary biomarkers into the RAI model increased the specificity and positive likelihood, and demonstrated net reclassification improvement (P < 0.001) for the prediction of Day3-AKI. Inclusion of urinary neutrophil gelatinase-associated lipocalin increased the area under the curve receiver-operating characteristic of RAI for Day3-AKI from 0.80 [95% confidence interval (CI): 0.58, 1.00] to 0.97 (95% CI: 0.93, 1.00).We have now prospectively validated the RAI as a functional risk stratification methodology in a heterogeneous group of critically ill patients, providing context to direct measurement of novel urinary biomarkers and improving the prediction of severe persistent AKI.

  View details for DOI 10.1093/ndt/gfv457

  View details for Web of Science ID 000374228000015

  View details for PubMedID 26908772

  View details for PubMedCentralID PMC6281075

• Improved outcomes with peritoneal dialysis catheter placement after cardiopulmonary bypass in infants JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Kwiatkowski, D. M., Menon, S., Krawczeski, C. D., Goldstein, S. L., Morales, D. L., Phillips, A., Manning, P. B., Eghtesady, P., Wang, Y., Nelson, D. P., Cooper, D. S. 2015; 149 (1): 230-236

  Abstract

  Acute kidney injury (AKI) is common in infants after cardiopulmonary bypass and is associated with poor outcomes. Peritoneal dialysis improves outcomes in adults with AKI after bypass, but pediatric data are limited. This retrospective case-matched study was conducted to determine if the practice of peritoneal dialysis catheter (PDC) placement during congenital heart surgery is associated with improved clinical outcomes in infants at high risk for AKI.Forty-two infants undergoing congenital heart surgery with planned PDC placement (PDC+) were age-matched to infants undergoing similar surgery without PDC placement (PDC-). Demographic, baseline and outcome data were compared. Our primary outcome was negative fluid balance on postoperative days 1 to 3. Secondary outcomes included time to negative fluid balance, time to extubation, frequency of electrolyte corrective medications, inotrope scores, and other clinical outcomes.Baseline data did not differ between groups. The PDC+ group had a higher percentage of negative fluid balance on postoperative days 1 and 2 (57% vs 33%, P = .04; 85% vs 61%, P = .01). The PDC+ group had shorter time to negative fluid balance (16 vs 32 hours, P < .0001), earlier extubation (80 vs 104 hours, P = .02), improved inotrope scores (P = .04), and fewer electrolyte imbalances requiring correction (P = .03). PDC-related complications were rare.PDC use is safe and associated with earlier negative fluid balance and improved clinical outcomes in infants at high risk for AKI. Routine PDC use should be considered for infants undergoing cardiopulmonary bypass. Further prospective studies are essential to prove causative effects of PDC placement in this population.

  View details for DOI 10.1016/j.jtcvs.2013.11.040

  View details for Web of Science ID 000350550100066

  View details for PubMedID 24503323

• Acute Kidney Injury Associated with High Nephrotoxic Medication Exposure Leads to Chronic Kidney Disease after 6 Months JOURNAL OF PEDIATRICS Menon, S., Kirkendall, E. S., Hovi Nguyen, Goldstein, S. L. 2014; 165 (3): 522-+

