Aileen Xinqian Wang

All Publications

• A Survey of United States Transplant Center Donation After Circulatory Death Kidney Transplant Practices in the Modern Era TRANSPLANTATION PROCEEDINGS Alghannam, K., Howard, B., Loza, J., Goussous, N., Sageshima, J., Mineyev, N. M., Wang, A., Perez, R., Than, P. A. 2024; 56 (8): 1712-1720

  Abstract

  The mismatch between the number of patients awaiting kidney transplantation and the supply of donor organs has contributed to the increase in kidney transplantation from donors after circulatory death (DCD). Persistently long waiting times have led the transplant community to continue to explore the use of expanded- criteria DCD kidneys. In parallel, advances in organ preservation strategies have contributed to an overall increase in DCD organ transplantation and are altering the transplant landscape. Some of these techniques may improve kidney allograft outcomes and affect how DCD kidneys are used. We aimed to better understand practices in accepting DCD kidney offers in the modern era.Directors of 196 US kidney transplant centers were emailed a link to an online survey over a 5-week period.Forty-eight out of the 364 directors (13%) responded, with all United Network for Organ Sharing regions represented. Definitions of warm ischemia time (WIT) used in DCD kidney evaluation varied widely among the respondents. The maximum total WIT limit varied, with 19 (39.6%) <60-minute responses, followed by 16 (33%) <90-minute responses, and 10 (20.8%) <120-minute responses.Despite increasing DCD kidney transplantation volumes in the United States, there are no standardized procurement biopsy practices, organ procurement organization preoperative protocols, or consensus definition or limits of WIT. Agreement on terminology may facilitate rapid clinical communication, efficiency of organ allocation and utilization, recording of data, research, and improvements in policy.

  View details for DOI 10.1016/j.transproceed.2024.07.010

  View details for Web of Science ID 001318966600001

  View details for PubMedID 39198066

• Impact of Warm Ischemia Time on Donation After Circulatory Death Kidney Transplant Outcomes CLINICAL TRANSPLANTATION Alghannam, K., Fine, J., Howard, B., Loza, J., Goussous, N. M., Sageshima, J., Mineyev, N. M., Wang, A. X., Perez, R. V., Than, P. A. 2024; 38 (8): e15436

  Abstract

  Efforts to address the shortage of donor organs include increasing the use of renal allografts from donors after circulatory death (DCD). While warm ischemia time (WIT) is thought to be an important factor in DCD kidney evaluation, few studies have compared the relationship between WIT and DCD kidney outcomes, and WIT acceptance practices remain variable.We conducted a single-center retrospective review of all adult patients who underwent deceased donor kidney transplantation from 2000 to 2021. We evaluated the impact of varied functional warm ischemia time (fWIT) in controlled DCD donors by comparing donor and recipient characteristics and posttransplant outcomes between high fWIT (>60 min), low fWIT (≤60 min), and kidneys transplanted from donors after brain death (DBD).Two thousand eight hundred eleven patients were identified, 638 received low fWIT DCD, 93 received high fWIT DCD, and 2080 received DBD kidneys. There was no significant difference in 5-year graft survival between the DCD low fWIT, high fWIT, and DBD groups, with 84%, 83%, and 83% of grafts functioning, respectively. Five-year patient survival was 91% in the low fWIT group, 92% in the high fWIT group, and 90% in the DBD group. An increase in kidney donor risk index (KDRI) (HR 3.37, 95% CI = 2.1-5.7) and high CIT compared to low CIT (HR 2.12, 95% CI = 1.4-3.1) have higher hazard ratios for 1-year graft failure.Increased acceptance of kidneys from selected DCD donors with prolonged fWIT may present an opportunity to increase kidney utilization while preserving outcomes. Our group specifically prioritizes the use of kidneys from younger donors, with lower KDPI, and without acute kidney injury, or risk factors for underlying chronic kidney disease.

