COVID-2019 Alert

The latest information about the 2019 Novel Coronavirus, including vaccine clinics for children ages 5 years old and older.

La información más reciente sobre el nuevo Coronavirus de 2019, incluidas las clínicas de vacunación para niños de 5 años en adelante.


Abanti Chaudhuri, MD

  • Abanti Chaudhuri



Work and Education

Professional Education

RG Kar Medical College & Hospital, Kolkata, W Bengal, India, 02/28/1994


Manchester University - St Mary's Hospital, Manchester, United Kingdom, 08/31/2003


Kaiser Permanente Oakland Pediatric Residency, Oakland, CA, 06/30/2007


Stanford University Pediatric Nephrology Fellowship, Stanford, CA, 06/30/2010

Board Certifications

Pediatric Nephrology, American Board of Pediatrics

Pediatrics, American Board of Pediatrics

All Publications

Update on COVID-19 vaccination in pediatric solid organ transplant recipients. Pediatric transplantation Dulek, D. E., Ardura, M. I., Green, M., Michaels, M. G., Chaudhuri, A., Vasquez, L., Danziger-Isakov, L., Posfay-Barbe, K. M., McCulloch, M. I., L'Huillier, A. G., Benden, C. 1800: e14235


BACKGROUND: COVID-19 vaccination has been successful in decreasing rates of SARS-CoV-2 infection in areas with high vaccine uptake. Cases of breakthrough SARS-CoV-2 infection remain infrequent among immunocompetent vaccine recipients who are protected from severe COVID-19. Robust data demonstrate the safety, immunogenicity, and effectiveness of several COVID-19 vaccine formulations. Importantly, Pfizer-BioNTech BNT162b2mRNA COVID-19 vaccine studies have now included children as young as 5years of age with safety, immunogenicity, and effectiveness data publicly available. In the United States, emergency use authorization by the Federal Drug Administration and approval from the Centers for Disease Control/Advisory Committee on Immunization Practices have been provided for the 5- to 11-year-old age group.METHODS: Members of the International Pediatric Transplant Association (IPTA) provide an updated review of current COVID-19 vaccine data with focus on pediatric solid organ transplant (SOT)-specific issues.RESULTS: This review provides an overview of current COVID-19 immunogenicity, safety, and efficacy data from key studies, with focus on data of importance to pediatric SOT recipients. Continued paucity of data in the setting of pediatric transplantation remains a challenge.CONCLUSIONS: Further studies of COVID-19 vaccination in pediatric SOT recipients are needed to better understand post-vaccine COVID-19T-cell and antibody kinetics and determine the optimal vaccine schedule. Increased COVID-19 vaccine acceptability, uptake, and worldwide availability are needed to limit the risk that COVID-19 poses to pediatric solid organ transplant recipients.

View details for DOI 10.1111/petr.14235

View details for PubMedID 35060251

Low dose rabbit antithymocyte globulin is non-inferior to higher dose in low-risk pediatric kidney transplant recipients. Pediatric nephrology (Berlin, Germany) Sigurjonsdottir, V. K., Maestretti, L., McGrath, A., Concepcion, W., Gallo, A., Jonsdottir, U., Grimm, P. C., Chaudhuri, A. 1800


BACKGROUND: Currently, there is no consensus among pediatric kidney transplant centers regarding the use and regimen for immunosuppressive induction therapy.METHODS: In this single center, retrospective cohort study, pediatric kidney transplant recipients transplanted between 1 May 2013 and 1 May 2018 with rabbit antithymocyte globulin (rATG) induction were included. We stratified patients based on immunological risk, with high risk defined as those with repeat transplant, preformed donor specific antibody, current panel-reactive antibodies>20%, 0 antigen match and/or African-American heritage. Outcome of interest was the incidence of biopsy proven acute rejection by 1year.RESULTS: A total of 166 patients met inclusion criteria. Age of patients was 12years (11 mo-21 y), (median, range), 21.5% received a living donor transplant and 50.6% were female. Low-immunologic-risk patients were divided into 2 groups, those who received the lower cumulative rATG dose of3.5mg/kg (n=52) versus the higher cumulative dose of>3.5mg/kg (n=47). The median total dose in the lower dose group was 3.1 (IQR 0.3) and 4.4 (IQR 0.8) in the higher dose group, P<0.001. Rejection rate did not differ significantly between the 2 treatment groups (7/52 vs. 6/47). None in the lower dose group developed BK nephropathy versus 3 in the higher dose group. Graft loss due to BK nephropathy occurred in 1 patient in the higher dose group. Graft loss in the whole cohort at 12months was a rare event (n=1) with 99.5% graft survival and 100% patient survival.CONCLUSIONS: Reduced rATG dosing (3.5mg/kg) when compared to higher dosing (>3.5mg/kg) is safe and effective in low-risk pediatric kidney transplant recipients without increasing risk of rejection. A higher resolution version of the Graphical abstract is available as Supplementary information.

View details for DOI 10.1007/s00467-021-05407-y

View details for PubMedID 35006359

Postoperative Acute Kidney Injury in Williams Syndrome Compared With Matched Controls. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies Yokota, R., Kwiatkowski, D. M., Journel, C., Adamson, G. T., Zucker, E., Suarez, G., Lechich, K. M., Chaudhuri, A., Collins, R. T. 2022


Cardiovascular manifestations occur in over 80% of Williams syndrome (WS) patients and are the leading cause of morbidity and mortality. One-third of patients require cardiovascular surgery. Renal artery stenosis (RAS) is common in WS. No studies have assessed postoperative cardiac surgery-related acute kidney injury (CS-AKI) in WS. Our objectives were to assess if WS patients have higher risk of CS-AKI postoperatively than matched controls and if RAS could contribute to CS-AKI.This was a retrospective study of all patients with WS who underwent cardiac surgery at our center from 2010 to 2020. The WS study cohort was compared with a group of controls matched for age, sex, weight, and surgical procedure.Patients underwent cardiac surgery and postoperative care at Lucile Packard Children's Hospital Stanford.There were 27 WS patients and 43 controls (31% vs 42% female; p = 0.36). Median age was 1.8 years (interquartile range [IQR], 0.7-3.8 yr) for WS and 1.7 years (IQR, 0.8-3.1 yr) for controls.None.Postoperative hemodynamics, vasopressor, total volume input, diuretic administration, and urine output were collected in the first 72 hours. Laboratory studies were collected at 8-hour intervals. Multivariable analysis identified predictors of CS-AKI.Controlled for renal perfusion pressure (RPP) and vasoactive inotrope score (VIS), compared with controls, the odds ratio (OR) of CS-AKI in WS was 4.2 (95% CI, 1.1-16; p = 0.034). Higher RPP at postoperative hours 9-16 was associated with decreased OR of CS-AKI (0.88 [0.8-0.96]; p = 0.004). Increased VIS at hour 6 was associated with an increased OR of CS-AKI (1.47 [1.14-1.9]; p = 0.003). Younger age was associated with an increased OR of CS-AKI (1.9 [1.13-3.17]; p = 0.015).The OR of CS-AKI is increased in pediatric patients with WS compared with controls. CS-AKI was associated with VIS at the sixth postoperative hour. Increases in RPP and mean arterial pressure were associated with decreased odds of CS-AKI.

