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Importance: Pediatric patients with complex medical problems benefit from pediatric sub-specialty care; however, a significant proportion of children live greater than 80 mi. away from pediatric sub-specialty care., Objective: To identify current knowledge gaps and outline concrete next steps to make progress on issues that have persistently challenged the pediatric nephrology workforce., Evidence Review: Workforce Summit 2.0 employed the round table format and methodology for consensus building using adapted Delphi principles. Content domains were identified via input from the ASPN Workforce Committee, the ASPN's 2023 Strategic Plan survey, the ASPN's Pediatric Nephrology Division Directors survey, and ongoing feedback from ASPN members. Working groups met prior to the Summit to conduct an organized literature review and establish key questions to be addressed. The Summit was held in-person in November 2023. During the Summit, work groups presented their preliminary findings, and the at-large group developed the key action statements and future directions., Findings: A holistic appraisal of the effort required to cover inpatient and outpatient sub-specialty care will help define faculty effort and time distribution. Most pediatric nephrologists practice in academic settings, so work beyond clinical care including education, research, advocacy, and administrative/service tasks may form a substantial amount of a faculty member's time and effort. An academic relative value unit (RVU) may assist in creating a more inclusive assessment of their contributions to their academic practice. Pediatric sub-specialties, such as nephrology, contribute to the clinical mission and care of their institutions beyond their direct billable RVUs. Advocacy throughout the field of pediatrics is necessary in order for reimbursement of pediatric sub-specialist care to accurately reflect the time and effort required to address complex care needs. Flexible, individualized training pathways may improve recruitment into sub-specialty fields such as nephrology., Conclusions and Relevance: The workforce crisis facing the pediatric nephrology field is echoed throughout many pediatric sub-specialties. Efforts to improve recruitment, retention, and reimbursement are necessary to improve the care delivered to pediatric patients., (© 2024. The Author(s).)

Neuroblastoma is a common pediatric tumor arising from the post-ganglionic sympathetic nervous system and is associated with hypertension in 25% of cases. We describe an unusual case of labile, multi-drug resistant hypertension associated with chemotherapy administration for neuroblastoma and provide potential management strategies in this scenario. We report the case of a 4-year-old female with a history of headaches who presented with hypertensive emergency and evidence of end-organ damage, including posterior reversible encephalopathy syndrome, acute cerebral infarct, concentric left ventricular hypertrophy, and growth failure secondary to a large, abdominal catecholamine-secreting neuroblastoma, which compressed the kidney vasculature and inferior vena cava. She was classified as intermediate risk according to Children's Oncology Group criteria and underwent chemotherapy, complicated by labile hypertension, followed by surgical resection. Vigilance in monitoring and treatment of hypertension is recommended during chemotherapy for neuroblastoma due to the potential catecholamine release in the setting of tumor lysis., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: Obesity is associated with increased complications, rejection, and graft loss after kidney transplantation in adult and pediatric recipients. Elevated body mass index (BMI) is a common contraindication to transplant at adult kidney transplant programs; however, there is no data on such limitations for pediatric patients., Methods: Between October and December 2022, we conducted a survey of Pediatric Nephrology Research Consortium centers assessing the use of BMI in pediatric kidney transplant evaluation. Centers reporting utilization of BMI cutoffs were invited to submit patient-level data on children declined for active transplant listing due to BMI., Results: Thirty-nine centers responded to the survey (42% response rate); 51% include BMI in their written listing criteria, with a median BMI "cutoff" of 39 kg/m 2 (range 30-50 kg/m 2 ). Between January 1, 2016, and December 31, 2021, 30 children at 15 transplant centers were declined for listing status due to BMI. Patient-level data was provided for 19 children (63%) who were denied active listing status; median BMI was 42 kg/m 2 (range 35.8-49.4 kg/m 2 ) and 84% were on dialysis. One year after evaluation, seven patients (37%) had proceeded to active wait list status. Eight (42%) remained in inactive status and four (21%) were unlisted; ten of these 12 patients (83%) were on dialysis., Conclusions: The use of BMI in pediatric kidney transplant evaluation and listing varies among centers, but BMI limits access to transplant for some children. More information is needed on the outcomes of obese pediatric kidney candidates who are and are not transplanted, to guide development of national and international consensus., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

We investigated the risks of post-acute and chronic adverse kidney outcomes of SARS-CoV-2 infection in the pediatric population via a retrospective cohort study using data from the RECOVER program. We included 1,864,637 children and adolescents under 21 from 19 children's hospitals and health institutions in the US with at least six months of follow-up time between March 2020 and May 2023. We divided the patients into three strata: patients with pre-existing chronic kidney disease (CKD), patients with acute kidney injury (AKI) during the acute phase (within 28 days) of SARS-CoV-2 infection, and patients without pre-existing CKD or AKI. We defined a set of adverse kidney outcomes for each stratum and examined the outcomes within the post-acute and chronic phases after SARS-CoV-2 infection. In each stratum, compared with the non-infected group, patients with COVID-19 had a higher risk of adverse kidney outcomes. For patients without pre-existing CKD, there were increased risks of CKD stage 2+ (HR 1.20; 95% CI: 1.13-1.28) and CKD stage 3+ (HR 1.35; 95% CI: 1.15-1.59) during the post-acute phase (28 days to 365 days) after SARS-CoV-2 infection. Within the post-acute phase of SARS-CoV-2 infection, children and adolescents with pre-existing CKD and those who experienced AKI were at increased risk of progression to a composite outcome defined by at least 50% decline in estimated glomerular filtration rate (eGFR), eGFR <15 mL/min/1.73m 2 , End Stage Kidney Disease diagnosis, dialysis, or transplant., Competing Interests: Dr. Jhaveri is a consultant for AstraZeneca, Seqirus, Dynavax, receives an editorial stipend from Elsevier and Pediatric Infectious Diseases Society and royalties from Up To Date/Wolters Kluwer. Dr. Ruby Patel is the Primary Investigator for FIONA study, no stipend or compensation being given. Dr. Modi reports research funding outside of this work from the National Institutes of Health, Centers for Disease Control, the Patient-Centered Outcomes Research Institute, Travere Therapeutics, and Boehringer Ingelheim. He is also the current director of the Kidney Research Network Data Coordinating Center. Dr. Harshman reports research funding outside of this work from the National Institutes of Health. Dr. Harshman reports research funding outside of this work from Bayer Pharmaceuticals. Dr. Verghese reports research funding outside of this work from the Department of Defense and Viracor Pharmaceuticals. Dr. Dixon reports consultancies with Novartis Pharmaceuticals, Alexion Astra Zeneca Rare Disease, Apellis Pharmaceuticals, and Arrowhead Pharmaceuticals.