  View details for DOI 10.1111/ctr.15436

  View details for Web of Science ID 001293560100001

  View details for PubMedID 39158959

• Parathyroidectomy and Cinacalcet Use in Medicare-Insured Kidney Transplant Recipients. American journal of kidney diseases : the official journal of the National Kidney Foundation Wang, A. X., Liu, S., Montez-Rath, M. E., Chertow, G. M., Lenihan, C. R. 2022

  Abstract

  RATIONALE & OBJECTIVE: Post-transplant hyperparathyroidism is common and treatment practices are poorly characterized. The goal of this study was to examine the incidence, associations, and outcomes of post-transplant parathyroidectomy and calcimimetic use in a cohort of Medicare-insured US kidney transplant recipients.STUDY DESIGN: Retrospective observational cohort study.SETTING & PARTICIPANTS: We used the US Renal Data System to extract demographic, clinical, and prescription data from Medicare Parts A, B and D-insured patients who received their first kidney transplant between 2007 and 2013. We excluded patients with pre-transplant parathyroidectomy.PREDICTORS: Calendar year of transplantation and pre-transplant patient characteristics.OUTCOMES: 1) Incidence of and secular trends in parathyroidectomy and cinacalcet use in the 3 years following transplant, 2) 90-day outcomes following post-transplant parathyroidectomy and cinacalcet initiation.ANALYTICAL APPROACH: Temporal trends and pre-transplant correlates of parathyroidectomy and cinacalcet use were assessed using proportional hazards models and multivariable Poisson regression, respectively.RESULTS: 30,127 patients met the inclusion criteria. 10,707 used cinacalcet pre-transplant. 551 patients underwent post-transplant parathyroidectomy and 5413 patients filled ≥ 1 prescription for cinacalcet. The rate of post-transplant parathyroidectomy was stable over time. In contrast, cinacalcet use increased during the period studied. Long dialysis vintage and pre-transplant cinacalcet use were strongly associated with post-transplant parathyroidectomy and cinacalcet use. Roughly one in four patients were hospitalized within 90 days of post-transplant parathyroidectomy, with hypocalcemia-related diagnoses being the most common complication. Parathyroidectomy (versus cinacalcet initiation) was not associated with an increase in acute kidney injury.LIMITATIONS: We lacked access to laboratory data to help assess severity of secondary/tertiary hyperparathyroidism. The cohort was limited to Medicare beneficiaries.CONCLUSIONS: Almost one fifth of our study cohort was treated with parathyroidectomy and/or cinacalcet. Further studies are needed to establish the optimal treatment for post-transplant hyperparathyroidism.

  View details for DOI 10.1053/j.ajkd.2022.07.015

  View details for PubMedID 36162617

• Cellular and humoral immune response to SARS-CoV-2 vaccination and booster dose in immunosuppressed patients: An observational cohort study. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology Yang, L. M., Costales, C., Ramanathan, M., Bulterys, P. L., Murugesan, K., Schroers-Martin, J., Alizadeh, A. A., Boyd, S. D., Brown, J. M., Nadeau, K. C., Nadimpalli, S. S., Wang, A. X., Busque, S., Pinsky, B. A., Banaei, N. 2022; 153: 105217

  Abstract

  BACKGROUND: Humoral and cellular immune responses to SARS-CoV-2 vaccination among immunosuppressed patients remain poorly defined, as well as variables associated with poor response.METHODS: We performed a retrospective observational cohort study at a large Northern California healthcare system of infection-naive individuals fully vaccinated against SARS-CoV-2 (mRNA-1273, BNT162b2, or Ad26.COV2.S) with clinical SARS-CoV-2 interferon gamma release assay (IGRA) ordered between January through November 2021. Humoral and cellular immune responses were measured by anti-SARS-CoV-2 S1 IgG ELISA (anti-S1 IgG) and IGRA, respectively, following primary and/or booster vaccination.RESULTS: 496 immunosuppressed patients (54% female; median age 50 years) were included. 62% (261/419) of patients had positive anti-S1 IgG and 71% (277/389) had positive IGRA after primary vaccination, with 20% of patients having a positive IGRA only. Following booster, 69% (81/118) had positive anti-S1 IgG and 73% (91/124) had positive IGRA. Factors associated with low humoral response rates after primary vaccination included anti-CD20 monoclonal antibodies (P<0.001), sphingosine 1-phsophate (S1P) receptor modulators (P<0.001), mycophenolate (P=0.002), and B cell lymphoma (P=0.004); those associated with low cellular response rates included S1P receptor modulators (P<0.001) and mycophenolate (P<0.001). Of patients who had poor humoral response to primary vaccination, 35% (18/52) developed a significantly higher response after the booster. Only 5% (2/42) of patients developed a significantly higher cellular response to the booster dose compared to primary vaccination.CONCLUSIONS: Humoral and cellular response rates to primary and booster SARS-CoV-2 vaccination differ among immunosuppressed patient groups. Clinical testing of cellular immunity is important in monitoring vaccine response in vulnerable populations.

