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Background: BK polyomavirus (BKV) DNAemia is a challenging infectious complication after kidney transplant (KT). Reduction of immunosuppression is the mainstay of management, and tacrolimus is often the first immunosuppressive medication adjusted upon the diagnosis of BKV DNAemia. This study aimed to evaluate the impact of a new institutional protocol with lower target tacrolimus levels on BKV DNAemia, allograft rejection, and de novo donor-specific antibodies (dnDSA) among pediatric KT recipients., Methods: We conducted a retrospective chart review of all KT episodes between January 2013 and December 2018. The new protocol with lower target tacrolimus levels was implemented in March 2015. One hundred twenty-seven patients were included in primary analysis. All patients received induction with basiliximab and methylprednisolone and were maintained on a steroid-based immunosuppressive regimen., Results: In the post-intervention cohort, cumulative incidence of BKV DNAemia at 100 days (13.4% vs. 17.8%, p = .605) and 18 months post-KT (34.1% vs. 26.7%, p = .504) was not significantly different from the pre-intervention cohort. Biopsy-proven rejection rate did not change. However, we observed a trend toward earlier development of dnDSA in the post-intervention cohort using the Kaplan-Meier survival analysis (log-rank p = .06). Younger recipient age at the time of transplant was found to slightly increase the risk of BKV DNAemia (OR: 1.09, 95% CI [1.01, 1.16], p = .024). There was an association between BKV DNAemia and biopsy-proven rejection of any type ( adjusted OR: 2.77, 95% CI [1.26, 6.23], p = .012), especially acute T-cell-mediated rejection grade 1A and above ( adjusted OR: 2.95, 95% CI [1.06, 8.30], p = .037), after adjusted for recipient age at the time of transplant., Conclusions: Targeting lower tacrolimus levels did not decrease the incidence of BKV DNAemia within 100 days or 18 months post-KT, nor did it increase the risk of biopsy-proven rejection among pediatric KT recipients in our center. However, there was a trend toward earlier development of dnDSA, which may portend worse long-term graft outcome post-KT. Our findings highlight the need for individualized immunosuppressive regimens based on immunologic and infectious risk factors and the importance of implementing innovative biomarkers to guide therapy and improve outcomes., (© 2024 Wiley Periodicals LLC.)

Background: Antibody-mediated rejection (AMR) is a major cause of kidney allograft loss. There is a paucity of large-scale pediatric-specific data regarding AMR treatment outcomes., Methods: Data were obtained from 14 centers within the Pediatric Nephrology Research Consortium. Kidney transplant recipients aged 1-18 years at transplant with biopsy-proven AMR between 2009 and 2019 and at least 12 months of follow-up were included. The primary outcome was graft failure or an eGFR <20 mL/min/1.73 m 2 at 12 months following AMR treatment. AMR treatment choice, histopathology, and DSA class were also examined., Results: We reviewed 123 AMR episodes. Median age at diagnosis was 15 years at a median 22 months post-transplant. The primary outcome developed in 27.6%. eGFR <30 m/min/1.73 m 2 at AMR diagnosis was associated with a 5.6-fold higher risk of reaching the composite outcome. There were no significant differences in outcome by treatment modality. Histopathology scores and DSA class at time of AMR diagnosis were not significantly associated with the primary outcome., Conclusions: In this large cohort of pediatric kidney transplant recipients with AMR, nearly one-third of patients experienced graft failure or significant graft dysfunction within 12 months of diagnosis. Poor graft function at time of diagnosis was associated with higher odds of graft failure., (© 2024 Wiley Periodicals LLC.)