Background: Adult kidney transplant recipients (KTRs) fully vaccinated against COVID-19 have substantial morbidity and mortality related to SARS-CoV-2 infection compared with the general population. However, little is known regarding the safety and efficacy of the COVID-19 vaccination series in pediatric KTRs., Methods: A multicenter, retrospective observational study was performed across nine pediatric transplantation centers. Eligible KTRs fully vaccinated against COVID-19 were enrolled and data were collected pertaining to SARS-CoV-2 infection incidence and severity, graft outcomes and post-vaccination safety profile, as well as overall patient survival., Results: A total of 247 patients were included in this investigation with a median age at transplantation of 11 years (IQR 5-15). SARS-CoV-2 infection was observed in 30/110 (27.27%) of fully vaccinated patients, tested post-transplant, within the defined follow-up period. Of these patients, 6/30 (18.18%) required hospitalization and 3/30 (12.12%) required reduction in immunosuppression, with no reported deaths. De novo donor-specific antibodies (DSAs) were found in 8/86 (9.30%) of DSA-tested patients with two experiencing rejection and subsequent graft loss. The overall incidence of rejection and graft loss among the total cohort was 11/247 (4.45%) and 6/247 (3.64%), respectively. A 100% patient survival was observed., Conclusions: Observationally, infectious outcomes of SARS-CoV-2 in fully vaccinated pediatric KTRs are excellent, with a low incidence of infection requiring hospitalization and no associated deaths. Though de novo DSAs were observed, there was minimal graft rejection and graft loss reported in the total cohort., (© 2024 Wiley Periodicals LLC.)

Background: Valganciclovir (valG), a cytomegalovirus (CMV) prophylactic agent, has dose-limiting side effects. The tolerability and effectiveness of valacyclovir (valA) as CMV prophylaxis is unknown., Methods: We conducted a randomized, open-label, single-center trial of valA versus valG for all posttransplant CMV prophylaxis in adult and pediatric kidney recipients. Participants were randomly assigned to receive valA or valG. Primary endpoints were the incidence of CMV viremia and side-effect related drug reduction with secondary assessment of incidence of EBV viremia., Results: Of the 137 sequential kidney transplant recipients enrolled, 26 % were positive and negative for CMV antibody in donor and recipient respectively. The incidence of CMV viremia (4 of 71 [6 %]; 8 of 67 [12 %] P = 0.23), time to viremia (P = 0.16) and area under CMV viral load time curve (P = 0.19) were not significantly different. ValG participants were significantly more likely to require side-effect related dose reduction (15/71 [21 %] versus 1/66 [2 %] P = 0.0003). Leukopenia was the most common reason for valG dose reduction and granulocyte-colony stimulating factor was utilized for leukopenia recovery more frequently (25 % in valG vs 5 % in valA: P = 0.0007). Incidence of EBV viremia was not significantly different., Conclusions: ValA has significantly less dose-limiting side effects than valG. In our study population, a significant increase in CMV viremia was not observed, in adults and children after kidney transplant, compared to valG., Trial Registration Number: NCT01329185., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Identification of abnormal blood pressure (BP) in children requires normative data. We sought to examine the feasibility of using "real-world" office BP data obtained from electronic health records (EHR) to generate age-, sex- and height-specific BP percentiles for children., Methods: Using data collected 01/01/2009-8/31/2021 from eight large children's healthcare organisations in PEDSnet, we applied a mixed-effects polynomial regression model with random slopes to generate Z-scores and BP percentiles and compared them with currently used normative BP distributions published in the 2017 American Academy of Paediatrics (AAP) Clinical Practise Guidelines (CPG)., Findings: We identified a study sample of 292,412 children (1,085,083 BP measurements), ages 3-17 years (53% female), with no chronic medical conditions, who were not overweight/obese and who were primarily seen for general paediatric care in outpatient settings. Approximately 45,000-75,000 children contributed data to each age category. The PEDSnet systolic BP percentile values were 1-4 mmHg higher than AAP CPG BP values across age-sex-height groups, with larger differences observed in younger children. Diastolic BP values were also higher in younger children; starting with age 7 years, diastolic BP percentile values were 1-3 mmHg lower than AAP CPG values. Cohen's Kappa was 0.90 for systolic BP, 0.66 for diastolic BP, and 0.80 overall indicating excellent agreement between PEDSnet and 2017 AAP CPG data for systolic BP and substantial agreement for diastolic BP., Interpretation: Our analysis indicates that real-word EHR data can be used to generate BP percentiles consistent with current clinical practise on BP management in children., Funding: Funding for this work was provided by the Preserving Kidney Function in Children with Chronic Kidney Disease (PRESERVE) study; Patient-Centred Outcomes Research Institute (PCORI) RD-2020C2020338 (Principal Investigator: Dr. Forrest; Co-Principal Investigator: Dr. Denburg)., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Rationale & Objective: PRESERVE seeks to provide new knowledge to inform shared decision-making regarding blood pressure (BP) management for pediatric chronic kidney disease (CKD). PRESERVE will compare the effectiveness of alternative strategies for monitoring and treating hypertension on preserving kidney function; expand the National Patient-Centered Clinical Research Network (PCORnet) common data model by adding pediatric- and kidney-specific variables and linking electronic health record data to other kidney disease databases; and assess the lived experiences of patients related to BP management., Study Design: Multicenter retrospective cohort study (clinical outcomes) and cross-sectional study (patient-reported outcomes [PROs])., Setting & Participants: PRESERVE will include approximately 20,000 children between January 2009-December 2022 with mild-moderate CKD from 15 health care institutions that participate in 6 PCORnet Clinical Research Networks (PEDSnet, STAR, GPC, PaTH, CAPRiCORN, and OneFlorida+). The inclusion criteria were ≥1 nephrologist visit and ≥2 estimated glomerular filtration rate (eGFR) values in the range of 30 to <90 mL/min/1.73 m 2 separated by ≥90 days without an intervening value ≥90 mL/min/1.73 m 2 and no prior dialysis or kidney transplant., Exposures: BP measurements (clinic-based and 24-hour ambulatory BP); urine protein; and antihypertensive treatment by therapeutic class., Outcomes: The primary outcome is a composite event of a 50% reduction in eGFR, eGFR of <15 mL/min/1.73 m 2 , long-term dialysis or kidney transplant. Secondary outcomes include change in eGFR, adverse events, and PROs., Analytical Approach: Longitudinal models for dichotomous (proportional hazards or accelerated failure time) and continuous (generalized linear mixed models) clinical outcomes; multivariable linear regression for PROs. We will evaluate heterogeneity of treatment effect by CKD etiology and degree of proteinuria and will examine variation in hypertension management and outcomes based on socio-demographics., Limitations: Causal inference limited by observational analyses., Conclusions: PRESERVE will leverage the PCORnet infrastructure to conduct large-scale observational studies that address BP management knowledge gaps for pediatric CKD, focusing on outcomes that are meaningful to patients., Plain-Language Summary: Hypertension is a major modifiable contributor to loss of kidney function in chronic kidney disease (CKD). The purpose of PRESERVE is to provide evidence to inform shared decision-making regarding blood pressure management for children with CKD. PRESERVE is a consortium of 16 health care institutions in PCORnet, the National Patient-Centered Clinical Research Network, and includes electronic health record data for >19,000 children with CKD. PRESERVE will (1) expand the PCORnet infrastructure for research in pediatric CKD by adding kidney-specific variables and linking electronic health record data to other kidney disease databases; (2) compare the effectiveness of alternative strategies for monitoring and treating hypertension on preserving kidney function; and (3) assess the lived experiences of patients and caregivers related to blood pressure management., (© 2023 Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc.)