  Abstract

  To assess the development of chronic kidney disease (CKD) after high nephrotoxic medication exposure-associated acute kidney injury (NTMx-AKI) in hospitalized children.We performed a retrospective cohort study of children exposed to an aminoglycoside for ≥3 days or ≥3 nephrotoxic medications simultaneously for the development of CKD at 6 months. Follow-up data >6 months after acute kidney injury (AKI) were retrieved from electronic health records. Outcomes in children with NTMx-AKI were compared with patients of same age and primary service distribution who were exposed to nephrotoxic medications but did not develop AKI (controls).One hundred patients with NTMx-AKI were assessed (mean age of 9.3 ± 6.9 years). Commonly involved services were bone marrow transplantation/oncology (59%), liver transplantation (13%), and pulmonary (13%). Pre-AKI estimated glomerular filtration rate (eGFR) was 119 ± 14.5 mL/min/1.73 m(2) (range 90-150 mL/min/1.73 m(2)). Mean discharge eGFR was 105.1 ± 27.1 mL/min/1.73 m(2). At 6 months after NTMx-AKI, eGFR (n = 77) was 113.8 ± 30.6 mL/min/1.73 m(2). Sixteen (20.7%) had eGFR of 60-90, 2 (2.6%) had eGFR <60, and 9 (11.6%) had eGFR >150 mL/min/1.73 m(2) (hyperfiltration). Twenty-four (68.5%) of 35 patients who were assessed for proteinuria had a urine protein-to-creatinine ratio >0.3 mg/mg, and 29 (37.6%) had hypertension. Twenty-six (33.7%) patients had CKD (proteinuria or eGFR <60 mL/min/1.73 m(2)). An additional 28 (36.3%) were considered to be at risk for CKD with hypertension, eGFR between 60 and 90 mL/min/1.73 m(2), or eGFR >150 mL/min/1.73 m(2). CKD, hypertension, and proteinuria were more common in the AKI cohort than in controls.Six months after NTMx-AKI, 70% of patients had evidence of residual kidney damage (reduced eGFR, hyperfiltration, proteinuria, or hypertension). Few underwent a complete evaluation for CKD. With studies showing an association between AKI and CKD, we suggest systematic comprehensive follow-up in children after NTMx-AKI.

  View details for DOI 10.1016/j.jpeds.2014.04.058

  View details for Web of Science ID 000341437100024

  View details for PubMedID 24928698

• Membranous nephropathy in children: clinical presentation and therapeutic approach PEDIATRIC NEPHROLOGY Menon, S., Valentini, R. P. 2010; 25 (8): 1419-1428

  Abstract

  The approach to the pediatric patient with membranous nephropathy (MN) can be challenging to the practitioner. The clinical presentation of the child with this histologic entity usually involves some degree of proteinuria ranging from persistent, subnephrotic-ranged proteinuria to overt nephrotic syndrome. Patients often have accompanying microscopic hematuria and may have azotemia or mild hypertension. Children presenting with nephrotic syndrome are often steroid resistant; as such, their biopsy for steroid-resistant nephrotic syndrome results in the diagnosis of MN. The practitioner treating MN in the pediatric patient must weigh the risks of immunosuppressive therapy against the benefits. In general, the child with subnephrotic proteinuria and normal renal function can likely be treated conservatively with angiotensin blockade (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) without the need for immunosuppressive therapy. Those with nephrotic syndrome are usually treated with steroids initially and often followed by alkylating agents (cyclophosphamide or chlorambucil). Calcineurin inhibitors may also be useful, but the relapse rate after their discontinuation remains high. The absence of controlled studies in children with MN makes treatment recommendations difficult, but until they are available, using the patient's clinical presentation and risk of disease progression appears to be the most prudent approach.

  View details for DOI 10.1007/s00467-009-1324-5

  View details for Web of Science ID 000278951200005

  View details for PubMedID 19908069

  View details for PubMedCentralID PMC2887508

• Fibrillary glomerulonephritis and renal failure in a child with systemic lupus erythematosus PEDIATRIC NEPHROLOGY Menon, S., Zeng, X., Valentini, R. 2009; 24 (8): 1577-1581

  Abstract

  Fibrillary glomerulonephritis (FGN) is a rare immune-mediated glomerulopathy characterized by randomly arranged immunoglobulin (Ig) deposits on electron microscopy. Only seven pediatric cases have been reported, and the incidence in adults is about 1.5%. A 12-year-old boy presented with systemic lupus erythematosus (SLE) with World Health Organization Class IV lupus nephritis. A repeat biopsy carried out due to a poor response to standard immunosuppressive therapy and worsening renal functions revealed diffuse proliferative glomerulonephritis with fibrillary deposits. Despite aggressive immunosuppression with plasmapheresis and rituximab, the patient developed end stage renal disease. This is an atypical pediatric case characterized by SLE-associated FGN and a poor prognosis.