In this review, we describe the multidisciplinary, multidimensional care required to optimize outcomes for pediatric transplant recipients with rare genetic kidney diseases. Transplant success, recipient survival, and improvement in quality of life depend on collaboration between patients, families, and a team of specialists with medical, as well as nonmedical expertise. A multidisciplinary transplant team composed of experts from medicine, surgery, nursing, nutrition, social services, transplant coordination, psychology, and pharmacology, is now standard in most transplant centers and is critical to the success of a transplant. In addition to these professionals, other specialists, such as cardiologists, urologists, geneticists, metabolic disease specialists, occupational therapists, case management, child life, chaplain, and palliative care services, have a crucial role to play in the preparation, surgery, and follow-up care, especially when a pediatric patient has a rare genetic disorder leading to renal involvement, and the need for transplantation. In order to describe this multidisciplinary care, we divide the genetic renal diseases into five subgroups-metabolic and tubular disorders, glomerular diseases, congenital anomalies of the kidney and urinary tract, ciliopathies including cystic diseases, and miscellaneous renal conditions; and describe for each, the need for care beyond that provided by the standard transplant team members., (© 2023 Wiley Periodicals LLC.)

Background: Cytomegalovirus (CMV) is associated with morbidity and mortality in solid organ transplant recipients (SOTR). Valganciclovir (VGC) is extensively used for prophylaxis. Optimal dosing in children, risk factors for failure, and the impact of dose adjustments on CMV DNAemia is not well established., Methods: This retrospective cohort study of pediatric SOTR transplanted between 2010-2018 evaluated the epidemiology of CMV DNAemia and used Cox-regression to assess the risk factors for CMV DNAemia within one-year following SOTR., Results: In 393 pediatric SOTR (heart [96, 24.4%], kidney [180, 45.6%], liver [117, 29.8%]; median age 9.5 ± 0.3 years), overall CMV DNAemia incidence was 6.6/10 000 days (95%CI 5.1/10 000-7.9/10 000) and varied by organ groups: heart 8.2/10 000 days (95%CI 4.9/10 000-11.4/10 000), kidney 5.8/10 000 days (95%CI 3.9/10 000-7.8/10 000), liver 6.2/10 000 days (95%CI 3.7/10 000-8.7/10 000). CMV DNAemia was detected in 75 of 275 (27.2%) patients who received prophylaxis (40 cases occurred during prophylaxis and 35 occurred after completion of prophylaxis). The median VGC dose given according to institutional weight-based algorithm was approximately 1.5-fold lower than the manufacturer-recommended dose. This discordance was more prominent at younger age groups (3.2-fold lower in <2-year-old [100 mg versus 325 mg], 2.5-fold lower in <6-year-old [200 mg versus 447 mg]). Dose reduction due to adverse events was an independent risk factor for breakthrough CMV DNAemia (hazard ratio 2.2, 95%CI 1.2-3.8) among patients with similar age, CMV risk stratification, starting VGC dose, immunosuppressive therapy, and organ group., Conclusion: CMV events occurred while on VGC prophylaxis. Weight-based VGC may prevent supratherapeutic VGC exposure especially in younger children. Dose reduction of VGC prophylaxis for adverse event management places patients at an increased risk for CMV DNAemia suggesting other agents with fewer adverse effects should be considered and need to be studied in children., (© 2023 Wiley Periodicals LLC.)

Background: Kidney transplantation (KT) is the preferred treatment for children with end-stage kidney disease. Recent advances in immunosuppression and advances in donor specific antibody (DSA) testing have resulted in prolonged allograft survival; however, standardized approaches for surveillance DSA monitoring and management of de novo (dn) DSA are widely variable among pediatric KT programs., Methods: Pediatric transplant nephrologists in the multi-center Improving Renal Outcomes Collaborative (IROC) participated in a voluntary, web-based survey between 2019 and 2020. Centers provided information pertaining to frequency and timing of routine DSA surveillance and theoretical management of dnDSA development in the setting of stable graft function., Results: 29/30 IROC centers responded to the survey. Among the participating centers, screening for DSA occurs, on average, every 3 months for the first 12 months post-transplant. Antibody mean fluorescent intensity and trend most frequently directed changes in patient management. Increased creatinine above baseline was reported by all centers as an indication for DSA assessment outside of routine surveillance testing. 24/29 centers would continue to monitor DSA and/or intensify immunosuppression after detection of antibodies in the setting of stable graft function. In addition to enhanced monitoring, 10/29 centers reported performing an allograft biopsy upon detection of dnDSA, even in the setting of stable graft function., Conclusions: This descriptive report is the largest reported survey of pediatric transplant nephrologist practice patterns on this topic and provides a reference for monitoring dnDSA in the pediatric kidney transplant population., (© 2023 The Authors. Pediatric Transplantation published by Wiley Periodicals LLC.)