  View details for DOI 10.1016/j.jcv.2022.105217

  View details for PubMedID 35714462

• Long-term Apheresis in the Management of Patients With Recurrent Focal Segmental Glomerulosclerosis After Kidney Transplantation. Kidney international reports Uffing, A., Hullekes, F., Hesselink, D. A., Mansur, J. B., Malvezzi, P., de Vries, A. P., Seeger, H., Manfro, R. C., Nissaisorakarn, P., Wang, A. X., Reindl-Schwaighofer, R., Sanchez-Russo, L., Cravedi, P., Riella, L. V., Berger, S. P. 2022; 7 (6): 1424-1427

  View details for DOI 10.1016/j.ekir.2022.03.002

  View details for PubMedID 35685308

• Effect of nirmatrelvir/ritonavir on calcineurin inhibitor levels: Early experience in four SARS-CoV-2 infected kidney transplant recipients AMERICAN JOURNAL OF TRANSPLANTATION Wang, A. X., Koff, A., Hao, D., Tuznik, N. M., Huang, Y. 2022; 22 (8): 2117-2119

  View details for DOI 10.1111/ajt.16997

  View details for Web of Science ID 000759541200001

  View details for PubMedID 35158412

  View details for PubMedCentralID PMC9111225

• SARS-CoV-2 Neutralizing Monoclonal Antibodies for the Treatment of COVID-19 in Kidney Transplant Recipients. Kidney360 Wang, A. X., Busque, S., Kuo, J., Singh, U., Roeltgen, K., Pinsky, B. A., Chertow, G. M., Scandling, J. D., Lenihan, C. R. 2022; 3 (1): 133-143

  Abstract

  Background: Morbidity and mortality associated with coronavirus disease 2019 (COVID-19) infection in kidney transplant recipients are high and early outpatient interventions to prevent progression to severe disease are needed. SARS-CoV-2 neutralizing mAbs, including bamlanivimab and casirivimab-imdevimab, received emergency use authorization in the United States in November 2020 for treatment of mild to moderate COVID-19 disease.Methods: We performed a retrospective analysis of 27 kidney transplant recipients diagnosed with COVID-19 between July 2020 and February 2021 who were treated with bamlanivimab or casirivimab-imdevimab and immunosuppression reduction. We additionally identified 13 kidney transplant recipients with COVID-19 who had mild to moderate disease at presentation, who did not receive mAbs, and had SARS-CoV-2 serology testing available.Results: There were no deaths or graft failures in either group. Both infusions were well tolerated. Four of the 27 patients treated with mAbs required hospitalization due to COVID-19. Four of 13 patients who did not receive mAbs required hospitalization due to COVID-19. Patients who received mAbs demonstrated measurable anti-SARS-CoV-2 IgG with angiotensin-converting enzyme 2 (ACE2) receptor blocking activity at the highest level detectable at 90 days postinfusion, whereas ACE2 blocking activity acquired from natural immunity in the mAb-untreated group was weak.Conclusions: Bamlanivimab and casirivimab-imdevimab combined with immunosuppression reduction were well tolerated and associated with favorable clinical outcomes in kidney transplant recipients diagnosed with mild to moderate COVID-19.