View details for DOI 10.1097/PCC.0000000000002872

View details for PubMedID 34982759

Racial Disparities in Pediatric Kidney Transplantation under the New Kidney Allocation System in the United States. Clinical journal of the American Society of Nephrology : CJASN Krissberg, J., Kaufmann, M., Gupta, A., Bendavid, E., Stedman, M., Cheng, X., Tan, J., Grimm, P., Chaudhuri, A. 2021


Background and Objectives: In December 2014, the Kidney Allocation System (KAS) was implemented to improve equity in access to transplantation, but preliminary studies in children show mixed results. Thus, we aimed to assess how the 2014 KAS policy change affected racial/ethnic disparities in pediatric kidney transplantation access and related outcomes. Design, setting, participants, and measurements: A retrospective cohort study of children <18 years of age active on the kidney transplant list from 2008 to 2019 using the Scientific Registry of Transplant Recipients. Log-logistic accelerated failure time models were used to determine time from first activation on the transplant list and time on dialysis to deceased-donor transplant, each with KAS era or race/ethnicity as the exposure of interest. We used logistic regression to assess odds of delayed graft function. Log-rank tests assessed time to graft loss within racial/ethnic groups across KAS eras. Results: All children experienced longer wait times from activation to transplantation post-KAS. In univariable analysis, Black or Hispanic children or other children of color experienced longer times from activation to transplant compared to White children in the both eras; this finding was largely attenuated after multivariable analysis (time ratio 1.16, (95% CI 1.01-1.32); 1.13 (1.00-1.28); 1.17 (0.96-1.41) post-KAS, respectively). Multivariable analysis also showed that racial/ethnic disparities in time from dialysis initiation to transplantation in the pre-KAS era was mitigated in the post-KAS era. There were no disparities in odds of delayed graft function. Black or Hispanic children experienced longer times with a functioning graft in the post-KAS era. Conclusions: No racial/ethnic disparities from activation to deceased donor transplantation were seen before or after implementation of KAS in multivariable analysis, while time on dialysis to transplantation and odds of short-term graft loss improved in equity after KAS, without compromising disparities in delayed graft function.

View details for DOI 10.2215/CJN.06740521

View details for PubMedID 34670797

COVID-19 vaccination in pediatric solid organ transplant recipients-Current state and future directions. Pediatric transplantation L'Huillier, A. G., Ardura, M. I., Chaudhuri, A., Danziger-Isakov, L., Dulek, D., Green, M., Michaels, M. G., Posfay-Barbe, K. M., Vasquez, L., Benden, C. 2021: e14031


BACKGROUND: Population-level COVID-19 immunization will play a key role in slowing down the SARS-CoV-2 pandemic on a global scale and protect the most at-risk individuals. Thanks to a formidable universal effort, several SARS-CoV-2 vaccines have been marketed less than a year since the first documented COVID-19 case, with promising safety, efficacy, and immunogenicity results in adults. As children were not included in the initial trials, no vaccine is currently approved for individuals <16 years of age. Similarly, immunosuppressed individuals, such as solid organ transplant recipients, were excluded from initial vaccine trials, limiting the understanding of vaccine immunogenicity and safety in this at-risk population. Thus, data regarding COVID-19 vaccination in pediatric solid organ transplantation recipients are currently lacking.METHODS: Members of the International Pediatric Transplant Association review the current general status of COVID-19 vaccines focusing on pediatric-specific issues.RESULTS: This review provides an overview of COVID-19 vaccines in pediatric SOT recipients and highlights the current paucity of data in both pediatric and transplant settings in terms of safety, immunogenicity, and clinical efficacy.CONCLUSIONS: Vaccine trials including children and transplant recipients are underway and will be necessary to characterize COVID-19 vaccine safety, immunogenicity, and efficacy, which will determine potential future research directions.

View details for DOI 10.1111/petr.14031

View details for PubMedID 34076928

SARS-CoV-2 and pediatric solid organ transplantation: Current knowns and unknowns. Pediatric transplantation L'Huillier, A. G., Danziger-Isakov, L., Chaudhuri, A., Green, M., Michaels, M. G., M Posfay-Barbe, K., van der Linden, D., Verma, A., McCulloch, M., Ardura, M. I. 2021: e13986


The COVID-19 pandemic has proven to be a challenge in regard to the clinical presentation, prevention, diagnosis, and management of SARS-CoV-2 infection among children who are candidates for and recipients of SOT. By providing scenarios and frequently asked questions encountered in routine clinical practice, this document provides expert opinion and summarizes the available data regarding the prevention, diagnosis, and management of SARS-CoV-2 infection among pediatric SOT candidates and recipients and highlights ongoing knowledge gaps requiring further study. Currently available data are still lacking in the pediatric SOT population, but data have emerged in both the adult SOT and general pediatric population regarding the approach to COVID-19. The document provides expert opinion regarding prevention, diagnosis, and management of SARS-CoV-2 infection among pediatric SOT candidates and recipients.

View details for DOI 10.1111/petr.13986

View details for PubMedID 33689201

Consensus Treatment Plans for Severe Pediatric Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. Arthritis care & research Morishita, K. A., Wagner-Weiner, L., Yen, E. Y., Sivaraman, V., James, K. E., Gerstbacher, D., Szymanski, A. M., O'Neil, K. M., Cabral, D. A., CARRA ANCA-Associated Vasculitis Workgroup, Akamine, K., Alperin, R., Benseler, S., Bloom, J., Bracaglia, C., Chaudhuri, A., Cooper, J., Covert, L., Edens, C., Fuhlbrigge, R., Go, E., Haftel, H., Higgins, G., Inman, C., Jerath, R., Lapidus, S., Li, S., Mammen, C., Mehta, J., Modica, R., Moussa, T., Pereira, M., Semo-Oz, R., Shenoi, S., Stern, S., Stward, K., Sundel, R., Toth, M., Twilt, M., Van Mater, H., Wenderfer, S., Wu, E., Yalcindag, A. 2021


OBJECTIVE: There is no standardized approach to the treatment of pediatric antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (ped-AAV). Because of the rarity of ped-AAV, randomized trials have not been feasible. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed consensus treatment plans (CTPs) for severe ped-AAV to enable the future study of comparative effectiveness and safety.METHODS: A workgroup of CARRA members (rheumatologists and nephrologists) formed the AAV working group. This group performed a literature review on existing evidence-based treatments and guidelines for the management of AAV. They determined that the target population for CTP development was patients <18 years with new-onset granulomatosis with polyangiitis (GPA), microscopic polyangiitis, or renal-limited AAV (eosinophilic-GPA was excluded) with presentation confined to those with severe disease i.e. organ- or life-threatening. Face-to-face consensus conferences employed nominal group techniques to identify treatment strategies for remission-induction and remission-maintenance, data elements to be systematically collected, and outcomes to be measured over time.RESULTS: The ped-AAV workgroup developed two CTPs for each of the remission-induction and remission-maintenance of severe AAV. A corticosteroid-weaning regimen for induction and maintenance, a core dataset, and outcome measures were also defined. A random sample of CARRA membership voted acceptance of the CTPs for remission-induction and remission-maintenance with a 94% (75/80) and 98% (78/80) approval rate respectively.CONCLUSION: Consensus methodology established standardized CTPs for treating severe ped-AAV. These CTPs were in principle accepted by CARRA-wide membership for pragmatic comparative effectiveness evaluation in a long-term registry.