The adoption of de novo belatacept in kidney transplant (kTx) recipients was hampered by an increased risk of acute cellular rejection (ACR) with variation in adopted belatacept based immunosuppressive therapies across centers. We used data from the Scientific Registry of Transplant Recipients (SRTR) to evaluate the temporal trends in belatacept use and describe the associated induction and maintenance regimens in US adult kTx recipients transplanted between June 2011 and December 2018. The number of patients receiving de novo-belatacept based immunosuppressive therapy increased from .74% in 2011 to 3.11% in 2016. In 2016, 66/207 centers used de novo belatacept-based regimen with 3.03% using it in over 50% of their patients. The use of T-cell depleting agents increased with time. Since 2012, the rate of calcineurin inhibitor (CNI) use in combination with belatacept remained stable around 50% and ∼30% remained under belatacept/CNI combination at 1-year post-transplantation. The adoption of belatacept as de novo immunosuppressive regimen has been slow and its use remains low in the United States. Various regimens have been used to modulate the risk of ACR. Further studies evaluating the long-term outcomes of these regimens and assessing their safety especially with regard to the risk of infection are needed., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Recurrent focal and segmental glomerulosclerosis (FSGS) in kidney transplant recipients is associated with lower graft survival and increased morbidity. There are limited data to guide the decision to re-transplant patients with transplant failure due to FSGS recurrence. We aimed to evaluate outcomes in patients re-transplanted after having initial graft failure due to recurrent FSGS and to study physician attitudes and practice patterns., Methods: Retrospective data from 10 centers were collected on 20 patients transplanted between January 1997 and September 2018. A survey was sent to nephrologist members of the Pediatric Nephrology Research Consortium., Results: Mean patient age (years) was 9.8 ± 4.8 at first transplant and 15.9 ± 4.9 at re-transplantation. Pre-transplant plasmapheresis was used in 1 (5.3%) primary transplant vs. 7 (38.9%) re-transplants (p = .03). Nephrotic syndrome recurred in 14 patients (70%) after re-transplantation and was severe in 21.1% vs. 64.7% after first transplant (p = .04). Graft survival was significantly higher in the second transplant (p .009) with 70% having functioning grafts at a median of 25.2 months. Thirty-one physicians from 21 centers completed the survey, 94% indicated they would re-transplant such patients, 44.4% preferred a minimum waiting period before re-transplantation, 36.4% preferred living donors, and 22.2% indicated having protocols for re-transplantation at their centers., Conclusions: Consideration for re-transplantation is high among pediatric nephrologists. Pre-transplant plasmapheresis was more frequent in re-transplanted patients. Nephrotic syndrome recurrence was less severe, with better graft survival. More data and a larger population are necessary to further evaluate outcome determinants and best practices in this special population., (© 2021 Wiley Periodicals LLC.)

Introduction: There are limited data to guide optimal treatment strategies for acute cellular rejection (ACR) based on Banff grade for pediatric kidney transplant recipients. This report reviews a large pediatric transplant center's experience with ACR., Materials and Methods: A retrospective analysis of pediatric kidney transplant recipients at our center from 2007 to 2014 was performed. Primary outcomes were incidence of graft failure and graft function one year following ACR based on Banff grade and treatment received., Results: A total of 204 patients were reviewed, of which 65 received rejection treatment with either an oral steroid cycle (n = 16), intravenous steroid pulse (n = 28), or anti-thymocyte globulin (rATG, n = 21). Overall, patients received rATG for treatment of more severe rejection associated with impaired graft function and as a group experienced statistically significant improvements in eGFR over the year following treatment, though most did not regain baseline graft function., Discussion: Our data suggest that rATG is partially effective in treating ACR, but our study was underpowered to determine the effect of different treatments based on Banff grade. Since there is limited literature to guide clinical treatment of ACR in children, large transplant centers should collaborate to evaluate outcomes and establish evidence-based practice., (© 2018 Wiley Periodicals, Inc.)