  View details for DOI 10.34067/KID.0005732021

  View details for PubMedID 35368573

• Post-Transplant Nephrocalcinosis: A Single-Center Case Series Wang, A., Charu, V., Lenihan, C. R. AMER SOC NEPHROLOGY. 2021: 843

  View details for Web of Science ID 001265894204225

• Recurrence of IgA Nephropathy after Kidney Transplantation in Adults. Clinical journal of the American Society of Nephrology : CJASN Uffing, A., Perez-Saez, M. J., Jouve, T., Bugnazet, M., Malvezzi, P., Muhsin, S. A., Lafargue, M., Reindl-Schwaighofer, R., Morlock, A., Oberbauer, R., Buxeda, A., Burballa, C., Pascual, J., von Moos, S., Seeger, H., La Manna, G., Comai, G., Bini, C., Russo, L. S., Farouk, S., Nissaisorakarn, P., Patel, H., Agrawal, N., Mastroianni-Kirsztajn, G., Mansur, J., Tedesco-Silva, H., Ventura, C. G., Agena, F., David-Neto, E., Akalin, E., Alani, O., Mazzali, M., Manfro, R. C., Bauer, A. C., Wang, A. X., Cheng, X. S., Schold, J. D., Berger, S. P., Cravedi, P., Riella, L. V. 2021; 16 (8): 1247-1255

  Abstract

  BACKGROUND AND OBJECTIVES: In patients with kidney failure due to IgA nephropathy, IgA deposits can recur in a subsequent kidney transplant. The incidence, effect, and risk factors of IgA nephropathy recurrence is unclear, because most studies have been single center and sample sizes are relatively small.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a multicenter, international, retrospective study to determine the incidence, risk factors, and treatment response of recurrent IgA nephropathy after kidney transplantation. Data were collected from all consecutive patients with biopsy-proven IgA nephropathy transplanted between 2005 and 2015, across 16 "The Post-Transplant Glomerular Disease" study centers in Europe, North America, and South America.RESULTS: Out of 504 transplant recipients with IgA nephropathy, recurrent IgA deposits were identified by kidney biopsy in 82 patients; cumulative incidence of recurrence was 23% at 15 years (95% confidence interval, 14 to 34). Multivariable Cox regression revealed a higher risk for recurrence of IgA deposits in patients with a pre-emptive kidney transplant (hazard ratio, 3.45; 95% confidence interval, 1.31 to 9.17) and in patients with preformed donor-specific antibodies (hazard ratio, 2.59; 95% confidence interval, 1.09 to 6.19). After kidney transplantation, development of de novo donor-specific antibodies was associated with subsequent higher risk of recurrence of IgA nephropathy (hazard ratio, 6.65; 95% confidence interval, 3.33 to 13.27). Immunosuppressive regimen was not associated with recurrent IgA nephropathy in multivariable analysis, including steroid use. Graft loss was higher in patients with recurrence of IgA nephropathy compared with patients without (hazard ratio, 3.69; 95% confidence interval, 2.04 to 6.66), resulting in 32% (95% confidence interval, 50 to 82) graft loss at 8 years after diagnosis of recurrence.CONCLUSIONS: In our international cohort, cumulative risk of IgA nephropathy recurrence increased after transplant and was associated with a 3.7-fold greater risk of graft loss.

  View details for DOI 10.2215/CJN.00910121

  View details for PubMedID 34362788

• COVID-19 and Kidney Transplantation: Results from the TANGO International Transplant Consortium. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Cravedi, P. n., Suraj, S. M., Azzi, Y. n., Haverly, M. n., Farouk, S. n., Pérez-Sáez, M. J., Redondo-Pachón, M. D., Murphy, B. n., Florman, S. n., Cyrino, L. G., Grafals, M. n., Venkataraman, S. n., Cheng, X. S., Wang, A. X., Zaza, G. n., Ranghino, A. n., Furian, L. n., Manrique, J. n., Maggiore, U. n., Gandolfini, I. n., Agrawal, N. n., Patel, H. n., Akalin, E. n., Riella, L. V. 2020