  View details for DOI 10.1007/s00467-009-1168-z

  View details for Web of Science ID 000267109300020

  View details for PubMedID 19308460

• Efficacy of zinc supplements in reducing relapses in steroid-sensitive nephrotic syndrome PEDIATRIC NEPHROLOGY Arun, S., Bhatnagar, S., Menon, S., Saini, S., Hari, P., Bagga, A. 2009; 24 (8): 1583-1586

  Abstract

  Relapses in steroid-sensitive nephrotic syndrome (SSNS) often follow infections of the respiratory or gastrointestinal tract. Based on data that zinc supplements reduce the risk of infections, we examined the efficacy of such supplements in reducing relapse rates in these patients. Eighty-one patients with SSNS (1-16 years old) were stratified into frequent (n = 52) and infrequent (n = 29) relapsers and randomized to receive 12-months of therapy with the recommended dietary allowance of zinc (10 mg/day) (n = 40) or placebo (n = 41). Patients with frequent relapses also received long-term, alternate-day prednisolone. Subjects receiving zinc showed a 20% lower frequency of relapses, with 44.7% of the patients having sustained remission compared to 27.5% in the placebo group (P > 0.05). Patients with frequent relapses receiving zinc showed a 28% reduction in relapse rates and a significantly higher likelihood of sustained remission (P = 0.02). Findings from this double blind, randomized study suggest that zinc supplementation results in trends towards remission and reduced relapses, especially in patients with frequent relapses. Prospective, adequately powered studies are required for confirmation of these findings.

  View details for DOI 10.1007/s00467-009-1170-5

  View details for Web of Science ID 000267109300021

  View details for PubMedID 19347367

• Effectiveness of a Multidisciplinary Clinic in Managing Children with Chronic Kidney Disease Menon, S., Valentini, R. P., Kapur, G., Layfield, S., Mattoo, T. K. AMER SOC NEPHROLOGY. 2009: 1170-1175

  Abstract

  Long-term outcome of patients with chronic kidney disease (CKD) correlates with adequacy of predialysis care. This is best provided in a multidisciplinary clinic that integrates the services of a nephrologist with other staff. There is limited data about such clinics in children. The Children's Hospital of Michigan established a Chronic Renal Insufficiency (CRI) clinic in 2002 to provide comprehensive care to children with CKD. These children receive care from a nephrologist, nurse clinician, transplant coordinator, dietician, social worker, and psychologist. The objective of the study was to compare outcome variables between patients from the CRI clinic and a general nephrology clinic.This was a retrospective chart review of 44 patients with CKD stages 2 to 4, who were managed in the general nephrology clinic (1996-2001, n = 20) or the CRI clinic (2002-2007, n = 24) for 1 yr before starting renal replacement therapy (RRT). Laboratory parameters, growth, and dialysis access type at time of RRT were compared between the two cohorts.At RRT, patients from the CRI clinic had better hemoglobin, lower parathyroid hormone and calcium phosphorus product than patients followed in the general nephrology clinic. More patients from the general nephrology clinic had an unplanned initiation of dialysis compared with patients from the CRI clinic (50% versus 10.5%, P < 0.05).This indicates that children followed in a multidisciplinary clinic have better outcome variables and are more likely to achieve K/DOQI targets at initiation of dialysis. They are better prepared for dialysis with electively planned catheter insertion or functioning arteriovenous grafts/fistulae.