Background: Optimizing graft survival and diminishing human leukocyte antigen (HLA) sensitization are essential for pediatric kidney transplant recipients. More precise HLA matching predicting epitope mismatches could reduce alloreactivity. We investigated the association of predicted HLA B- and T-cell molecular mismatches with the formation of de novo donor-specific antibodies, HLA antibodies, rejection, and graft survival., Methods: Forty-nine pediatric kidney transplant recipients transplanted from 2009 to 2020 were retrospectively studied. Donors and recipients were high-resolution HLA typed, and recipients were screened for HLA antibodies posttransplant. HLA-EMMA (HLA Epitope MisMatch Algorithm) and PIRCHE-II (Predicted Indirectly ReCognizable HLA Epitopes) predicted the molecular mismatches. The association of molecular mismatches and the end-points was explored with logistic regression., Results: Five recipients (11%) developed de novo donor-specific antibodies. All five had de novo donor-specific antibodies against HLA class II, with four having HLA-DQ antibodies. We found no associations between PIRCHE-II or HLA-EMMA with de novo donor-specific antibodies, HLA sensitization, graft loss, or rejection. However, we did see a tendency towards an increased odds ratio in PIRCHE-II predicting de novo donor-specific antibodies formation, with an odds ratio of 1.12 (95% CI: 0.99; 1.28) on HLA class II., Conclusion: While the study revealed no significant associations between the number of molecular mismatches and outcomes, a notable trend was observed - indicating a reduced risk of dnDSA formation with improved molecular match. It is important to acknowledge, however, that the modest population size and limited observed outcomes preclude us from making definitive conclusions., (© 2024 The Authors. Pediatric Transplantation published by Wiley Periodicals LLC.)

Background: There have been over 51 000 pediatric solid organ transplants since 1988 in the United States alone, leading to a growing population of long-term survivors who face complications of childhood organ failure and long-term immunosuppression., Aims: This is an educational review of existing literature., Results: Pediatric solid organ transplant recipients are at increased risk for risk for cardiovascular and kidney disease, skin cancers, and growth problems, though the severity of impact may vary by organ type. Pediatric recipients often are able to complete schooling, maintain a job, and form family and social networks in adulthood, though at somewhat lower rates than the general population, but face additional challenges related to neurocognitive deficits, mental health disorders, and discrimination., Conclusions: Transplant centers and research programs should expand their focus to include long-term well-being. Increased collaboration between pediatric and adult transplant specialists will be necessary to better understand and manage long-term complications., (© 2024 The Authors. Pediatric Transplantation published by Wiley Periodicals LLC.)

Background: Long-term outcomes in pediatric kidney transplantation remain suboptimal, largely related to chronic rejection. Creatinine is a late marker of renal injury, and more sensitive, early markers of allograft injury are an active area of current research., Methods: This is an educational review summarizing existing strategies for monitoring for rejection in kidney transplant recipients., Results: We summarize supporting currently available clinical tests, including surveillance biopsy, donor specific antibodies, and donor-derived cell free DNA, as well as the potential limitations of these studies. In addition, we review the current avenues of active research, including transcriptomics, proteomics, metabolomics, and torque tenovirus levels., Conclusion: Advancing the use of noninvasive immune monitoring will depend on well-designed multicenter trials that include patients with stable graft function, include biopsy results on all patients, and can demonstrate both association with a patient-relevant clinical endpoint such as graft survival or change in glomerular filtration rate and a potential timepoint for intervention., (© 2024 The Authors. Pediatric Transplantation published by Wiley Periodicals LLC.)