Background: Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage kidney disease requiring kidney transplantation and can recur in the allograft in 30-80% of recipients resulting in reduced graft survival. Plasmapheresis has shown efficacy in treating some cases of recurrent FSGS but isolated plasmapheresis has not demonstrated efficacy in preventing recurrent FSGS. Rituximab has had anecdotal success in preventing recurrence in a single center study but has not been studied in combination with plasmapheresis for preventing FSGS recurrence., Methods: We are conducting a randomized, controlled, multicenter clinical trial of adult and pediatric kidney transplant recipients with primary FSGS to assess whether plasmapheresis in combination with rituximab prevents recurrent disease post-transplantation., Discussion: Rituximab combined with plasmapheresis is a promising, novel therapy to prevent recurrent FSGS, a disease with limited therapeutic options and no consensus guidelines for prevention or treatment., Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03763643, identifier NCT03763643., Competing Interests: Author MR is a site PI for unrelated clinical trials funded by Chinook, Kaneka, Travere, Reata, Sanofi and a consultant for Visterra. Author PV is a site PI for unrelated clinical trials funded by Akebia, Allosure, Otsuka, Pharmacosmos and Viracor and a consultant for NS Pharma. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rheault, Amaral, Bock, Chambers, Chavers, Ters, Garro, Gbadegesin, Govil, Harshman, Amer, Hooper, Israni, Riad, Sageshima, Shapiro, Seifert, Smith, Sung, Thomas, Wang and Verghese.)

Background: Acute kidney injury (AKI) is common in lupus nephritis (LN) and a risk factor for development of chronic kidney disease. In adults with LN, AKI severity correlates with the incidence of kidney failure and patient survival. Data on AKI outcomes in children with LN, particularly those requiring kidney replacement therapy (KRT), are limited., Methods: A multicenter, retrospective cohort study was performed in children diagnosed between 2010 and 2019 with LN and AKI stage 3 treated with dialysis (AKI stage 3D). Descriptive statistics were used to characterize demographics, clinical data, and kidney biopsy findings; treatment data for LN were not included. Logistic regression was used to examine the association of these variables with kidney failure., Results: Fifty-nine patients (mean age 14.3 years, 84.7% female) were identified. The most common KRT indications were fluid overload (86.4%) and elevated blood urea nitrogen/creatinine (74.6%). Mean follow-up duration was 3.9 ± 2.9 years. AKI recovery without progression to kidney failure occurred in 37.3% of patients. AKI recovery with later progression to kidney failure occurred in 25.4% of patients, and there was no kidney recovery from AKI in 35.6% of patients. Older age, severe (> 50%) tubular atrophy and interstitial fibrosis, and National Institutes of Health (NIH) chronicity index score > 4 on kidney biopsy were associated with kidney failure., Conclusions: Children with LN and AKI stage 3D have a high long-term risk of kidney failure. Severe tubular atrophy and interstitial fibrosis at the time of AKI, but not AKI duration, are predictive of kidney disease progression. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Lack of noninvasive diagnostic and prognostic biomarkers to reliably detect early allograft injury poses a major hindrance to long-term allograft survival in pediatric kidney transplant recipients., Methods: Validating Injury to the Renal Transplant Using Urinary Signatures Children's Study, a North American multicenter prospective cohort study of pediatric kidney transplant recipients, aims to validate urinary cell mRNA and metabolite profiles that were diagnostic and prognostic of acute cellular rejection (ACR) and BK virus nephropathy (BKVN) in adult kidney transplant recipients in Clinical Trials in Organ Transplantation-4. Specifically, we are investigating: (1) whether a urinary cell mRNA 3-gene signature ( 18S -normalized CD3ε, CXCL10 mRNA, and 18S ribosomal RNA) discriminates biopsies with versus without ACR, (2) whether a combined metabolite profile with the 3-gene signature increases sensitivity and specificity of diagnosis and prognostication of ACR, and (3) whether BKV-VP1 mRNA levels in urinary cells are diagnostic of BKVN and prognostic for allograft failure., Results: To date, 204 subjects are enrolled, with 1405 urine samples, including 144 biopsy-associated samples. Among 424 urine samples processed for mRNA, the median A260:280 ratio (RNA purity) was 1.91, comparable with Clinical Trials in Organ Transplantation-4 (median 1.82). The quality control failure rate was 10%. Preliminary results from urine supernatant showed that our metabolomics platform successfully captured a broad array of metabolites. Clustering of pool samples and overlay of samples from various batches demonstrated platform robustness. No study site effect was noted., Conclusions: Multicenter efforts to ascertain urinary biomarkers in pediatric kidney transplant recipients are feasible with high-quality control. Further study will inform whether these signatures are discriminatory and predictive for rejection and infection., Competing Interests: M.Snyder is a cofounder and on the advisory board of Personalis, SensOmics, January, Filtricine, Qbio, Protos, and Mirive. M.Snyder is also on the advisory board of Genapsys and Tailai. J.K. is a one-time Pediatric Advisory Board attendee for Reata Pharmaceuticals, Inc. The other authors declare no conflicts of interest., (Copyright © 2021 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Introduction: There are no guidelines regarding management of failed pediatric renal transplants., Materials & Methods: We performed a first of its kind multicenter study assessing prevalence of transplant nephrectomy, patient characteristics, and outcomes in pediatric renal transplant recipients with graft failure from January 1, 2006, to December 31, 2016., Results: Fourteen centers contributed data on 186 pediatric recipients with failed transplants. The 76 recipients that underwent transplant nephrectomy were not significantly different from the 110 without nephrectomy in donor or recipient demographics. Fifty-three percent of graft nephrectomies were within a year of transplant. Graft tenderness prompted transplant nephrectomy in 91% (P < .001). Patients that underwent nephrectomy were more likely to have a prior diagnosis of rejection within 3 months (43% vs 29%; P = .04). Nephrectomy of allografts did not affect time to re-listing, donor source at re-transplant but significantly decreased time to (P = .009) and incidence (P = .0002) of complete cessation of immunosuppression post-graft failure. Following transplant nephrectomy, recipients were significantly more likely to have rejection after re-transplant (18% vs 7%; P = .03) and multiple rejections in first year after re-transplant (7% vs 1%; P = .03)., Conclusions: Practices pertaining to failed renal allografts are inconsistent-40% of failed pediatric renal allografts underwent nephrectomy. Graft tenderness frequently prompted transplant nephrectomy. There is no apparent benefit to graft nephrectomy related to sensitization; but timing / frequency of immunosuppression withdrawal is significantly different with slightly increased risk for rejection following re-transplant., (© 2021 Wiley Periodicals LLC.)