  View details for DOI 10.2215/CJN.05791108

  View details for Web of Science ID 000267693400005

  View details for PubMedID 19478098

  View details for PubMedCentralID PMC2709513

• Vitamin D insufficiency and hyperparathyroidism in children with chronic kidney disease PEDIATRIC NEPHROLOGY Menon, S., Valentini, R. P., Hidalgo, G., Peschansky, L., Mattoo, T. K. 2008; 23 (10): 1831-1836

  Abstract

  Chronic kidney disease (CKD) is associated with altered calcium-phosphate homeostasis and hyperparathyroidism due to decreased activity of 1alpha-hydroxylase and impaired activation of 25-hydroxyvitamin D3 [25(OH)D3]. In some patients these problems start earlier because of vitamin D deficiency. A retrospective review of patients followed in the chronic renal insufficiency clinic at Children's Hospital of Michigan assessed the prevalence of vitamin D deficiency in CKD stages 2-4 and evaluated the effect of treatment with ergocalciferol on serum parathormone (PTH). Blood levels of 1,25 dihydroxyvitamin D3, 25(OH)D3, and parathormone (PTH) were examined in 57 children (40 boys; mean age 10.6 years). Of 57 subjects, 44 (77.2%) had 25(OH)D3 levels < or =30 ng/ml, with overall mean of 26.4 +/- 14.3 ng/ml. PTH for patients with 25(OH)D3 levels >30 ng/ml was 67.84 +/- 29.09 ng/ml and in the remaining patients was elevated, at 120.36 +/- 86.42 ng/ml (p = 0.05). Following ergocalciferol treatment (22), PTH decreased from 122.13 +/- 82.94 ng/ml to 80.14 +/- 59.24 ng/ml (p < 0.001) over a period of 3 months. We conclude that vitamin D deficiency is common in children with CKD stages 2-4 and is associated with hyperparathyroidism in the presence of normal 1,25 dihydroxyvitamin D3. Its occurrence before significant renal impairment is noteworthy. Early diagnosis and appropriate treatment is emphasized.

  View details for DOI 10.1007/s00467-008-0842-x

  View details for Web of Science ID 000258902600014

  View details for PubMedID 18575896

• Treatment with mycophenolate mofetil and prednisolone for steroid-dependent nephrotic syndrome PEDIATRIC NEPHROLOGY Afzal, K., Bagga, A., Menon, S., Hari, P., Jordan, S. C. 2007; 22 (12): 2059-2065

  Abstract

  The management of patients with steroid-dependent nephrotic syndrome (SDNS) refractory to treatment with long-term steroids, levamisole and cyclophosphamide is difficult. We report our experience on long-term treatment with mycophenolate mofetil (MMF) and alternate-day prednisolone in 42 patients with SDNS previously treated with levamisole (n = 35) and/or cyclophosphamide (n = 37). The mean age (range) at onset of nephrotic syndrome was 37 (13-92) months and at treatment with MMF 104.7 (32-187) months. MMF was administered at a mean daily dose of 26.5 (16.6-31.3) mg/kg for 14.3 (6-45) months. The mean 6-monthly relapse rates decreased from 3.0 episodes before therapy to 0.9 episodes in the first 6 months, 0.7 in next 6 months, and 0.3 in those treated longer than 12 months (P < 0.0001). While on therapy, 32 (76.2%) patients showed 50% or more reduction in relapse rates, and nine (21.4%) had sustained remission. The cumulative dose of prednisolone declined significantly from 0.6 mg/kg per day before to 0.3 mg/kg per day while receiving MMF. Prednisolone requirement was reduced by 50% or more in 16 patients and between 40% and 50% in eight patients. Treatment continuation beyond 12 months resulted in sustained steroid sparing and reduced need for alternative treatments while maintaining low relapse rates. No patients had diarrhea, hematological abnormalities, or impaired renal function. This data confirms the efficacy and safety of treatment with MMF and tapering doses of alternate-day prednisolone in patients with SDNS and supports its use for longer than 12 months.