Background: Kidney transplant (KT) was initially associated with poor outcomes, especially in smaller recipients. However, pediatric transplantation has evolved considerably over time. We investigated the impact of weight at the time of transplant and whether outcomes changed over 25 years for <10 kg recipients., Methods: Using the UNOS database, pediatric recipient outcomes were analyzed between 1/1/99 and 12/31/14. KT weight was stratified: <8.6 kg (mean weight of recipients <10 kg), 8.6-9.9 kg, 10-14.9 kg, 15-29.9 kg, and ≥30 kg. Outcomes in recipients <10 kg were then compared between 1990-1999 and 2000-2014., Results: 17 314 pediatric KT recipients were included; 518 (3%) had a transplant weight <10 kg. The highest rates of allograft loss and death were in recipients <8.6 kg and ≥30 kg. Recipients <8.6 kg also had higher rates of delayed graft function, rejection, and longer hospital length of stay. In the multivariable Cox regression model, transplant weight was not a predictor of allograft loss. When compared with recipients <8.6 kg, patient survival hazard ratios associated with recipient weight of 10-14.9 kg, 15-29.9 kg, and ≥30 kg were 0.61 (95%CI: 0.4, 1), 0.42 (95%CI: 0.3, 0.7) and 0.32 (95%CI: 0.2, 0.6), respectively. In the later era of transplant, recipients <10 kg had improved outcomes on univariate analysis; however, the era of transplantation was not an independent predictor of allograft loss or patient survival in Cox regression models., Conclusions: Outcomes in children weighing 8.6-9.9 kg at the time of KT were similar to higher weight groups and improved over time; however, special precautions should be taken for recipients <8.6 kg at the time of transplant., (© 2023 The Authors. Pediatric Transplantation published by Wiley Periodicals LLC.)

Background: Kidney transplantation (KT) is the best therapy in children with end-stage renal disease (ESRD), however, improving long-term graft survival remains challenging. The aim of this study was to determine graft survival and potential risk factors in pediatric patients who undergo deceased donor KT with a steroid-based regimen., Methods: The medical records of children who underwent their first deceased donor KT in Srinagarind Hospital (Khon Kaen, Thailand) between 2001 and 2020 were reviewed., Results: Seventy-two patients were studied. Male adolescents were the predominant recipients and the majority of donors were young adult males. Non-glomerular disease, particularly hypoplastic/dysplastic kidney disease, was the major cause of ESRD (48.61%). The mean cold ischemic time (CIT) was 18.29 ± 5.29 h. Most of the recipients had more than 4 human leukocyte antigen (HLA) mismatched loci with positive HLA-DR mismatch (52.78%). Induction therapy was administered in 76.74% of recipients. Tacrolimus plus mycophenolate sodium and prednisolone was the most common immunosuppressive maintenance regimen (69.44%). Graft failure occurred in 18 patients, mostly due to graft rejection (50%). Graft survival at 1, 3, and 5 years after KT were 94.40%, 86.25%, and 74.92%, respectively. The only significant risk factor of graft failure in this study was delayed graft function (DGF) (adjusted HR = 3.55; 95%CI: 1.14, 11.12; p = .029). Patient survival at 1, 3, and 5 years was 100%, 98.48%, and 96.19%, respectively., Conclusion: The short-term outcomes of pediatric KT from deceased donors were satisfactory; however, prevention of DGF would result in better outcomes., (© 2023 Wiley Periodicals LLC.)

Background: Incomplete resolution of T cell-mediated rejection (TCMR) after treatment may not be detected with serum creatinine monitoring and is associated with donor-specific antibodies and chronic rejection. We evaluate the utility of follow-up biopsies (FUB) to identify and characterize rates of persistent TCMR after treatment in pediatric kidney transplant patients., Methods: Patients from two pediatric transplant centers performing standard of care FUB at 1.5-2 months after treatment for TCMR were included. FUB were evaluated for extent of rejection resolution (complete vs. incomplete) and grade. Clinical data at time of FUB and later were reported, where available., Results: Fifty-eight patients underwent FUB, at mean of 1.7 months (SD 0.7) post-index biopsy. Rejection grade on index biopsy was Banff borderline (≥i1t1 and