Background: No consensus exists on the optimal timing for native nephrectomy in pediatric kidney transplant recipients. Data comparing outcomes between recipients undergoing pretransplant nephrectomy (staged nephrectomy with subsequent transplant) and those undergoing nephrectomy simultaneously with the transplant are lacking., Method: We studied 32 pediatric kidney transplant recipients who underwent native nephrectomy at a single center from 01/01/2011 to 12/31/2016. We divided recipients into two groups based on the nephrectomy timing (simultaneous nephrectomy/transplant and staged nephrectomy). We used Wilcoxon rank-sum test, Fisher's exact test, and Kaplan-Meier methods to compare outcomes., Results: Of 32 recipients, 20 underwent simultaneous and 12 underwent staged nephrectomy. Simultaneous recipients were younger (median (years): 2.0 vs 7.0; P = .049). Staged recipients were more likely to have proteinuria/hypoalbuminemia, whereas simultaneous recipients were more likely to have hydronephrosis/vesicoureteral reflux/urinary infections as nephrectomy indications (P = .06). Median prenephrectomy albumin for patients with nephrotic syndrome was significantly lower in staged recipients (median g/dL: 1.9 vs 3.8; P = .02). Total number of hospital days (including both procedures) was higher for staged recipients compared with simultaneous (one procedure) recipients (median (days): 17.0 vs 11.5; P = .05). We observed no difference in 5-year graft survival between the groups (95.0% vs 91.7%, P = .73). Patient survival was 100% in both groups over a median follow-up of 44.2 months. Surgical complications were similar between the groups., Conclusion: Staged and simultaneous native nephrectomy in pediatric kidney transplant recipients are associated with comparable outcomes., (© 2020 Wiley Periodicals LLC.)

Dapsone has been utilized for the prevention of Pneumocystis jirovecii pneumonia in immunosuppressed patients including pediatric kidney transplant recipients, in whom trimethoprim-sulfamethoxazole (TMP-SMX) is contraindicated. Dapsone adverse effects include methemoglobinemia, but there are no reports of the burden and impact of methemoglobinemia in pediatric kidney recipients that are taking dapsone for PJP prophylaxis. We conducted a retrospective chart review of all pediatric kidney recipients who had received dapsone at any time posttransplant. The indication, duration, and adverse effects of dapsone therapy were assessed. In addition, methemoglobin levels were assessed, and summary statistics performed. Data demonstrated that more than half of the patients on dapsone were not screened for methemoglobinemia. Of those screened, there was a significantly higher acquired-methemoglobinemia (77%) than previously reported in the literature. We also demonstrate significantly more anemia in patients on dapsone. Methemoglobinemia did not affect patient or graft survival and resolved with cessation of dapsone. We conclude that pediatric kidney recipients often develop methemoglobinemia and / or anemia on dapsone. We recommend if pediatric transplant recipients are prescribed dapsone, routine testing for methemoglobinemia and anemia should be done., (© 2020 Wiley Periodicals LLC.)

Background: Little data exist on re-hospitalization rates in pediatric kidney recipients (KTx) particularly with the evolution of transplant immunosuppression., Methods: In a single-center, retrospective study of pediatric KTx between 2006 and 2016, we assessed re-hospitalization after KTx admission, stratified by whether the re-admit was early (<30 days post-KTx discharge) or late (>30 days), and compared two different immunosuppression eras (one with and one without steroids)., Results: Of 197 KTx, 156 (79%) patients were re-hospitalized in 1st year, 85 (56%) within 30 days of discharge (total 490 1st year re-hospitalizations). Younger age was associated with early and late re-hospitalizations. African American race was associated with early re-hospitalizations. Of the 123 and 74 discharged on steroid-avoidance (maintenance immunosuppression included MMF in 95%; FK in 50%; CSA in 50%) and steroid-inclusive (AZA in 66%; MMF in 34%; FK in 30%; CSA in 70%), re-hospitalization rates, timing post-transplant, length, and number were not significantly different (P .38; .1; .56; .11). Admission diagnoses analysis demonstrated that steroid-avoidance recipients had anemia/leucopenia/thrombocytopenia, significantly more often, as one of their admission diagnoses (16% vs 4%; P < .001) and had a rejection diagnosis significantly less often (6% vs 18%; P < .001). Infection diagnoses were not statistically different between groups. Re-hospitalization, early or late, did not predict worse graft/ patient survival but predicted further hospitalizations., Conclusions: Re-hospitalization is common after pediatric transplant discharge and predicts further hospitalization regardless of discharge on or off steroids., (© 2020 Wiley Periodicals LLC.)