  View details for DOI 10.1007/s00467-007-0617-9

  View details for Web of Science ID 000250755700009

  View details for PubMedID 17938973

• Nephrotic syndrome preceding psoriasis in children PEDIATRIC NEPHROLOGY Bagga, A., Menon, S., Hari, P., Mantan, M., Dinda, A. 2007; 22 (9): 1373-1376

  Abstract

  Nephrotic syndrome is considered to be a late complication of psoriasis, reported usually in adults and characterized by IgA nephropathy or focal segmental glomerulosclerosis. We report on four children in whom steroid-resistant nephrotic syndrome either preceded (n = 3), by 41-120 months, or occurred simultaneously (n = 1) with psoriasis; renal histology showed minimal change disease. Therapy with corticosteroids and cyclosporine resulted in remission of renal and cutaneous symptoms. Minimal change nephrotic syndrome and psoriasis might share similar mechanisms of pathogenesis involving cell-mediated immunity.

  View details for DOI 10.1007/s00467-007-0487-1

  View details for Web of Science ID 000247977300021

  View details for PubMedID 17457619

• Etiology of nephrocalcinosis in northern Indian children PEDIATRIC NEPHROLOGY Mantan, M., Bagga, A., Virdi, V., Menon, S., Hari, P. 2007; 22 (6): 829-833

  Abstract

  This retrospective survey examines the etiology of nephrocalcinosis (NC) in 40 patients (26 boys), over an 8-year period. The median age at onset of symptoms and presentation was 36 months and 72 months, respectively. Clinical features included marked failure to thrive (82.5%), polyuria (60%) and bony deformities (52.5%). The etiology of NC included distal renal tubular acidosis (RTA) in 50% patients and idiopathic hypercalciuria and hyperoxaluria in 7.5% each. Other causes were Bartter syndrome, primary hypomagnesemia with hypercalciuria, severe hypothyroidism and vitamin D excess. No cause for NC was found in 12.5% patients. Specific therapy, where possible, ameliorated the biochemical aberrations, although the extent of NC remained unchanged. At a median (range) follow up of 35 (14-240) months, glomerular filtration rate (GFR) had declined from 82.0 (42-114) ml/min per 1.73 m2 body surface area to 70.8 (21.3-126.5) ml/min per 1.73 m2 body surface area (P = 0.001). Our findings confirm that, even with limited diagnostic facilities, protocol-based evaluation permits determination of the etiology of NC in most patients.

  View details for DOI 10.1007/s00467-006-0425-7

  View details for Web of Science ID 000245852400010

  View details for PubMedID 17285294

• Beneficial effects of rituximab therapy for systemic lupus erythematosus INDIAN JOURNAL OF PEDIATRICS Menon, S., Hari, P., Bagga, A. 2007; 74 (1): 79-82

  Abstract

  We report an 11-yr-old girl with systemic lupus erythematosus (SLE) with recurrent flares of skin and systemic manifestations, which were poorly controlled with conventional therapy. Treatment with rituximab, a monoclonal antibody against CD20, was associated with remission of symptoms and a steroid sparing effect that persisted for more than 9 months. Therapy with rituximab appears promising in subjects with SLE.

  View details for DOI 10.1007/s12098-007-0033-y

  View details for Web of Science ID 000249443000012

  View details for PubMedID 17264461

• Approach to renal tubular disorders. Indian journal of pediatrics Bagga, A., Bajpai, A., Menon, S. 2005; 72 (9): 771-6

  Abstract

  The renal tubule plays an important role in fluid and electrolyte homeostasis. Renal tubular disorders may affect multiple ( e.g., Fanconi syndrome) or specific (e.g., nephrogenic diabetes insipidus, renal glucosuria) tubular functions. Most conditions are primary and monogenic but occasionally are secondary to other disorders (focal segmental glomerulosclerosis, cystinosis, Lowe syndrome). Tubular dysfunction should be considered in all children with failure to thrive, polyuria, refractory rickets, hypokalemia and metabolic acidosis. Careful clinical and laboratory evaluation is essential for appropriate diagnosis and specific management of these conditions.

  View details for DOI 10.1007/BF02734150

  View details for PubMedID 16186680