This viewpoint aims to "set the stage" and provide the rationale for the proposed development of a large-scale, comprehensive survey assessing transplant patients' perceived unmet immunosuppressive therapy needs. Research in organ transplantation has historically focused on reducing the incidence and impact of rejection on allograft survival and minimizing or eliminating the need for chronic immunosuppressive therapies. There has been less emphasis and investment in therapies to improve patient-reported outcomes including health-related quality of life and side-effects. Patient-focused drug development (PFDD) is a new and important emphasis of the Food and Drug Administration (FDA) that provides a guiding philosophy for incorporating the patient experience into drug development and evaluation. The American Society of Transplantation (AST) Board of Directors commissioned this working group to prepare for the conduct of a comprehensive patient survey assessing unmet immunosuppressive therapy needs. This paper aims to describe the basis for why it is important to conduct this survey and briefly outline the plan for broad stakeholder engagement to ensure the information gained is diverse, inclusive, and relevant for advancing PFDD in organ transplant recipients., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: FSGS is a common indication for kidney transplant with a high-risk of posttransplant recurrence., Methods: In this review, we summarize current knowledge about FSGS recurrence after kidney transplantation, including epidemiology, pretransplant planning, posttransplant management, and investigational treatments., Results: FSGS recurs in 14%-60% of first transplants, likely associated with a circulating permeability factor. Pretransplant counseling regarding recurrence is critical, and patients with FSGS should undergo pretransplant genetic screening. Rapid progression to ESKD, initial steroid responsiveness, younger age at diagnosis, race/ethnicity, and mesangial hypercellularity or minimal change histology on native biopsy may be associated with recurrence. Living donation is not contraindicated but does not result in improved graft survival relative to deceased donation. Pretransplant nephrectomy may be performed for a variety of reasons, but does not decrease recurrence. Pretransplant therapy with rituximab and/or PE is understudied but not clearly effective at preventing recurrence. Patients with FSGS typically present early with rapid-onset severe proteinuria. Diagnosis can be confirmed by biopsy showing foot process effacement; typical FSGS lesions are not seen on light microscopy in the early stages. There is no established effective treatment for recurrent FSGS, but renin-angiotensin-aldosterone system inhibition and extracorporeal therapies, including PE and IA, are most commonly used. Adjunct or alternative therapies may include rituximab, lipopheresis, and cyclosporine., (© 2022 The Authors. Pediatric Transplantation published by Wiley Periodicals LLC.)

Background: The UK Renal Registry is responsible for the national collection and reporting of data on all children receiving long-term kidney replacement therapy [KRT], including kidney transplantation., Methods: All 13 UK pediatric nephrology centers contributed to providing individual patient data from the pediatric population incident to and prevalent to KRT as per the date 31 December 2018. Data for children aged 16-<18 years were presented separately as some were managed under adult care settings with different methods of data collection. Demographics and biochemical data, including kidney function and prevalence of cardiovascular risk factors [hypertension, hypercholesterolemia, BMI] were reported., Results: Eight hundred and twenty-six children (65.4 per million age-related population [pmarp]) and 199 young people (139.4pmarp) in the United Kingdom were prevalent to KRT on 31 December 2018. Overall, the incidence of KRT during 2018 was 9.1 pmarp and 12.6 pmarp in children and young people, respectively. Congenital anomalies of the kidney and urinary tract (CAKUT) were the most prevalent primary diagnoses (52%). Living and deceased donor transplantation was the most common treatment modality (78%). Patients on dialysis had lower age standardized mean height and weight ranges recorded in comparison to transplant patients [median height z score -1.8 vs. -1.1]. 73.1% patients had one or more cardiovascular disease risk factors., Conclusions: This study highlights increasing prevalence of hemodialysis and living donor transplantation as modalities for KRT. Of those incident to KRT, the highest patient survival was seen among 8-12 years and lowest <2 years. Moreover, there was a demographic shift from Caucasian toward Asian/other ethnicity and from CAKUT to other primary kidney diseases., (© 2022 Wiley Periodicals LLC.)