View details for DOI 10.1002/acr.24590

View details for PubMedID 33675161

COVID-19 in pediatric kidney transplantation: The Improving Renal Outcomes Collaborative. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Varnell, C. n., Harshman, L. A., Smith, L. n., Liu, C. n., Chen, S. n., Al-Akash, S. n., Barletta, G. M., Belsha, C. n., Brakeman, P. n., Chaudhuri, A. n., Fadakar, P. n., Garro, R. n., Gluck, C. n., Goebel, J. n., Kershaw, D. n., Matossian, D. n., Nailescu, C. n., Patel, H. P., Pruette, C. n., Ranabothu, S. n., Rodig, N. n., Smith, J. n., VanSickle, J. S., Weng, P. n., Danziger-Isakov, L. n., Hooper, D. K., Seifert, M. n. 2021


There are limited data on the impact of COVID-19 in children with a kidney transplant. We conducted a prospective cohort study through the Improving Renal Outcomes Collaborative (IROC) to collect clinical outcomes data about COVID-19 in pediatric kidney transplant patients. Twenty-two IROC centers that care for 2732 patients submitted testing and outcomes data for 281 patients tested for SARS-CoV-2 by PCR. Testing indications included symptoms and/or potential exposures to COVID-19 (N=134, 47.7%) and/or testing per hospital policy (N=154, 54.8%). Overall, 24 (8.5%) patients tested positive, of which 15 (63%) were symptomatic. Of the COVID-19 positive patients, 16 were managed as outpatients, 6 received non-ICU inpatient care and 2 were admitted to the ICU. There were no episodes of respiratory failure, allograft loss, or death associated with COVID-19. To estimate incidence, sub-analysis was performed for thirteen centers that care for 1686 patients that submitted all negative and positive COVID-19 results. Of the 229 tested patients at these 13 centers, 10 (5 asymptomatic) patients tested positive, yielding an overall incidence of 0.6% and an incidence among tested patients of 4.4%. Pediatric kidney transplant patients in the U.S. had a low estimated incidence of COVID-19 disease and excellent short-term outcomes.

View details for DOI 10.1111/ajt.16501

View details for PubMedID 33452854

Management and prevention of varicella and measles infections in pediatric solid organ transplant candidates and recipients: An IPTA survey of current practice. Pediatric transplantation Pittet, L. F., Danziger-Isakov, L., Allen, U. D., Ardura, M. I., Chaudhuri, A., Goddard, E., Hocker, B., Michaels, M. G., Van der Linden, D., Green, M., Posfay-Barbe, K. M. 2020: e13830


BACKGROUND: Varicella and measles infections can be life-threatening after solid organ transplantation (SOT) but may be preventable with live-attenuated vaccines (LAV).METHODS: This survey conducted in January 2019 among subscribers of the International Pediatric Transplantation Association listserv aimed to explore the current strategies to prevent and manage both infections in the pediatric SOT population, including recommending LAV after SOT.RESULTS: The answers given by 95 pediatric SOT healthcare workers show that these strategies are not yet optimal and call for further education. In particular, 59% of respondents are unnecessarily waiting for a SOT candidate to be >1year of age to start administrating LAV before SOT. Interestingly, most respondents are willing to administer LAV after SOT (57%), and a fifth (21%) are already doing so, off-label. The survey queried the precautions taken to improve safety evaluations after LAV, and identified knowledge gaps and practitioners' concerns.CONCLUSION: The results of this survey could be used as a starting point for education and promotion of the safe administration of LAV in carefully selected SOT recipients; in turn, this would increase available data that would contribute to the development of evidence-based guidelines by the transplant societies and ultimately prevent these infections after SOT.

View details for DOI 10.1111/petr.13830

View details for PubMedID 32964637

The Improving Renal Outcomes Collaborative: Blood Pressure Measurement in Transplant Recipients. Pediatrics Seifert, M. E., Dahale, D. S., Kamel, M., Winterberg, P. D., Barletta, G., Belsha, C. W., Chaudhuri, A., Flynn, J. T., Garro, R., George, R. P., Goebel, J. W., Kershaw, D. B., Matossian, D., Misurac, J., Nailescu, C., Nguyen, C. R., Pearl, M., Pollack, A., Pruette, C. S., Singer, P., VanSickle, J. S., Verghese, P., Warady, B. A., Warmin, A., Weng, P. L., Wickman, L., Wilson, A. C., Hooper, D. K., IMPROVING RENAL OUTCOMES COLLABORATIVE (IROC) 2020


BACKGROUND AND OBJECTIVES: Hypertension is highly prevalent in pediatric kidney transplant recipients and contributes to cardiovascular death and graft loss. Improper blood pressure (BP) measurement limits the ability to control hypertension in this population. Here, we report multicenter efforts from the Improving Renal Outcomes Collaborative (IROC) to standardize and improve appropriate BP measurement in transplant patients.METHODS: Seventeen centers participated in structured quality improvement activities facilitated by IROC, including formal training in quality improvement methods. The primary outcome measure was the proportion of transplant clinic visits with appropriate BP measurement according to published guidelines. Prospective data were analyzed over a 12-week pre-intervention period and a 20-week active intervention period for each center and then aggregated as of the program-specific start date. We used control charts to quantify improvements across IROC centers. We applied thematic analysis to identify patterns and common themes of successful interventions.RESULTS: We analyzed data from 5392 clinic visits. At baseline, BP was measured and documented appropriately at 11% of visits. Center-specific interventions for improving BP measurement included educating clinic staff, assigning specific team member roles, and creating BP tracking tools and alerts. Appropriate BP measurement improved throughout the 20-week active intervention period to 78% of visits.CONCLUSIONS: We standardized appropriate BP measurement across 17 pediatric transplant centers using the infrastructure of the IROC learning health system and substantially improved the rate of appropriate measurement over 20 weeks. Accurate BP assessment will allow further interventions to reduce complications of hypertension in pediatric kidney transplant recipients.

View details for DOI 10.1542/peds.2019-2833

View details for PubMedID 32518170

Ureterostomy as an alternative to ileal conduits in pediatric kidney transplantation. Clinical transplantation Brubaker, A. L., Wu, H., Lee, A., Vuong, P., Stoltz, D. J., Chaudhuri, A., James, G., Grimm, P. C., Concepcion, W., Gallo, A. E. 2020: e13777


INTRODUCTION: Urinary diversion in pediatric renal transplant candidates with bladders not amenable to primary reconstruction can be achieved by pre-transplant ileal conduit creation. We performed cutaneous ureterostomies to limit pre-transplant surgery, protect the peritoneum for dialysis, transplant patients sooner, and preserve ureter length for future surgical reconstruction.METHODS: We compared four pediatric transplant recipients with ureterostomies to four recipients with ileal conduits from 2009-2017.RESULTS: All patients with ileal conduits developed at least one urinary tract infection (UTI) within one year of transplant and three of four patients had recurrent UTIs within the first year. Two patients required ileal conduit revisions for redundant conduits and recurrent UTIs. Of the four ureterostomy patients, two patients had UTIs within one year of transplant. Two patients developed ureterostomy strictures requiring revision at the fascial level; one was associated with a UTI.CONCLUSION: In our small case series, ureterostomy allowed for a single operative intervention with preservation of ureter length for later reconstruction. Ureterostomy is safe and recurrent UTI may be lower in the ureterostomy group. Long-term evaluation of ureterostomy for urinary diversion in pediatric kidney transplant is warranted.

View details for DOI 10.1111/ctr.13777

View details for PubMedID 31904131

Peak blood pressure and prediction of posterior reversible encephalopathy syndrome in children. Pediatric nephrology (Berlin, Germany) Gall, E. n., Chaudhuri, A. n., South, A. M. 2020


Hypertension is a risk factor for posterior reversible encephalopathy syndrome (PRES), but the timing and severity of hypertension relative to PRES are unknown. The objective was to identify a clinically meaningful blood pressure (BP) threshold that predicts PRES development in high-risk children.We recorded peak systolic BP, diastolic BP, BP z-scores, and mean arterial pressure over the 14days preceding clinical concern for PRES in 35 subjects who developed PRES, compared to 14 controls who had normal brain magnetic resonance imaging and similar underlying disease, renal function, and medications. We used multivariable logistic regression models adjusted for fluid overload and obesity to estimate the association of peak BP with PRES. We used receiver operating characteristic curves to determine which peak BP thresholds best predicted PRES and calculated the corresponding sensitivity, specificity, and positive and negative predictive values.Peak systolic BP z-score was most strongly associated with PRES (OR 3.97, 95% CI 1.62-9.74), and peak systolic BP z-score 3.0 predicted PRES (area under the curve 0.95, 95% CI 0.88-1.0) with 91% sensitivity and 85% specificity, indicating 94% positive predictive value and 79% negative predictive value.We demonstrated that peak systolic BP z-score 3.0 in the preceding 14days predicted PRES development in cases compared with controls in children at high risk. Our study suggests that stage 2 hypertension, corresponding to a z-score 3.0, could help define hypertensive emergency in high-risk children and indicate when more aggressive treatment is warranted to prevent neurologic injury.