  Abstract

  Kidney transplant recipients may be at high risk of developing critical COVID-19 illness due to chronic immunosuppression and comorbidities. We identified hospitalized adult kidney transplant recipients at 12 transplant centers in the US, Italy and Spain who tested positive for COVID-19. Clinical presentation, laboratory values, immunosuppression and treatment strategies were reviewed and predictors of poor clinical outcomes were determined through multivariable analyses. Among 9,845 kidney transplant recipients across centers, 144 were hospitalized due to COVID-19 during the 9-week study period. 65% were male with a mean age of 60 (±12) years, 40% Hispanic and 25% African-American. Prevalent comorbidities included hypertension (95%), diabetes (52%), obesity (49%), heart (28%) and lung (19%) disease. Therapeutic management included antimetabolite withdrawal (68%), calcineurin inhibitor withdrawal (23%), hydroxychloroquine (71%), antibiotics (74%), tocilizumab (13%) and antivirals (14%). During a median follow-up period of 52 days (IQR: 16-66 days), acute kidney injury occurred in 52% cases, respiratory failure requiring intubation in 29%, and mortality was 32%. The 44 patients who died were older, had lower lymphocyte counts and eGFR, higher serum lactate dehydrogenase, procalcitonin and IL-6 levels. In sum, hospitalized kidney transplant recipients with COVID-19 have higher rates of acute kidney injury and mortality.

  View details for DOI 10.1111/ajt.16185

  View details for PubMedID 32649791

• Simultaneous Coccidioidomycosis and Phaeohyphomycosis in a Kidney Transplant Recipient: A Case Report and Literature Review. Transplant infectious disease : an official journal of the Transplantation Society Puing, A. G., Couture-Cossette, A. n., Wang, A. X., Zygourakis, C. C., Cheng, X. n., Stevens, B. A., Banaei, N. n., Novoa, R. A., Ho, D. Y., Subramanian, A. n. 2020: e13365

  Abstract

  Advances in solid organ transplantation have improved the survival of end-stage organ disease at the expense of an increased risk for opportunistic infections. Unusual clinical presentations and the possibility of concurrent infections make diagnosing invasive fungal infection (IFI) more difficult. Here we present a case of simultaneous vertebral infection caused by Coccidioides immitis-posadasii and subcutaneous phaeohyphomycosis due to Nigrograna mackinnonii in a kidney transplant recipient. The diagnosis of both infections required invasive procedures to obtain tissue and a high index of suspicion that more than one IFI could be present. A multidisciplinary team approach for the management of immunocompromised patients with suspected or diagnosed IFI is warranted.

  View details for DOI 10.1111/tid.13365

  View details for PubMedID 32533741

• What Solid Organ Transplant Healthcare Providers should know about Renin-Angiotensin-Aldosterone System Inhibitors and COVID-19. Clinical transplantation Wong, S. Y., Brubaker, A. L., Wang, A. X., Taiwo, A. A., Melcher, M. L. 2020: e13991

  Abstract

  The data on the outcomes of solid organ transplant recipients who have contracted coronavirus disease 2019 (COVID-19) are still emerging. Kidney transplant recipients are commonly prescribed renin-angiotensin-aldosterone system (AAS) inhibitors given the prevalence of hypertension, diabetes, and cardiovascular disease. As the angiotensin-converting enzyme 2 (ACE2) facilitates the entry of coronaviruses into target cells, there have been hypotheses that preexisting use of Renin-Angiotensin-Aldosterone System (RAAS) inhibitors may increase the risk of developing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Given the common use of RAAS inhibitors among solid organ transplant recipients, we sought to review the RAAS cascade, the mechanism of SARS-CoV-2 entry, and pertinent data related to the effect of RAAS inhibitors on ACE2 to guide management of solid organ transplant recipients during the COVID-19 pandemic. At present there is no clear evidence to support the discontinuation of RAAS inhibitors in solid organ transplant recipients during the COVID-19 pandemic.

  View details for DOI 10.1111/ctr.13991

  View details for PubMedID 32446267

• Influence of Immunosuppression on Seroconversion Against SARS-Cov-2 in Two Kidney Transplant Recipients. Transplant infectious disease : an official journal of the Transplantation Society Wang, A. X., Quintero Cardona, O. n., Ho, D. Y., Busque, S. n., Lenihan, C. R. 2020: e13423

  Abstract

  Solid organ transplant recipients are at risk for infectious complications due to chronic immunosuppression. The outbreak of Coronavirus Disease 2019 (COVID-19) in United States has raised growing concerns for the transplant patient population. We seek to add to the current limited literature on COVID-19 in transplant recipients by describing the clinical course of two kidney transplant recipients with SARS-Cov-2 infection monitored by both RT-PCR and serology. Through careful adjustment of their immunosuppression regimen, both patients had excellent recovery with intact graft function and development of anti-SARS-Cov-2 antibodies.