Background: Kidney transplant (KT) recipients have higher incidence of malignancies, including Human Papillomavirus (HPV)-associated cancers. Thus, HPV vaccines may have an important role in preventing HPV-related disease in this population; however, immunogenicity and safety data are lacking. Objective: To examine the immunological response and tolerability to HPV vaccination in pediatric KT recipients compared to future KT candidates. Methods: The quadrivalent HPV vaccine was administered to girls and boys age 9-18 recruited from seven centers part of the Pediatric Nephrology Research Consortium. Subjects were recruited for three groups: (1) CKD: chronic kidney disease stages 3, 4, and 5 not on dialysis; (2) Dialysis; (3) KT recipients. The outcome consisted of antibody concentrations against HPV 6, 11, 16, and 18. Geometric mean titers (GMTs) and seroconversion rates were compared. Vaccine tolerability was assessed. Results: Sixty-five participants were recruited: 18 in the CKD, 18 in the dialysis, and 29 into the KT groups. KT patients had significantly lower GMTs after vaccination for all serotypes. The percentages of subjects who reached seroconversion were overall lower for the KT group, reaching statistical significance for HPV 6, 11, and 18. Comparing immunosuppressed subjects (anyone taking immunosuppression medications, whether KT recipient or not) with the non-immunosuppressed participants, the former had significantly lower GMTs for all the HPV serotypes and lower seroconversion rates for HPV 6, 11, and 18. KT females had higher GMTs and seroconversion rates for certain serotypes. There were no adverse events in either group. Conclusions: HPV vaccine was well-tolerated in this population. Pediatric KT recipients had in general lower GMTs and seroconversion rates compared to their peers with CKD or on dialysis. Immunosuppression played a role in the lack of seroconversion. Our results emphasize the importance of advocating for HPV vaccination prior to KT and acknowledge its safety post transplantation. Future studies are needed to investigate the effect of a supplemental dose of HPV vaccine in KT recipients who do not seroconvert and to evaluate the long-term persistence of antibodies post-KT., (Copyright © 2020 Nailescu, Nelson, Verghese, Twombley, Chishti, Mills, Mahan, Slaven and Shew.)

Effective treatment modalities for diarrhea in solid organ transplant recipients are lacking. We evaluated the effect of oral IgG on clinical course of diarrhea in pediatric kidney transplant recipients. We retrospectively studied all pediatric kidney transplant recipients who required hospitalization for diarrhea between January 1, 2015, and December 31, 2017. We divided the recipients into two groups based on whether they had received oral IgG to treat diarrhea. Sixteen pediatric kidney transplant recipients required hospitalization for diarrhea over 3 years. Median age at admission was 9.25 years (IQR:12.54). Fifty-six percent of recipients were male, and 81% were white. Four patients received oral IgG for prolonged diarrhea. Oral IgG recipients had longer diarrheal duration before admission (median (days) 14.5 vs1; P .02), a trend for greater weight loss at admission (median (kilogram) 1.4 vs 0.2; P .3), and a trend for higher acute kidney injury (>75% reduction in glomerular filtration rate: 100% vs 42%; P .36). Diarrhea resolved completely in 3 (75%) oral IgG recipients and 7 (58%) non-oral IgG patients by discharge (P .99). One oral IgG recipient showed partial improvement but also had biopsy evidence of mycophenolate-induced colitis. All patients tolerated oral IgG well. No patients required re-hospitalization within 30 days of discharge. Oral IgG may be used safely and effectively to treat prolonged diarrhea in pediatric kidney transplant recipients. A larger, randomized, prospective study is needed to further assess the efficacy of oral IgG in the treatment of diarrhea., (© 2019 Wiley Periodicals, Inc.)

Objective: To assess practice pattern similarities and differences amongst pediatric rheumatologists and nephrologists in the management of pediatric Granulomatosis with Polyangiitis (GPA)., Methods: A voluntary survey was distributed to the Midwest Pediatric Nephrology Consortium Group (MWPNC) and an international pediatric rheumatology email listserv in 2016-2017. Data were collected on general practice characteristics and preferences for induction management under three clinical scenarios (A-C): newly diagnosed GPA with glomerulonephritis, GPA with rapidly progressive glomerulonephritis, and GPA with pulmonary hemorrhage. In addition, individual preferences for GPA maintenance medications, disease monitoring, and management of GPA with end-stage renal disease were ascertained., Results: There was a 68% response rate from the MWPNC membership and equal numbers of rheumatology respondents. Survey results revealed Rituximab plus Cyclophosphamide is a more common induction choice for rheumatologists than nephrologists in induction Scenarios A and B, whereas Cyclophosphamide is more commonly chosen by nephrologists in Scenario A. Plasmapheresis rates increased for Scenarios A, B, and C for both specialties, but were overall low. There was no clear consensus on the duration of maintenance therapy nor diagnostic work-up. Rheumatologists more frequently chose Rituximab for maintenance and induction compared to nephrologists. There was also a higher than expected proportion of Mycophenolate Mofetil use for both specialties., Conclusion: This survey has revealed important differences in the way that rheumatologists and nephrologists manage this disease. It highlights the need for well-designed clinical trials in pediatric GPA patients and reveals that both specialties must be represented during consensus-building and clinical trial design efforts.