View details for DOI 10.1007/s00467-020-04577-5

View details for PubMedID 32385528

Diarrhea in the pediatric solid organ transplantation recipient: A multidisciplinary approach to diagnosis and management. Pediatric transplantation Chaudhuri, A. n., Goddard, E. A., Green, M. n., Ardura, M. I. 2020: e13886


Diarrhea in the pediatric solid organ transplantation (SOT) recipient is a frequent complaint that is associated with significant morbidity and impaired quality of life. There are limited published data regarding the specific epidemiology, diagnostic evaluation, and treatment of diarrhea after SOT in children. Pediatric SOT recipients have an increased risk of developing diarrhea because of a generalized immunosuppressed state, epidemiologic exposures, and polypharmacy. There is a need to standardize the diagnostic evaluation of diarrhea in children after SOT to facilitate an accurate diagnosis and timely treatment. Herein, we review the available published data and propose a systematic, stepwise approach to the evaluation of diarrhea in this high-risk population, focusing on timely diagnosis of both infectious and non-infectious causes, in order to provide focused management. Prospective studies are needed to better assess the true prevalence, risk factors for, etiologies, and complications of diarrhea in pediatric SOT patients that will guide optimal management. Development of effective vaccines and antiviral therapies for enteric viruses may also contribute to improved outcomes.

View details for DOI 10.1111/petr.13886

View details for PubMedID 33142366

Evaluation and management of elevated blood pressures in hospitalized children PEDIATRIC NEPHROLOGY Chaudhuri, A., Sutherland, S. M. 2019; 34 (10): 167181
De novo complement-activating donor-specific antibodies in pediatric renal transplant recipients are highly responsive to therapy Sigurjonsdottir, V., Zhang, B. M., Vina, M., Chaudhuri, A., Concepcion, W., Gallo, A., Grimm, P. WILEY. 2019
Standardizing blood pressure measurement across 17 pediatric transplant centers: The improving renal outcomes collaborative Seifert, M. E., Garro, R., George, R. P., Barletta, G., Belsha, C. W., Chaudhuri, A., Goebel, J. W., Kershaw, D. B., Matossian, D., Misurac, J., Nailescu, C., Nguyen, C. R., Pearl, M., Pollack, A., Pruette, C. S., Singer, P., Verghese, P., Warady, B. A., Dahale, D. S., Hooper, D. K. WILEY. 2019
Infections among pediatric transplant candidates: An approach to decision-making. Pediatric transplantation L'Huillier, A. G., Green, M. n., Danziger-Isakov, L. n., Chaudhuri, A. n., Hcker, B. n., Van der Linden, D. n., Goddard, L. n., Ardura, M. I., Stephens, D. n., Verma, A. n., Evans, H. M., McCulloch, M. n., Michaels, M. G., Posfay-Barbe, K. M., Allen, U. D. 2019: e13375


The presence of infections in the immediate pretransplant period poses challenges in decision-making. Delaying transplantation because of these infections may be required, but is associated with a risk to the potential recipient. The aim of this project was to develop a structured framework based on expert opinion to guide decision-making regarding the safety of transplantation for candidates with infection immediately before transplant, and to show how this framework can be applied to clinical scenarios.Categories were created as follows: Category A: no delay; Category B: brief delay (1week); Category C: intermediate delay (>1week); and Category D: more prolonged or indefinite delay. A survey containing 59 clinical scenarios was sent to members of the IPTA ID CARE committee. Answers were reviewed, and the level of agreement was characterized as follows: Level 1: 75% agreement; Level 2:51%-74% agreement; and Level 3: 50% agreement. 95% CIs were calculated for the mean overall agreement across 59 scenarios.Among the panel, the agreement level ranged from 33% to 92% with the mean overall agreement across the 59 scenarios being 61%. For 7/59 scenarios, the lower bound of 95% CI was greater than 50%, indicating a difference at the 5% level of significance between the observed proportion and the chance level of 0.5.The document provides expert opinion regarding the need to delay transplantation in the setting of different infections. The most important points in the decision to proceed to SOT included the urgency of transplantation and the severity of infection.

View details for DOI 10.1111/petr.13375

View details for PubMedID 30838753

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


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

View details for PubMedID 30171355

Superior Hypertension Management in Pediatric Kidney Transplant Patients After Native Nephrectomy. Transplantation Brubaker, A. L., Stoltz, D. J., Chaudhuri, A., Maestretti, L., Grimm, P. C., Concepcion, W., Gallo, A. E. 2018; 102 (7): 117278


BACKGROUND: Native nephrectomy in pediatric kidney transplant recipients is performed for multiple indications. Posttransplant hypertension requiring medical management is common, and the effect of native nephrectomy on posttransplant hypertension is poorly studied. Our aim is to evaluate the impact of native nephrectomy on posttransplant hypertension.METHODS: One hundred thirty-six consecutive pediatric kidney transplant recipients from 2007 to 2012 were studied at a single institution and divided into 2 groups: no nephrectomy and native nephrectomy (unilateral and bilateral nephrectomy). Antihypertensive medication use was evaluated before nephrectomy/transplant, at discharge from transplant and at 1, 3, and 5 years posttransplant.RESULTS: In a bivariate analysis, nephrectomy was associated with a significant reduction in the percentage of patients requiring antihypertensive medication at the time of discharge (27.3%) and 1 year posttransplant (10.7%) as compared with patients without nephrectomy (71.7%, and 50%, respectively, P < 0.05). This trend toward reduction in antihypertensive medication in the nephrectomy group as compared with the no nephrectomy group persisted at 3 (18.6% versus 43.2%) and 5 years (19.7% versus 37.5%) posttransplant. Multivariable logistic regression demonstrated that patients without native nephrectomy had higher odds of requiring antihypertensive medication at the time of discharge (3.3) and 1 year (5.2) as compared with patients who underwent native nephrectomy (P = 0.036 and P = 0.013, respectively).CONCLUSIONS: Native nephrectomy reduces the odds of needing antihypertensive medication after transplant. The impact of native nephrectomy is crucial to the comprehensive management of pediatric transplant recipients where medication compliance is challenging and lifelong hypertension is known to negatively impact cardiovascular health.

