Pediatric Kidney Transplant Recipients Research Articles

Post-transplant de novo non donor-specific HLA antibodies are not associated with poor graft outcome in non-sensitized pediatric recipients of kidney transplantation

While de novo donor-specific HLA antibodies (dnDSAs) have a detrimental impact on kidney graft outcome, the clinical significance of de novo non donor-specific antibodies (dnNDSAs) is more controversial. We retrospectively evaluated for Ab development and characteristics of dnNDSAs serially collected post-transplant sera and, when available, graft biopsy eluates, from 144 non-sensitized, primary pediatric kidney recipients, consecutively transplanted at a single center between 2003 and 2017, using HLA class I and class II single-antigen flow-bead assays (SAB). The results were compared with clinical-pathologic data from HLA antibody negative and HLA dnDSA-positive patients.Forty-five out of 144 patients developed dnNDSAs (31%). Among the dnNDSA-positive patients, 86% displayed one or more class I/II antibodies recognizing antigens included in the CREG/shared epitope groups that also comprise the mismatched donor HLA antigens. Despite potential pathogenicity, as suggested by their occasional presence within the graft, dnNDSAs displayed significantly lower MFI, and limited complement binding and graft homing properties, when compared with dnDSAs. In parallel, the graft survival probability was significantly lower in patients with dnDSA than in those with dnNDSA or without HLA antibodies (p < 0.005). Indeed, the dnNDSA-positive patients remaining dnDSA-negative throughout the posttransplant period did not develop clinical antibody mediated rejection and graft loss, and maintained good graft function at a median follow-up of 9 years. The biological characteristics of dnNDSAs may account for the low graft damaging capability when compared to dnDSAs.

Outcomes of Early Simultaneous Removal of Ureteric Stent With Indwelling Urethral Catheter After Kidney Transplant in Pediatric Recipients: A 10-Year Review

A ureteric stent is routinely placed to minimize urological complications during kidney transplant. However, some complications may occur in association with the ureteric stent, such as urinary tract infections, and the optimal duration for stent placement is unclear. We reviewed the outcomes following early simultaneous removal of the ureteric stent with the urethral catheter in pediatric kidney transplant recipients. We reviewed all kidney transplants from January 2009 to January 2019. The data we collated included demographics, donor and recipient characteristics, and perioperative details, including urological complications, stent-related complications, and kidney graft function. The financial cost of late stent removal was calculated. The early stent removal group was defined as 5 days, and the late removal group was about 4 to 6 weeks. The median follow-up time was 60 months (interquartile range, 31.5-91 months). There were 32 transplants in 31 patients during the study period (early vs late group = 23:9). No urine leak occurred in either group. One patient in the early group developed distal ureteric stenosis, and this condition was managed with interventional balloon dilatation. The median time for stent removal was 6 days in the early group and 39 days in the late group. There were 5 episodes of symptomatic urinary tract infections in 3 patients in the early group and 10 episodes of symptomatic urinary tract infections in 3 patients in the late group. The mean estimated glomerular filtration rate at 12 months was comparable between the 2 groups (84 ± 54 vs 64 ± 21 L/min/1.73 m²; P = .3). The average cost for each early removal was A$772.65 compared with the late group. Early simultaneous removal of the ureteric stent with the urethral catheter in pediatric kidney transplant recipients is feasible, safe, and cost-effective.

BK virus infection and outcome following kidney transplantation in childhood

BK virus associated nephropathy (BKN) is an important cause of kidney allograft failure. In a cohort of paediatric kidney transplant recipients, we aimed to understand the incidence and clinical outcome associated with BKN, as well as identify risk factors for BKN and BK viraemia development. We retrospectively analysed all patients who received a kidney transplant and received follow up care in our centre between 2009–2019. Among 106 patients included in the study (mean follow up 4.5 years), 32/106 (30.2%) patients experienced BK viraemia. The incidence of BKN was 7/106 (6.6%). The median time of BK viraemia development post-transplant was 279.5 days compared to 90.0 days for BKN. Development of BKN was associated with younger age at transplantation (p = 0.013). Development of BK viraemia was associated with negative recipient serology for cytomegalovirus (CMV) at time of transplantation (p = 0.012) and a higher net level of immunosuppression (p = 0.039). There was no difference in graft function at latest follow up between those who experienced BKN and those without BKN. This study demonstrates that BK virus infection is associated with younger age at transplantation, CMV negative recipient serostatus and higher levels of immunosuppression. Judicious monitoring of BK viraemia in paediatric transplant recipients, coupled with timely clinical intervention can result in similar long-term outcomes for BKN patients compared to controls.

Predicting acute rejection in children, adolescents, and young adults with a kidney transplant by assessing barriers to taking medication.