Epstein-Barr virus (EBV) infects about 90% of adults worldwide. It is the main cause of infectious mononucleosis, which is observed most frequently in adolescents. The disease can last several weeks and is characterized by lymphocytosis, sore throat, lymphadenopathy, and fatigue. Exposure to oral secretions during deep kissing has been identified as the major source for primary EBV infection in adolescents. Oral secretions are also thought to be the source for younger children through intimate intact or sharing food and eating utensils, although this has not been confirmed. Unlike most acute viral illnesses such as influenza, the incubation period of symptomatic primary EBV infection is unusually long, lasting about six weeks. Diagnosis is typically made by heterophile antibody tests and/or EBV-specific antibody tests. Long-term consequences may result from acquisition of the virus, including nasopharyngeal carcinoma and lymphomas. Nevertheless, there remains a surprising dearth of knowledge regarding the establishment of an immune response to persistent EBV infection, especially during the incubation period. This lack of knowledge has impaired our ability to develop an effective prophylactic EBV vaccine, despite various attempts. Our greatest challenges in EBV research are to develop a prophylactic vaccine and devise treatment strategies for persons already infected with EBV., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Many pediatric centers utilize a variety of protocols including preemptive plasmapheresis to prevent the recurrence of FSGS post-transplant. But the effectiveness of this expensive, time-consuming process of plasmapheresis in the prevention of FSGS recurrence is still unclear. We retrospectively reviewed all pediatric cases of FSGS in our center that received a kidney transplant and compared the transplant and patient outcomes of those transplanted after 2006 who received pretransplant plasmapheresis to those prior to 2006 who did not. Of the 57 children with FSGS, 31 and 26 were transplanted before and after 2006, respectively. The cohorts differed significantly in keeping with the center immunosuppression protocol changes, and prior to 2006, the recipients were significantly younger. All children with FSGS transplanted after 2006 underwent three and one sessions of 1.0 plasma volume/exchange plasmapheresis with fresh frozen plasma replacement prior to the transplant in living and deceased donors, respectively, in addition to five sessions of every other day post-transplant pheresis. The incidence (27% vs 26%, P = 1.0) and time to recurrence of FSGS in the kidney allograft (P = .22) were not significantly different in patients that did and did not undergo prophylactic plasmapheresis. We need to re-evaluate the role of preemptive plasmapheresis in the prevention of FSGS recurrence in a prospective multicenter study., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The etiology and treatment of transplant glomerulopathy (TG) is not clear. TG is associated with donor-specific antibodies but the lack of C4d deposition in the peritubular capillaries (ptc-C4d) in some cases has caused the role of complement in the pathogenesis of TG to be debated. There is however, little information on C4d deposition in the glomerulus itself. We retrieved random frozen sections from 25 cases with well-established TG by light microscopy (LM) and 25 cases without TG as controls and reviewed the LM and immunofluorescence (nine biopsies were excluded due to inadequate samples). Glomerular complement deposition was assessed in all included biopsies. Glomerular C3d and C4d deposition occurred in a distinct pattern in all TG biopsies: segmental or global double linear staining of the glomerular capillary wall in 23 (100%). This pattern was not present in any NON-TG biopsies. The distinct glomerular complement deposition patterns in all TG cases are suggestive that TG is a proximal complement-mediated process and therapies should focus on proximal complement inhibition.

MMF is commonly prescribed following kidney transplantation, yet its use is complicated by leukopenia. Understanding the genetics mediating this risk will help clinicians administer MMF safely. We evaluated 284 patients under 21 years of age for incidence and time course of MMF-related leukopenia and performed a candidate gene association study comparing the frequency of 26 SNPs between cases with MMF-related leukopenia and controls. We matched cases by induction, steroid duration, race, center, and age. We also evaluated the impact of induction and SNPs on time to leukopenia in all cases. Sixty-eight (24%) patients had MMF-related leukopenia, of which 59 consented for genotyping and 38 were matched with controls. Among matched pairs, no SNPs were associated with leukopenia. With non-depleting induction, UGT2B7-900A>G (rs7438135) was associated with increased risk of MMF-related leukopenia (P = .038). Time to leukopenia did not differ between patients by induction agent, but 2 SNPs (rs2228075, rs2278294) in IMPDH1 were associated with increased time to leukopenia. MMF-related leukopenia is common after transplantation. UGT2B7 may influence leukopenia risk especially in patients without lymphocyte-depleting induction. IMPDH1 may influence time course of leukopenia after transplant., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Epstein-Barr virus (EBV) poses a significant threat to patient and graft survival post-transplant. We hypothesized that recipients who shed EBV at transplant had less immunologic control of the virus and hence were more likely to have active EBV infection and disease post-transplant. To test this hypothesis, we conducted a 5-year prospective study in primary solid organ transplant recipients. We measured EBV DNA in oral washes and blood samples by quantitative PCR before transplant and periodically thereafter for up to 4 years. Pre-transplant samples were available from 98 subjects. EBV DNA was detected pre-transplant in 32 of 95 (34%) and 5 of 93 subjects (5%) in oral wash and blood, respectively. Recipients with and without detectable pre-transplant EBV DNA were not significantly different demographically and had no significant difference in patient and graft survival (P = .6 for both comparisons) or post-transplant EBV viremia-free survival (P = .8). There were no cases of EBV-related disease or post-transplant lymphoproliferative disorder (PTLD) in any of the patients with detectable EBV DNA pre-transplant. In conclusion, detectable EBV DNA pre-transplant was not associated with differences in patient/graft survival, post-transplant EBV viremia, or EBV-related diseases including PTLD., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We previously demonstrated that detectable BKV replication in donor urine pretransplant was significantly associated with post-transplant recipient BKV viremia. In this 4-year prospective study, we assessed whether recipient BKV replication pretransplant was associated with post-transplant viremia/BKV nephropathy. We studied 220 primary adult and pediatric organ transplant recipients for 490 person-years and 2100 clinical visits. BKV viruria was detectable in 28 (16%), 26 adults and two children; and viremia in none pretransplant. Post-transplant viruria occurred in all recipients with pretransplant BKV viruria, significantly more than in recipients without pretransplant viruria on univariate (P<.005) and multivariate analysis including type of organ transplanted and immunosuppression type (P .008). Time to post-transplant viruria was significantly shorter in recipients with pretransplant viruria (P .01). By univariate and multivariate analysis, BKV viruria in recipients pretransplant did not impact post-transplant BKV viremia (P=.97 and .97, respectively) even when stratified by type of organ transplant (kidney P=.6; liver P=.5). The peak serum and urine BKV PCR post-transplant were not significantly different in patients with pretransplant BKV viruria and no one developed BK nephropathy. In conclusion, recipient BKV viruria prior to transplant predicts post-transplant viruria but not viremia or BKV nephropathy., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Pediatric patients requiring kidney transplant after hematopoietic cell transplant receive multiple courses of immunosuppression placing them at risk for infection. To elucidate potential risk factors for infection, we compared the immunosuppressive regimens and infectious complications of pediatric kidney transplant recipients at a single institution who had previously undergone hematopoietic cell transplant from different donors to similar patients reported in the literature. Among the initial four post-hematopoietic cell transplant kidney transplant patients reviewed, viremia episodes were universal, including BK virus, Epstein-Barr virus, and human herpesvirus-6, with one death from presumed BK virus encephalitis. No viremia was reported in five similar cases in the literature. Risk factors for increased infection include use of lymphodepleting serotherapy in HCT conditioning, multiple HCTs, limited immune reconstitution time between transplants, increased pre-KTx viral burden, and use of T-cell-depleting versus -suppressive induction immunosuppression for KTx. These findings suggest that pediatric post-HCT KTx recipients are at increased risk for viral infections, likely benefitting from thorough pre-KTx evaluation of immune reconstitution and preferential use of non-T-cell-depleting induction therapy for KTx. We applied these recommendations to one subsequent post-HCT patient requiring KTx at our institution with excellent outcomes one year post-KTx., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Successful renal transplantation is the optimal treatment for chronic kidney failure, but this was not always so for children. Beginning with the first kidney transplants in the 1950s, children experienced poorer patient and graft survival rates than adult patients. But over the last 6 decades, an improved understanding of the immune system which has steered pediatric multi-center clinical/pharmacokinetic and mechanistic studies that have sculpted our immunosuppression with markedly better patient and graft survivals. In addition, uniquely pediatric issues related to growth, development, neurocognitive maturation, increased complications from primary viral infections, and comorbid congenital/inherited disorders, are now diagnosed and effectively managed in these children. Refined pretransplant preparation (vaccinations for preventable diseases, attention to cognitive delays, effective dialysis and nutrition) improved donor selection, and more potent immunosuppression have all contributed to enhanced outcomes. Similarly, improvements in pediatric surgical techniques, postoperative care and better antiviral prophylaxis have all shortened hospitalizations and reduced morbidity. Today pediatric kidney transplant outcomes are markedly improved and younger children today experience better long-term graft survival than adults! While difficult problems remain, we have made tremendous progress and anticipate even more advances in the future of pediatric kidney transplantation.