View details for PubMedID 29953422

DUET: A Phase 2 Study Evaluating the Efficacy and Safety of Sparsentan in Patients with FSGS. Journal of the American Society of Nephrology : JASN Trachtman, H. n., Nelson, P. n., Adler, S. n., Campbell, K. N., Chaudhuri, A. n., Derebail, V. K., Gambaro, G. n., Gesualdo, L. n., Gipson, D. S., Hogan, J. n., Lieberman, K. n., Marder, B. n., Meyers, K. E., Mustafa, E. n., Radhakrishnan, J. n., Srivastava, T. n., Stepanians, M. n., Tesar, V. n., Zhdanova, O. n., Komers, R. n. 2018


We evaluated and compared the effects of sparsentan, a dual endothelin type A (ETA) and angiotensin II type 1 receptor antagonist, with those of the angiotensin II type 1 receptor antagonist irbesartan in patients with primary FSGS.In this phase 2, randomized, double-blind, active-control Efficacy and Safety of Sparsentan (RE-021), a Dual Endothelin Receptor and Angiotensin Receptor Blocker, in Patients with Focal Segmental Glomerulosclerosis (FSGS): A Randomized, Double-blind, Active-Control, Dose-Escalation Study (DUET), patients aged 8-75 years with biopsy-proven FSGS, eGFR>30 ml/min per 1.73 m2, and urinary protein-to-creatinine ratio (UP/C) 1.0 g/g received sparsentan (200, 400, or 800 mg/d) or irbesartan (300 mg/d) for 8 weeks, followed by open-label sparsentan only. End points at week 8 were reduction from baseline in UP/C (primary) and proportion of patients achieving FSGS partial remission end point (FPRE) (UP/C: 1.5 g/g and >40% reduction [secondary]).Of 109 patients randomized, 96 received study drugs and had baseline and week 8 UP/C measurements. Sparsentan-treated patients had greater reductions in UP/C than irbesartan-treated patients did when all doses (45% versus 19%; P=0.006) or the 400 and 800 mg doses (47% versus 19%; P=0.01) were pooled for analysis. The FSGS partial remission end point was achieved in 28% of sparsentan-treated and 9% of irbesartan-treated patients (P=0.04). After 8 weeks of treatment, BP was reduced with sparsentan but not irbesartan, and eGFR was stable with both treatments. Overall, the incidence of adverse events was similar between groups. Hypotension and edema were more common among sparsentan-treated patients but did not result in study withdrawals.Patients with FSGS achieved significantly greater reductions in proteinuria after 8 weeks of sparsentan versus irbesartan. Sparsentan was safe and well tolerated.

View details for PubMedID 30361325

Persistent C4d and antibody-mediated rejection in pediatric renal transplant patients PEDIATRIC TRANSPLANTATION South, A. M., Maestretti, L., Kambham, N., Grimm, P. C., Chaudhuri, A. 2017; 21 (7)

View details for DOI 10.1111/petr.13035

View details for Web of Science ID 000412845900020

Superior Long-Term Hypertension Management in Pediatric Kidney Transplant Recipients with Bilateral Native Nephrectomies Stoltz, D., Brubaker, A., Chaudhuri, A., Grimm, P., Concepcion, W., Gallo, A. WILEY. 2017: 76263
Persistent C4d and antibody-mediated rejection in pediatric renal transplant patients. Pediatric transplantation South, A. M., Maestretti, L. n., Kambham, N. n., Grimm, P. C., Chaudhuri, A. n. 2017; 21 (7)


Pediatric renal transplant recipient survival continues to improve, but ABMR remains a significant contributor to graft loss. ABMR prognostic factors to guide treatment are lacking. C4d staining on biopsies, diagnostic of ABMR, is associated with graft failure. Persistent C4d+ on follow-up biopsies has unknown significance, but could be associated with worse outcomes. We evaluated a retrospective cohort of 17 pediatric renal transplant patients diagnosed with ABMR. Primary outcome at 12months was a composite of 50% reduction in eGFR, transplant glomerulopathy, or graft failure. Secondary outcome was the UPCR at 12months. We used logistic and linear regression modeling to determine whether persistent C4d+ on follow-up biopsy was associated with the outcomes. Forty-one percent reached the primary outcome at 12months. Persistent C4d+ on follow-up biopsy occurred in 41% and was not significantly associated with the primary outcome, but was significantly associated with the secondary outcome (estimate 0.22, 95% CI 0.19-0.25, P<.001), after controlling for confounding factors. Persistent C4d+ on follow-up biopsies was associated with a higher UPCR at 12months. Patients who remain C4d+ on follow-up biopsy may benefit from more aggressive or prolonged ABMR treatment.

View details for PubMedID 28833936

Cysteamine in renal transplantation: A report of two patients with nephropathic cystinosis and the successful re-initiation of cysteamine therapy during the immediate post-transplant period. Pediatric transplantation Berryhill, A., Bhamre, S., Chaudhuri, A., Concepcion, W., Grimm, P. C. 2016; 20 (1): 141-145


Nephropathic cystinosis is a rare disorder causing the accumulation of intracellular cystine crystals in tissues. The damage to the proximal tubules of the kidneys results in Fanconi syndrome, and patients with cystinosis experience the progression of chronic kidney disease, resulting in the need for kidney transplantation. Treatment of cystinosis with cysteamine has proven to be effective; however, it has many gastrointestinal side effects that are concerning for transplant specialists during the immediate post-transplant period. Transplant specialists routinely discontinue cysteamine therapy for up to six weeks to ensure proper immunosuppressant absorption. This practice is worrisome because it communicates the acceptability of lapses of cysteamine treatment to patients. It may be better to re-initiate cysteamine therapy shortly after transplantation while the patient is followed more closely by the transplant team. This report presents two pediatric patients with nephropathic cystinosis who successfully restarted cysteamine therapy in the immediate post-transplant period without issue in regard to immunosuppression absorption or gastrointestinal side effects. These cases challenge current practice of discontinuing cysteamine therapy during kidney transplantation, and immediate re-initiation of cysteamine therapy in cystinosis patients post-transplant should be considered.

View details for DOI 10.1111/petr.12617

View details for PubMedID 26477696

Small pediatric deceased donors for pediatric renal transplant recipients PEDIATRIC TRANSPLANTATION Chaudhuri, A., Grimm, P., Concepcion, W. 2016; 20 (1): 7-10

View details for DOI 10.1111/petr.12646

View details for Web of Science ID 000371420800002

View details for PubMedID 26916965

Pediatric deceased donor renal transplantation: An approach to decision making I. Pediatric kidney allocation in the USA: The old and the new PEDIATRIC TRANSPLANTATION Chaudhuri, A., Gallo, A., Grimm, P. 2015; 19 (7): 776-784


Renal transplantation is the treatment of choice for children with end-stage renal disease. More than 50% of children receive a deceased donor renal transplant. Marked disparity between the number of children on the renal transplant wait list and the supply has prompted numerous advances to increase supply as well as maximize the utility of donor organs. Allocation of deceased donor kidneys is based on several criteria. The organ allocation system policy is continually evaluated and changed incrementally to optimize allocation. We, in the United Sates, are in the process of transitioning into a new kidney allocation system to enhance post-transplant survival benefit, increase utilization of donated kidneys, and increase transplant access for biologically disadvantaged candidates. This review will provide a brief overview of the organ sharing system in the United States, compare the "old" and the "new" allocation system, and discuss the considerations for the pediatric nephrologist while accepting a deceased donor kidney for a particular pediatric patient.

View details for DOI 10.1111/petr.12569

View details for Web of Science ID 000362580100024

View details for PubMedID 26426316

Pediatric deceased donor renal transplantation: An approach to decision making II. Acceptability of a deceased donor kidney for a child, a snap decision at 3 AM PEDIATRIC TRANSPLANTATION Chaudhuri, A., Gallo, A., Grimm, P. 2015; 19 (7): 785-791


Allocation of deceased donor kidneys is based on several criteria; however, the final decision to accept or reject the offered kidney is made by the potential recipient's transplant team (surgeon/nephrologist). Several considerations including assessment of the donor quality, the HLA match between the donor and the recipient, several recipient factors, the geographical location of the recipient, and the organ all affect the decision of whether or not to finally accept the organ for a particular recipient. This decision needs to be made quickly, often on the spot. Maximizing the benefit from this scarce resource raises difficult ethical issues. The philosophies of equity and utility are often competing. This article will discuss the several considerations for the pediatric nephrologist while accepting a deceased donor kidney for a particular pediatric patient.