  View details for DOI 10.1111/tid.13423

  View details for PubMedID 32701196

• Difficult Patient Behavior in Dialysis Facilities. Blood purification Janosevic, D., Wang, A. X., Wish, J. B. 2019; 47 (1-3): 254-258

  Abstract

  Difficult behavior exhibited by dialysis patients is a spectrum that includes nonadherence, verbal or physical abuse, and threatening acts. Such behaviors may lead to harmful consequences to the patient, other patients, the facility, and staff and can culminate in involuntary discharge. It is important to recognize that these "difficult behaviors" may be due to underlying psychosocial or medical issues, which places an onus on care providers to explore further. According to the Conditions for Coverage (CfC) for dialysis facilities, it falls upon the medical director to coordinate and oversee policies for patient satisfaction, patient safety and rights, involuntary discharges, and adverse events and outcomes. Thus, medical directors are liable for their own actions, and their staff for which they have oversight, for harm or perceived harm to patients in response to difficult behaviors. Guidelines to deal with specific patient behavior scenarios have been published by the Decreasing Dialysis Patient Conflict National Task Force of the Forum of end-stage renal disease (ESRD) Networks. The common denominator for these difficult scenarios is impaired communication, and the majority of patient concerns involve issues with staff, policies, treatments, and diet. Involuntary discharge of a patient should always be viewed as a last resort, and there is a structured process described in the CfC that requires the involvement of the respective ESRD Network and the facility medical director. As physicians, we are bound by ethical and growing legal obligations to act in an appropriate, ethical, and fair manner to patients who are considered to be "difficult."

  View details for DOI 10.1159/000494592

  View details for PubMedID 30522106

• Aldosterone deficiency prevents high-fat-feeding-induced hyperglycaemia and adipocyte dysfunction in mice. Diabetologia Luo, P., Dematteo, A., Wang, Z., Zhu, L., Wang, A., Kim, H. S., Pozzi, A., Stafford, J. M., Luther, J. M. 2013; 56 (4): 901-10

  Abstract

  Obesity is associated with aldosterone excess, hypertension and the metabolic syndrome, but the relative contribution of aldosterone to obesity-related complications is debated. We previously demonstrated that aldosterone impairs insulin secretion, and that genetic aldosterone deficiency increases glucose-stimulated insulin secretion in vivo. We hypothesised that elimination of endogenous aldosterone would prevent obesity-induced insulin resistance and hyperglycaemia.Wild-type and aldosterone synthase-deficient (As (-/-)) mice were fed a high-fat (HF) or normal chow diet for 12 weeks. We assessed insulin sensitivity and insulin secretion using clamp methodology and circulating plasma adipokines, and examined adipose tissue via histology.HF diet induced weight gain similarly in the two groups, but As (-/-) mice were protected from blood glucose elevation. HF diet impaired insulin sensitivity similarly in As (-/-) and wild-type mice, assessed by hyperinsulinaemic-euglycaemic clamps. Fasting and glucose-stimulated insulin were higher in HF-fed As (-/-) mice than in wild-type controls. Although there was no difference in insulin sensitivity during HF feeding in As (-/-) mice compared with wild-type controls, fat mass, adipocyte size and adiponectin increased, while adipose macrophage infiltration decreased. HF feeding significantly increased hepatic steatosis and triacylglycerol content in wild-type mice, which was attenuated in aldosterone-deficient mice.These studies demonstrate that obesity induces insulin resistance independently of aldosterone and adipose tissue inflammation, and suggest a novel role for aldosterone in promoting obesity-induced beta cell dysfunction, hepatic steatosis and adipose tissue inflammation.

  View details for DOI 10.1007/s00125-012-2814-8

  View details for PubMedID 23314847

  View details for PubMedCentralID PMC3593801