Background: Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections are a significant cause of morbidity and mortality in transplant recipients and are often transmitted from the donor organ., Methods: In a pilot prospective, randomized, double-blinded, placebo-controlled trial, we studied whether 14 days of pretransplant donor treatment with valganciclovir (valG) versus placebo reduced donor-to-recipient transmission, making posttransplant recipient prophylaxis more effective in reducing EBV and CMV disease., Results: Seventeen D+ R- donor-recipient pairs were enrolled: 7 and 10 donors were randomized to valG and placebo, respectively. At study initiation, no donor had detectable CMV replication, five had EBV replication (two in valG, three in placebo group): EBV replication was undetectable during valG treatment, but resumed on stopping valG. Valganciclovir was tolerated without side effects or leukopenia. All recipients received routine posttransplant viral prophylaxis with valG. For recipients, viremia-free survival time, incidence, range, peak, and duration of CMV and EBV viremia were not significantly different between groups. There was no disease in the valG group but two serious viral diseases occurred in the placebo group (one CMV; one EBV-related posttransplant lymphoproliferative disorder). In the case of posttransplant lymphoproliferative disorder, the EBV DNA from the donor's oral wash and the recipient's lymphoid tissue biopsy had identical latent membrane protein 1 (LMP-1) sequence variations from the reference EBV strain, making it highly probable that the recipient's virus was of donor origin., Conclusion: Based on this pilot trial, we recommend an adequately powered study to determine if pretransplant donor treatment with valG can reduce posttransplant CMV and EBV disease with merely routine posttransplant recipient viral prophylaxis.

Background: Organ donors are often implicated as the source of posttransplant recipient infection. We prospectively studied kidney and liver donor-recipient pairs to determine if donor viral replication of cytomegalovirus (CMV), Epstein-Barr virus (EBV), and BK polyomavirus (BKV) at transplant was a risk factor for posttransplant recipient infection and disease., Methods: Donors and recipients were studied for antibodies against CMV and EBV and for quantitative viral replication of CMV, EBV, and BKV in oral washes, urine, and whole blood pretransplant. Recipient testing continued every 3 months after transplantation. Demographic and clinical data on infections and graft and subject outcomes were obtained., Results: The 98 donor-recipient pairs included 15 liver and 83 kidney transplants (18 of whom were children). No donor had detectable CMV replication; therefore, its impact on recipient CMV replication could not be analyzed. Donor EBV replication occurred in 22%, mostly in the oral wash and showed no impact on posttransplant recipient EBV replication (P=0.9) or EBV viremia (P=0.6) in kidney or liver recipients. Donor BKV replication occurred in 17%, mostly in the urine and although not associated with posttransplant recipient urinary BKV replication in recipients, it was associated with BKV viremia (P=0.02), and a significantly shorter time to BKV viremia (P=0.01) in kidney recipients., Conclusion: Donor replication of CMV or EBV did not impact posttransplant recipient viral replication in kidney or liver transplants. Donor urinary BKV replication is associated with recipient BKV viremia in kidney transplants.

Contrast-induced nephropathy (CIN) remains a common and potentially serious complication in at risk patients after exposure to contrast agents. Risk factors for CIN include chronic kidney disease, hypotension, diabetes mellitus, recent previous exposure to contrast and all of these are potentially additive. Therefore, careful pre-procedural risk stratification is important. In high-risk patients, contrast should be avoided if possible. If avoidance is not possible, the volume of contrast should be minimized and the type of contrast used should if possible be non-ionic iso-osmolar contrast. In view of the clinical importance of CIN, numerous potential risk-reduction strategies have been evaluated. Adequate intravenous volume expansion with isotonic crystalloid (1.0-1.5 mL/kg per hr) for 3-12 hr before the procedure and continued for 6-24 hr afterward can lessen the probability of CIN in patients at risk. But there are insufficient data on oral fluids as a preventive strategy. Nephrotoxic drugs should be withdrawn before contrast administration in patients at risk for CIN. No adjunctive medical or mechanical treatment has been proved to be efficacious in reducing risk for CIN including prophylactic hemodialysis and hemofiltration, N-acetylcysteine, fenoldopam, dopamine, calcium channel blockers, atrial natriuretic peptide, and L-arginine. The CIN Consensus Working Panel considered that, of the pharmacologic agents that have been evaluated, theophylline, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), ascorbic acid, and prostaglandin E deserve further evaluation.

Neutropenic fever is a common complication of myelosuppressive therapy in pediatric oncology patients. Piperacillin-tazobactam (PIP/TAZO) is a broad spectrum antibiotic used for empiric treatment of neutropenic fever. We describe four cases of suspected PIP/TAZO induced nephrotoxicity occurring in children with pediatric malignancies admitted to the hospital and treated for fever ± neutropenia. All patients exhibited acute renal injury shortly after PIP/TAZO administration with one of these cases having biopsy evidence of acute interstitial nephritis. These findings are suggestive of PIP/TAZO induced nephrotoxicity in pediatric oncology patients with fever ± neutropenia and that PIP/TAZO should be used judiciously in this population., (© 2013 Wiley Periodicals, Inc.)