View details for DOI 10.1111/petr.12582

View details for Web of Science ID 000362580100025

View details for PubMedID 26426405

Whether or not to accept a deceased donor kidney offer for a pediatric patient PEDIATRIC NEPHROLOGY Chaudhuri, A., James, G., Grimm, P. 2015; 30 (9): 1529-1536


The expansion of the number of children on the deceased donor renal transplant waitlist has far outstripped the supply of organs in most countries, leading to numerous adjustments to increase supply and to maximize the utility of donor organs. The system for organ allocation varies by country based on local laws, priorities, and resources. Adjustments are made to optimize allocation, enhance post-transplant survival benefit, decrease unequal transplant access, and optimize utilization of donated kidneys. Allocation of deceased donor kidneys is based on several criteria; however, the final decision to accept or reject the offered kidney is made by the potential recipient's transplant team (surgeon/nephrologist). Several considerations including assessment of the donor quality, the human leukocyte antigen (HLA) match between the donor and the recipient, numerous recipient factors, the geographical location of the recipient, and the organ all affect the decision to accept the organ or not for a particular recipient. This decision must be made quickly, often on the spot. Maximizing the benefit from this scarce resource raises difficult ethical issues. The philosophies of equity and utility are often competing. In this manuscript, we highlight a representative case that helps to focus on important issues for the pediatric nephrologist to consider while making the decision to accept a deceased donor kidney offer for a particular pediatric patient.

View details for DOI 10.1007/s00467-015-3139-x

View details for Web of Science ID 000359745600019

View details for PubMedID 26130248

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


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

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

View details for PubMedID 25266709

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


We hypothesized that the percent change in resistance (%R) from bioimpedance analysis (BIA) measurements during hemodialysis (HD) can provide information on pediatric HD patients' hydration status.Whole-body single-frequency BIA measurements were obtained before HD, each hour on HD, and after HD during two HD sessions. Pre-and post-HD weights, blood pressures, Crit-Line measurements, and intradialytic symptoms were collected on the day of the BIA measurements.One hundred and thirty BIA measurements were obtained from 14 HD patients. The group was 43% girls, and the mean age was 13.24.4years. Percent change in resistance was 13.510.8% at the end of HD; %R correlated with percent body weight change (%BW) following HD (r=-0.83, P<0.01), as well as with percent blood volume change (%BV) (r=-0.79, P<0.01). The %R was similar between patients with and without hypertension immediately before HD and was greater in those with intradialytic symptoms (19.17.7%) than in those without (9.911.2%) (P=0.02). Patients with left ventricular hypertrophy (LVH) had lower %R (7.29.7%) than those without (19.57.7%) (P=0.03). Left ventricular mass index (LVMI) also correlated strongly with %R (r=-0.79, P=0.004) and %BW (r=0.82, P=0.002).Our study showed that %R strongly correlates with %BW and %BV and that %R also correlated with intradialytic symptoms and LVMI.

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

View details for Web of Science ID 000338700400017

Immune cell function assay does not identify biopsy-proven pediatric renal allograft rejection or infection. Pediatric transplantation Ryan, C. M., Chaudhuri, A., Concepcion, W., Grimm, P. C. 2014; 18 (5): 446-452


Management of pediatric renal transplant patients involves multifactorial monitoring modalities to ensure allograft survival and prevent opportunistic infection secondary to immunosuppression. An ICFA, which utilizes CD4 T-cell production of ATP to assess immune system status, has been used to monitor transplant recipients and predict susceptibility of patients to rejection or infection. However, the validity of this assay to reflect immune status remains unanswered. In a two-yr retrospective study that included 31 pediatric renal transplant recipients, 42 patient blood samples were analyzed for immune cell function levels, creatinine, WBC (white blood cell) count, immunosuppressive drug levels, and viremia, concurrent with renal biopsy. T-cell ATP production as assessed by ICFA levels did not correlate with allograft rejection or with the presence or absence of viremia. ICFA levels did not correlate with serum creatinine or immunosuppressive drug levels, but did correlate with WBC count. The ICFA is unreliable in its ability to reflect immune system status in pediatric renal transplantation. Further investigation is necessary to develop methods that will accurately predict susceptibility of pediatric renal transplant recipients to allograft rejection and infection.

View details for DOI 10.1111/petr.12295

View details for PubMedID 24930482

Use of eculizumab and plasma exchange in successful combined liver-kidney transplantation in a case of atypical HUS associated with complement factor H mutation. Pediatric nephrology Tran, H., Chaudhuri, A., Concepcion, W., Grimm, P. C. 2014; 29 (3): 477-480


Atypical hemolytic uremic syndrome (aHUS) evolves into end-stage renal failure in nearly half of affected patients and is associated with defective regulation of the alternative complement pathway. Patients with a complement factor H (CFH) mutation have a 30-100% risk of graft loss due to aHUS recurrence or graft thrombosis. Since CFH is produced predominantly by the liver, combined liver-kidney transplant is a curative treatment option. One major unexpected risk includes liver failure secondary to uncontrolled complement activation. We report a successful combined liver-kidney transplantation with perioperative plasma exchange and use of the humanized anti-C5 monoclonal antibody eculizumab.An 11-month-old female presented with oliguric renal failure after 3 weeks of flu-like symptoms in the absence of diarrhea. Following the identification of Escherichia coli 0157:H7 in her stool, she was discharged home on peritoneal dialysis with a diagnosis of Shiga toxin-associated HUS. Three months later, she developed severe anemia, thrombocytopenia, and neurological involvement. aHUS was diagnosed and confirmed, and genetic testing revealed a mutation in CFH SCR20. Once donor organs became available, she received preoperative plasma exchange followed by eculizumab infusion with intra-operative fresh frozen plasma prior to combined liver-kidney transplant. At 19 months post-transplant, she continues to have excellent allograft and liver function without signs of disease recurrence.Perioperative use of eculizumab in conjunction with plasma exchange during simultaneous liver-kidney transplant can be used to inhibit terminal complement activity, thereby optimizing successful transplantation by reducing the risk of graft thrombosis.

View details for DOI 10.1007/s00467-013-2630-5

View details for PubMedID 24221349

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


We hypothesized that the percent change in resistance (%R) from bioimpedance analysis (BIA) measurements during hemodialysis (HD) can provide information on pediatric HD patients' hydration status.Whole-body single-frequency BIA measurements were obtained before HD, each hour on HD, and after HD during two HD sessions. Pre-and post-HD weights, blood pressures, Crit-Line measurements, and intradialytic symptoms were collected on the day of the BIA measurements.One hundred and thirty BIA measurements were obtained from 14 HD patients. The group was 43% girls, and the mean age was 13.24.4years. Percent change in resistance was 13.510.8% at the end of HD; %R correlated with percent body weight change (%BW) following HD (r=-0.83, P<0.01), as well as with percent blood volume change (%BV) (r=-0.79, P<0.01). The %R was similar between patients with and without hypertension immediately before HD and was greater in those with intradialytic symptoms (19.17.7%) than in those without (9.911.2%) (P=0.02). Patients with left ventricular hypertrophy (LVH) had lower %R (7.29.7%) than those without (19.57.7%) (P=0.03). Left ventricular mass index (LVMI) also correlated strongly with %R (r=-0.79, P=0.004) and %BW (r=0.82, P=0.002).Our study showed that %R strongly correlates with %BW and %BV and that %R also correlated with intradialytic symptoms and LVMI.