Background: Post-transplant lymphoproliferative disease (PTLD) is a life-threatening complication in renal transplant recipients. Immunomodulatory and chemotherapeutic treatment potentially affect allograft function. The aim of this study was to evaluate graft function of pediatric kidney transplant recipients following diagnosis and standardized treatment of PTLD., Methods: Patients were identified from the German Ped-PTLD registry, and data on renal function were retrospectively retrieved from patient charts. For PTLD treatment, immunosuppressive therapy was reduced and all children received rituximab (375 mg/m 2 ) for up to six doses. Two patients required additional low-dose chemotherapy. Renal allograft function was monitored by consecutive measurements of estimated glomerular filtration rate (eGFR) at defined time points. Follow-up was up to 60 months after PTLD., Results: Twenty patients were included in this cohort analysis. Median time from transplantation to PTLD was 2.4 years. Histopathology showed monomorphic lesions in 16 and polymorphic in 4 patients. Two patients experienced PTLD relapse after 2 and 14 months. Range-based analysis of variance showed stable allograft function in 17 of 20 patients (85%). Mean eGFR increased during early treatment phase. One patient experienced graft rejection 5.3 years after diagnosis of PTLD. Another patient developed recurrence of primary renal disease (focal-segmental glomerulosclerosis) and lost his renal allograft 3.8 years post-transplant (2.0 years after PTLD diagnosis)., Conclusion: Treatment of PTLD with rituximab with or without low-dose chemotherapy in combination with reduced immunosuppression, mostly comprising of an mTOR inhibitor-based, calcineurin inhibitor-free regimen, is associated with stable graft function and favorable graft survival in pediatric renal transplant patients., (© 2021 The Authors. Pediatric Transplantation published by Wiley Periodicals LLC.)

Background: CKF is an overwhelming illness, especially in children. Kidney transplantation is considered the definitive management of CKF. It has substantial benefits, including increased patient survival, improved skeletal growth, social adjustment, neuropsychological development, and better quality of life compared to chronic dialysis., Methods: This is a retrospective, clinical, observational study in 13 children ≤16 years old who underwent kidney transplantation at IALCH in KwaZulu-Natal, South Africa, from May 2015 to December 2019., Results: Over 4 years and 7 months, 13 kidney transplants were performed; 7 (53.8%) were males, and 6 (46.2%) were females. Eleven (84.6%) were Black African and 2 (15.4%) Indian children. The mean age ± (SD) of transplantation was 10.1 ± 2.8 years (range 5.8-15.8). Eight (61.5%) children were from a rural setting. The mean ± (SD) duration of follow-up was 29.5 ± 15.9 months. All kidney transplants done were from live related donors; 8 (61.5%) were parents of the recipients. None were pre-emptive transplants. Graft loss occurred in 2 (15.4%) children with 100% patient survival. Two (15.4%) children developed acute rejection., Conclusions: The commissioning of transplant services in KwaZulu-Natal, South Africa, has improved access to this modality of treatment, particularly in our Black African patients. The significant limitations we experienced were a shortage of cadaveric donors and resource limitations with no dedicated transplant unit for pediatric patients together with staffing constraints. Enhancing patient and healthcare personal education will hopefully overcome cultural and religious barriers to organ donation., (© 2021 Wiley Periodicals LLC.)