Background: Given the nephrotoxicity of calcineurin inhibitors (CNIs), we asked whether their addition improved living related donor (LRD) human leukocyte antigen (HLA) identical kidney transplant recipient outcomes., Methods: We performed a comprehensive literature review and a single-center study comparing patient survival (PS) and graft survival (GS) of LRD HLA-identical kidney transplants for three different immunosuppression eras: Era 1 (up to 1984): anti-lymphocyte globulin (ALG) induction and maintenance immunosuppression with prednisone and azathioprine (AZA) (n = 114); Era 2a (1984-99): CNI added; evolution from ALG to thymoglobulin; AZA to mycophenolate (n = 262). Era 2b (1999-2011): rapid discontinuation of prednisone (thymoglobulin induction, CNI and mycophenolate) in recipients having first or second transplant and not previously on prednisone (n = 77)., Results: Demographics differed by era: recipient (P < 0.0001) and donor age (P < 0.0001) increased and the proportion of Caucasian donors (P = 0.02) and recipients (P = 0.003) decreased with each advancing era. There was no significant difference in PS (P = 0.6); cause of death (P = 0.5); death-censored GS (P = 0.8) or graft loss from acute rejection by era. Graft loss from chronic allograft nephropathy (P = 0.02) and hypertension (P = 0.005) were greater in the CNI eras. There were no significant differences in the 1/creatinine slopes between eras for the first (P = 0.6), second (P = 0.9) or >2 years post-transplant (P = 0.4). Literature review revealed no clear benefits for CNI in these human leukocyte antigen (HLA) identical LRD graft recipients., Conclusions: This study confirmed that there are no benefits of CNIs for HLA-identical LRD recipients. Moreover, we did find evidence of potential harm. Thus, monotherapy or early discontinuation of CNI should be given consideration in these patients.

Novel therapies are urgently needed for the management of cytomegalovirus (CMV) disease in high-risk patients. Currently licensed agents target the viral DNA polymerase, and although they are effective, they are fraught with toxicities to patients. Moreover, emergence of antiviral resistance is an increasing problem, particularly for patients on long-term suppressive therapy. A new agent, letermovir (AIC246), shows great promise for the management of CMV infection. Advantages include its good oral bioavailability, its lack of toxicity, and the apparent absence of drug-drug interactions. Letermovir has a novel mechanism of action, exerting its antiviral effect by interfering with the viral pUL56 gene product and in the process disrupting the viral terminase complex. This agent demonstrates substantial promise as an alternative to more toxic antivirals in patients at high risk for CMV disease, particularly in the transplantation setting.

BKV has emerged as a significant pathogen in the field of transplantation, predominantly causing BKV nephropathy in renal transplant recipients and hemorrhagic cystitis in HSCT recipients. However, case reports describe more diverse complications, and we too present three unusual cases of BKV infections in pediatric renal transplant recipients. First, we describe a case of biopsy-proven renal damage secondary to BKV prior to the onset of viremia, demonstrating that BKV nephropathy can occur without preceding viremia. We also present two renal transplant recipients with persistent BK viruria, one with BKV-associated hemorrhagic cystitis and the other with microscopic hematuria. Therefore, we conclude that BKV manifestations may be more diverse than previously thought and suggest clinical utility in urine BKV qPCR testing in specific transplant recipients., (© 2012 John Wiley & Sons A/S.)

Little is published regarding the effect of advertising for kidney donors on transplant centers. At our center, families of nine children used media appeals. Per candidate, there were 8 to 260 potential donor calls, 92 (11.6%) were medically ineligible, 326 (41.1%) voluntarily did not proceed or an alternate donor had been approved, 38 (4.8%) were ABO incompatible, and 327 (41.1%) had positive crossmatch or unsuitable human leukocyte antigens. Media appeals resulted in four living donor transplants and five nondirected donors to other candidates, and we made directed changes in our center. The ethical debate of advertising for organ donors continues.

SAB assays have increased the sensitivity and specificity to detect HLA alloantibodies, but there is uncertainty about the clinical relevance of SAB-positive alloantibodies when the FCXM is negative. We performed a retrospective study to evaluate the clinical significance of SAB-detected DSA in 82 pediatric recipients of a first kidney transplant between January 2000 and December 2005 who had a negative pretransplant FCXM. Pretransplant sera were evaluated by SAB for DSA. Graft loss and rejection between patients with (DSA+) and without DSA (DSA-) were compared. DSA were detected in 13.9%. Eighty percent of DSA+ subjects were DD transplant recipients vs. 56.9% in the DSA- cohort. The RR of graft loss in DSA+ vs. DSA- was 3.3 (95% CI, 1.4-7.9) and in DD was 4.3 (95% CI 1.4-13.1). By Cox regression, the HR of graft loss in DSA+ vs. DSA- was 2.8 (95% CI 0.7-10.9; p = 0.14) and in DD was 5.1 (95% CI 1-25.6; p = 0.05). Acute rejection occurred in 60% in the DSA+ vs. 44.4% in DSA- (p = 0.5). SAB-detected DSA was associated with impaired renal allograft survival in pediatric renal transplant recipients. Impaired graft survival in pediatric renal transplant recipients with DSA detected by solid-phase assays.

BK nephropathy is a known cause of renal insufficiency in kidney transplant recipients. Activation of the polyoma virus may also occur in the native kidneys of non-renal allograft recipients. BK nephropathy has only been reported in a few patients after HCT, most being adult patients, and the single reported pediatric case had evidence of hemorrhagic cystitis. The response to antiviral therapy also seems to differ widely. Here, we describe two cases of BK nephropathy in the native kidneys of HCT recipients exposed to high levels of immunosuppression because of GVHD. Neither of our patients had any evidence of hemorrhagic cystitis. We present definitive renal pathology and detailed chronological evidence of the rising serum creatinine with simultaneous serum and urine BK PCR titers. In one of our cases, antiviral therapy did not seem beneficial as documented by continued renal dysfunction and elevated serum/urine BK PCR titers. Based on our report, intense immunosuppression in pediatric HCT recipients seems to be involved in the activation of BK virus and BK nephropathy should be suspected even in the absence of hematuria in HCT recipients with unexplained renal dysfunction.