View details for PubMedID 24570069

Pediatric ambulatory blood pressure monitoring: diagnosis of hypertension. Pediatric nephrology Chaudhuri, A. 2013; 28 (7): 995-999


Pediatric hypertension (HTN) is a growing concern and should be diagnosed and treated aggressively to reduce the global disease burden. Ambulatory blood pressure monitoring (ABPM) is a useful clinical tool providing a more accurate description of the patient's blood pressure (BP) than office BP measurements, and can be considered the "gold standard" in the evaluation of the pediatric patient with a concern for HTN. The American Heart Association have suggested criteria for diagnosing ambulatory HTN, and research continues into further clarification of how to best utilize the large volume of data obtained from an ABPM report. ABPM has some limitations; however, the advantages far outweigh these. Routine use of ABPM is recommended among clinicians to better evaluate and assess the severity of a child's HTN, and for proper management in order to prevent target organ damage and the resulting sequelae, thereby reducing the burden of cardiovascular risk in hypertensive children and adolescents.

View details for DOI 10.1007/s00467-013-2470-3

View details for PubMedID 23591679

The Clinical Impact of Humoral Immunity in Pediatric Renal Transplantation JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chaudhuri, A., Ozawa, M., Everly, M. J., Ettenger, R., Dharnidharka, V., Benfield, M., Mathias, R., Portale, A., McDonald, R., Harmon, W., Kershaw, D., Vehaskari, V. M., Kamil, E., Baluarte, H. J., Warady, B., Li, L., Sigdel, T. K., Hsieh, S., Dai, H., Naesens, M., Waskerwitz, J., Salvatierra, O., Terasaki, P. I., Sarwal, M. M. 2013; 24 (4): 655-664


The development of anti-donor humoral responses after transplantation associates with higher risks for acute rejection and 1-year graft survival in adults, but the influence of humoral immunity on transplant outcomes in children is not well understood. Here, we studied the evolution of humoral immunity in low-risk pediatric patients during the first 2 years after renal transplantation. Using data from 130 pediatric renal transplant patients randomized to steroid-free (SF) or steroid-based (SB) immunosuppression in the NIH-SNSO1 trial, we correlated the presence of serum anti-HLA antibodies to donor HLA antigens (donor-specific antibodies) and serum MHC class 1-related chain A (MICA) antibody with both clinical outcomes and histology identified on protocol biopsies at 0, 6, 12, and 24 months. We detected de novo antibodies after transplant in 24% (23% of SF group and 25% of SB group), most often after the first year. Overall, 22% developed anti-HLA antibodies, of which 6% were donor-specific antibodies, and 6% developed anti-MICA antibody. Presence of these antibodies de novo associated with significantly higher risks for acute rejection (P=0.02), chronic graft injury (P=0.02), and decline in graft function (P=0.02). In summary, antibodies to HLA and MICA antigens appear in approximately 25% of unsensitized pediatric patients, placing them at greater risk for acute and chronic rejection with accelerated loss of graft function. Avoiding steroids does not seem to modify this incidence. Whether serial assessments of these antibodies after transplant could guide individual tailoring of immunosuppression requires additional study.

View details for DOI 10.1681/ASN.2012070663

View details for Web of Science ID 000316921700017

View details for PubMedID 23449533

View details for PubMedCentralID PMC3609135

Conversion From Tacrolimus/Mycophenolic Acid to Tacrolimus/Leflunomide to Treat Cutaneous Warts in a Series of Four Pediatric Renal Allograft Recipients TRANSPLANTATION Lieuko Nguyen, L., McClellan, R. B., Chaudhuri, A., Alexander, S. R., Chen, S. F., Concepcion, W., Grimm, P. 2012; 94 (5): 450-455


The challenge of immunosuppression in pediatric renal transplantation is to balance preventing rejection while avoiding infectious complications. A dermatological complication of immunosuppression is viral warts, which cause significant disfigurement and increase the risk of skin malignancy.We present three pediatric and adolescent renal allograft recipients with multiple, recalcitrant verrucae vulgares lesions and one patient with molluscum contagiosum who were switched from mycophenolate mofetil to leflunomide. Teriflunomide metabolite levels were carefully maintained between 50,000 and 100,000 ng/mL to balance its immunosuppressive and antiviral properties. No adverse events requiring discontinuation of leflunomide were encountered.Switching from mycophenolate mofetil to leflunomide successfully cleared verrucae vulgares and molluscum lesions in all four renal transplant patients.The ability to minimize and even resolve warts can improve quality of life by reducing risk of skin malignancies and emotional distress in solid organ transplant patients. Leflunomide is a potential therapeutic option for posttransplantation patients with skin warts because it serves both as an adjunct to the immunosuppressive regimen and an antiviral agent.

View details for DOI 10.1097/TP.0b013e318264351e

View details for Web of Science ID 000308668000012

View details for PubMedID 22960763

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


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

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

View details for PubMedID 21672106

Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis NATURE MEDICINE Wei, C., El Hindi, S., Li, J., Fornoni, A., Goes, N., Sageshima, J., Maiguel, D., Karumanchi, S. A., Yap, H., Saleem, M., Zhang, Q., Nikolic, B., Chaudhuri, A., Daftarian, P., Salido, E., Torres, A., Salifu, M., Sarwal, M. M., Schaefer, F., Morath, C., Schwenger, V., Zeier, M., Gupta, V., Roth, D., Rastaldi, M. P., Burke, G., Ruiz, P., Reiser, J. 2011; 17 (8): 952-U70


Focal segmental glomerulosclerosis (FSGS) is a cause of proteinuric kidney disease, compromising both native and transplanted kidneys. Treatment is limited because of a complex pathogenesis, including unknown serum factors. Here we report that serum soluble urokinase receptor (suPAR) is elevated in two-thirds of subjects with primary FSGS, but not in people with other glomerular diseases. We further find that a higher concentration of suPAR before transplantation underlies an increased risk for recurrence of FSGS after transplantation. Using three mouse models, we explore the effects of suPAR on kidney function and morphology. We show that circulating suPAR activates podocyte (3) integrin in both native and grafted kidneys, causing foot process effacement, proteinuria and FSGS-like glomerulopathy. Our findings suggest that the renal disease only develops when suPAR sufficiently activates podocyte (3) integrin. Thus, the disease can be abrogated by lowering serum suPAR concentrations through plasmapheresis, or by interfering with the suPAR-(3) integrin interaction through antibodies and small molecules targeting either uPAR or (3) integrin. Our study identifies serum suPAR as a circulating factor that may cause FSGS.

View details for DOI 10.1038/nm.2411

View details for Web of Science ID 000293507400028

View details for PubMedID 21804539

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


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

View details for DOI 10.2215/CJN.07960910

View details for Web of Science ID 000289223600026

View details for PubMedID 21273374

View details for PubMedCentralID PMC3069381

Efficacy and Safety of Thymoglobulin Induction as an Alternative Approach for Steroid-Free Maintenance Immunosuppression in Pediatric Renal Transplantation TRANSPLANTATION Li, L., Chaudhuri, A., Chen, A., Zhao, X., Bezchinsky, M., Concepcion, W., Salvatierra, O., Sarwal, M. M. 2010; 90 (12): 1516-1520


Given the recent withdrawal of daclizumab (DAC), the safety and efficacy of thymoglobulin (TMG) was tested as an alternative induction agent for steroid-free (SF) immunosuppression in pediatric kidney transplant recipients.Thirteen pediatric renal transplant recipients meeting defined high-risk criteria at transplantation were offered TMG induction and SF immunosuppression with maintenance mycophenolate mofetil and tacrolimus between October 2008 and January 2010. Patients were closely monitored at baseline, 3, 6, 9, and 12 months posttransplant for protocol biopsy and clinical outcomes. Outcomes were compared with 13 consecutively transplanted low-risk patients receiving an established DAC-based SF protocol (Sarwal et al., WA, American Transplant Congress 2003).There was a significant trend for overall decrease in the absolute lymphocyte counts in TMG group (F=5.86, mixed model group effect P=0.02), predominately at 3 months compared with DAC group (0.70.6 vs. 2.11.0, P=0.0004); however, lymphocyte count was recovered and was back to reference range by 6 months in TMG. There was trend toward more subclinical cytomegalovirus (15% vs. 0%) and BK viremia (17% vs. 0%) in the TMG group, with no differences in the incidence of subclinical Epstein Barr virus viremia (23% vs. 31%) or clinical viral disease. Mean graft function was excellent, and with a minimum follow-up of 6 months, there were no episodes of acute rejection.TMG seems to be a safe alternative induction strategy in patients for SF immunosuppression in pediatric renal transplantation. Extended follow-up and greater enrollment are necessary to fully explore the impact of TMG dosing on viral replication posttransplantation.