Donor-specific antibody (DSA) is an independent risk factor for antibody-mediated rejection (ABMR) and graft loss. The C1q assay differentiates complement from non-complement-binding DSA and C1q-binding DSA may lead to poor allograft survival. Our aim was to characterize the type of DSA seen in pediatric kidney transplant recipients and to determine whether complement binding DSA was associated with inferior graft survival.This was a single-center retrospective study of 48 children who were transplanted between 2009 and 2016. DSA were monitored using Luminex single antigen beads. A negative crossmatch was required to proceed with transplantation. The median follow-up time was 4.9 (3.4, 7.9) years. The median age was 12 (5.7, 15.4) years. DSA developed in 27/48 (56.3%), while C1q-binding DSA developed in 17/27 (63%). There were no significant differences between DSA negative, C1q-binding DSA, and C1q negative DSA, with regard to the number of HLA-ABDR (P  =  .09) or HLA-DQ mismatches alone (P  =  .16). For both C1q negative and C1q-binding DSA, DQ was the most common target of the DSA (19/27; 70.4%). C1q-binding DSA was associated with a significantly higher frequency of biopsy proven rejection (76.5%) when compared to C1q negative (10%) and DSA negative (14.3%); P  =  .001. Graft loss was seen in 6 (12.5%), all of whom had C1q-binding DSA (P  =  .004). C1q-binding DSA was most commonly directed to DQ antigens. C1q-binding DSA was associated with increased rejection and graft loss. Monitoring for C1q-binding DSA may risk stratify recipients and guide physician management., (© 2020 Wiley Periodicals LLC.)

Despite correction of underlying solid organ failure by transplantation, pediatric transplant recipients still have increased mortality rates compared to the general pediatric population, in part due to increased cardiovascular risk. In particular, pediatric kidney and non-kidney transplant recipients with chronic kidney disease have significant cardiovascular risk that worsens with declining kidney function. Biomarkers associated with future cardiovascular risk such as casual and ambulatory hypertension, dyslipidemia, vascular stiffness and calcification, and left ventricular hypertrophy can be detected throughout the post-transplant period and in patients with stable kidney function. Among these, hypertension and dyslipidemia are two potentially modifiable cardiovascular risk factors that are highly prevalent in kidney and non-kidney pediatric transplant recipients. Standardized approaches to appropriate BP measurement and lipid monitoring are needed to detect and address these risk factors in a timely fashion. To achieve sustained improvement in cardiovascular health, clinicians should partner with patients and their caregivers to address these and other risk factors with a combined approach that integrates pharmacologic with non-pharmacologic approaches. This review outlines the scope and impact of hypertension and dyslipidemia in pediatric transplant recipients, with a particular focus on pediatric kidney transplantation given the high burden of chronic kidney disease-associated cardiovascular risk. We also review the current published guidelines for monitoring and managing abnormalities in blood pressure and lipids, highlighting the important role of therapeutic lifestyle changes in concert with antihypertensive and lipid-lowering medications., (© 2020 John Wiley Periodicals LLC.)

Background: In children, vitamin D deficiency is common after renal transplantation. Besides promoting bone and muscle development, vitamin D has immunomodulatory effects, which could protect kidney allografts. The purpose of this study was to assess the association between vitamin D status and the occurrence of renal rejection., Methods: We studied a retrospective cohort of 123 children, who were transplanted at a single institution between September 2008 and April 2019. Patients did not receive vitamin D supplementation systematically. In addition, factors influencing vitamin D status were analyzed using univariate and multivariate analyses., Results: Median 25-hydroxy-vitamin D (25-OH-D) concentration was close to reference values at the time of transplantation (30 ng/mL (min-max 5-100)), but rapidly decreased within the first 3 months to 19 ng/mL (min-max 3-91) (P < .001). The overall acute rejection rate was 7%. The clinical rejection rate (5% vs 9%), subclinical rejection (12% vs 36%), and borderline changes (21% vs 28%) were not statistically different during the follow-up between the 3-month 25-OH-D < 20 ng/mL and 3-month 25-OH-D > 20 ng/mL groups. There was a correlation between the 25-OH-D levels and PTH concentration at 3 months (r = -.2491, P = .01), but no correlation between the 3-month 25-OH-D and the season of the year (F = 0.19, P = .90; F = 1.34, P = .27, respectively). Multivariate analyses revealed that age and mGFR at 3 months, were independent predictors of mGFR at 12 months., Conclusion: Our data show that vitamin D deficiency can develop rapidly after transplantation; vitamin D levels at 3 months are not associated with lower mGFR or a higher rejection rate at 1 year in children as opposed to adult recipients., (© 2020 Wiley Periodicals LLC.)