View details for DOI 10.1097/TP.0b013e3181fc8937

View details for Web of Science ID 000285377100042

View details for PubMedID 20935596

Compartmental Localization and Clinical Relevance of MICA Antibodies After Renal Transplantation TRANSPLANTATION Li, L., Chen, A., Chaudhuri, A., Kambham, N., Sigdel, T., Chen, R., Sarwal, M. M. 2010; 89 (3): 312-319


Antibodies (Ab) responses to major and minor human leukocyte antigen loci may impact graft survival after organ transplantation.A ProtoArray platform was used to study 37 serum samples from 15 renal transplant patients with (n=10) and without (n=5) acute rejection (AR) and seven normal controls, and the clinical relevance of major histocompatibility complex class I chain-related gene-A (MICA)-Ab measurements were investigated. Biopsy immunohistochemistry was conducted for localization of the MICA antigen.De novo MICA-Ab were detected in 11 of the 15 transplant patients in this study, irrespective of interval acute graft rejection. Mean MICA-Ab signal intensity was higher in transplant patients with C4d+AR (121.4) versus C4d-AR (4.3), correlated with donor-specific Ab to human leukocyte antigens (r=0.66, P=0.0078), was not elevated in cellular rejections, and correlated with decline in graft function over the subsequent year (r=0.73, P=0.0022). Integrative genomics accurately predicted localization of the MICA antigen to the glomerulus in the normal kidney (Li et al. Proc Natl Acad Sci USA 2009; 106: 4148), because this was confirmed subsequently by immunohistochemistry.Integrative genomics analysis of ProtoArray data is a powerful tool to ascertain de novo antibody responses after renal transplantation and to accurately predict the anatomical location of the target renal antigens. This proof-of-concept study on MICA measurements by ProtoArray demonstrates that antibody responses modulated to MICA after transplantation in patients, irrespective of graft rejection, may be high at the time of humoral rejection and may not be elevated in cellular rejection. Understanding that MICA is preferentially localized to the glomerulus may explain both immunoregulatory and pathogenic roles for MICA after transplantation.

View details for DOI 10.1097/TP.0b013e3181bbbe4c

View details for Web of Science ID 000274589200009

View details for PubMedID 20145522

View details for PubMedCentralID PMC2820825

Extended daclizumab monotherapy for rejection-free survival in non-adherent adolescent recipients of renal allografts PEDIATRIC TRANSPLANTATION Chaudhuri, A., Salvatierra, O., Sarwal, M. M. 2009; 13 (7): 927-932


Acute rejection episodes are almost inevitable in the face of immunosuppression non-adherence and a known risk factor for developing chronic allograft nephropathy and accelerated graft loss. Daclizumab, a humanized monoclonal antibody directed against the alpha chain of the IL-2 receptor, is an important advance for induction therapy in renal transplant immunosuppression, reducing early acute graft rejection without affecting the tolerability of standard immunosuppression, for both steroid-based and steroid-free immunosuppressive protocols, in children and adults. In the absence of depot immunosuppression for maintenance therapy, we explored extended daclizumab therapy as temporary maintenance immunosuppression for acute rejection prophylaxis in two patients with recalcitrant immunosuppression non-adherence. Both patients had prior episodes of aggressive acute rejection associated with their non-adherence but achieved stable and rejection-free renal allograft function with daclizumab monotherapy in the presence of documented non-adherence thus providing an effective bridge for up to 12 months until immunosuppression adherence was re-established with ongoing psychosocial support. This report suggests that daclizumab monotherapy over an extended period of time during the period of non-adherence in the post transplant period could be a rescue modality to avoid immune activation and thereby prevent acute rejection in the face of erratic maintenance immunosuppression.

View details for DOI 10.1111/j.1399-3046.2008.01081.x

View details for Web of Science ID 000270666600024

View details for PubMedID 19017291

Subclinical cytomegalovirus and Epstein-Barr virus viremia are associated with adverse outcomes in pediatric renal transplantation PEDIATRIC TRANSPLANTATION Li, L., Chaudhuri, A., Weintraub, L. A., Hsieh, F., Shah, S., Alexander, S., Salvatierra, O., Sarwal, M. M. 2007; 11 (2): 187-195


Post-transplant clinical disease with cytomegalovirus (CMV) and Epstein-Barr virus (EBV) is a known risk factor for graft dysfunction and lymphoproliferation. We postulate that subclinical, asymptomatic viremia also adversely impacts outcomes, and may warrant re-assessment of current monitoring and antiviral prophylaxis protocols. A single-center study was conducted on 102 pediatric (51 steroid-free and 51 matched steroid-based historical controls). Quantitative viral loads were serially monitored and correlated with outcome measures. Overall, the incidence of CMV and EBV clinical disease was 5% (1% CMV and 4% EBV); however, the incidence of subclinical viremia was 44% (12.7% CMV, 38.2% EBV, 6.9% CMV + EBV). Risk factors for subclinical viremia were EBV naivety (p = 0.07), age less than five yr (p = 0.04), lack of prophylaxis (p = 0.01), and steroid usage (p = 0.0007). Subclinical viremia was associated with lower three-yr graft function (p = 0.03), increased risk of acute rejection (odds ratio 2.07; p = 0.025), hypertension (p = 0.04), and graft loss (p = 0.03). Subclinical asymptomatic CMV and EBV viremia is a risk factor for graft injury and loss. These findings support the need for aggressive, serial viral monitoring to better determine the appropriate length of post-transplant antiviral prophylaxis, and to determine the effect of immunosuppression protocols on the development of viremia.

View details for DOI 10.1111/j.1399-3046.2006.00641.x

View details for PubMedID 17300499

Option of pre-emptive nephrectomy and renal transplantation for Bartter's syndrome PEDIATRIC TRANSPLANTATION Chaudhuri, A., Salvatierra, O., Alexander, S. R., Sarwal, M. M. 2006; 10 (2): 266-270


Bartter's syndrome (BS) is an incurable genetic disease, with variable response to supportive therapy relating to fluid and electrolyte management. Poor control or therapy non-compliance may result in frequent life threatening episodes of dehydration, acidosis and hypokalemia, with resultant adverse effects on patient quality of life (QOL). We report, for the first time, pre-emptive bilateral native nephrectomies and successful renal transplantation, prior to the onset of ESRD, for severe, clinically brittle, neonatal BS, resulting in correction of metabolic abnormalities and excellent graft function. We propose that fragile BS should be considered as a possible indication for early native nephrectomies and pre-emptive renal transplantation, procedures that results in a 'cure' for the underlying disease and significant improvements in patient QOL.

View details for DOI 10.1111/j.1399-3046.2005.00435.x

View details for PubMedID 16573620