Nonadherence to immunosuppression is common among pediatric, adolescent, and young adult kidney transplant recipients and a leading cause of graft loss. Assessing barriers to medication adherence in clinical practice may identify patients at risk for rejection and provide therapeutic targets. Kidney transplant patients and/or their caregivers were assessed for 14 barriers to medication adherence using the barriers assessment tool. We compared rejection rates between patients with at least one reported adherence barrier to those without reported adherence barriers using a Kaplan-Meier estimator and Cox proportional hazard models to adjust for other mediators of acute rejection at 2 years following barriers assessment. Ninety-eight patients were assessed for barriers to adherence. Over the 2-year observation period, 22 patients developed biopsy-proven acute rejection (BPAR). Kaplan-Meier estimates show that patients with an identified barrier to adherence were more likely to have BPAR (p = 0.02) than patients without an identified barrier in the 24 months following barriers assessment. The median time to rejection for patients who experienced acute rejection was 175.5 days (IQR 63-276 days) from the time of barriers assessment. An identified barrier to adherence remained the only statistically significant predictor of BPAR with Cox modeling (HR 2.6, p = 0.04), after accounting for age, sex, and race. Pediatric and adolescent kidney transplant recipients with identified adherence barriers are at increased risk for acute rejection. Barriers to adherence provide a potentially modifiable therapeutic target that can be assessed in clinic to guide targeted interventions.

Valganciclovir prophylaxis for cytomegalovirus infection in pediatric kidney transplant recipients: a single-center experience.

There are two approaches for treating cytomegalovirus (CMV) infection occurring after kidney transplantation (KTx). One is preemptive therapy in which treatment is started after confirming positive CMV antigenemia using periodic antigenemia assay. The other approach is prophylactic therapy in which oral valganciclovir (VGCV) is started within 10days after KTx and continued for 200days. The Transplantation Society guidelines recommend prophylactic therapy for high-risk (donor's CMV-IgG antibody positive and recipient's negative) pediatric recipients. However, the adequate dose and side effects of VGCV are not clear in children, and there is no sufficient information about prophylaxis for Japanese pediatric recipients. A single-center retrospective analysis was conducted on case series of high-risk pediatric patients who underwent KTx and received oral VGCV prophylaxis at the Department of Pediatric Nephrology, Tokyo Women's Medical University, between August 2018 and March 2019. Data were collected using medical records. The dose of administration was 450mg in all the study patients (n = 5). Reduction or discontinuation was required in four of five patients due to adverse events, which included neutropenia in one patient, anemia in two patients, and neutropenia and digestive symptoms in one patient. Late-onset CMV disease occurred in all patients. No seroconversion was observed during prophylaxis. Our preliminary study suggests that the dosage endorsed by The Transplantation Society may be an overdose for Japanese pediatric recipients. Further studies are required to examine the safety and efficacy of VGCV prophylaxis in Japanese pediatric recipients.

Post-transplant complications, patient, and graft survival in pediatric and adolescent kidney transplant recipients at a tropical tertiary care center across two immunosuppression eras.

We report pediatric PAKT patient and graft outcomes at a large tropical tertiary center spanning two transplant eras. In this retrospective cohort study, all children ≤18years who underwent kidney transplantation at our center between 1991 and 2016 were included. Data pertaining to their baseline characteristics, post-transplant events, and outcome were retrieved from transplant records and compared between transplant eras (1991-2005 and 2006-2016). A total of 139 children (mean age 15.2±2.9years) underwent PAKT during this period. The incidence of UTIs, CMV disease, BKVN, invasive fungal infections, new-onset diabetes after transplant, leucopenia, and recurrent NKD was higher in the 2006-2016 era (P<.001 for all), while 1-year cumulative BPAR was comparable (P=.100). Five-year graft and patient survival in the two eras were 89.9% and 94.2% (P=.365) and 92.1% and 95.3% (P=.739), respectively. Incidence of CMV disease, BKVN, graft loss, and death was lower in the calcineurin withdrawal group. Non-adherence accounted for 36% of graft loss; infections caused 43.7% of deaths. On multivariate Cox proportional hazards analysis, independent predictors for graft loss were UTIs and blood transfusion naïve status and for death were serious infections and glomerular NKD. PAKT in India has excellent long-term graft outcomes, though patient outcomes remain suboptimal owing to a high burden of infections. Current immunosuppression protocols need to be re-examined to balance infection risk, graft, and patient survival.

Low-Dose Antithymocyte Globulin Has No Disadvantages to Standard Higher Dose in Pediatric Kidney Transplant Recipients: Report From the Pediatric Nephrology Research Consortium

IntroductionRabbit antithymocyte globulin (rATG) dosing strategies for induction in pediatric kidney transplantation vary between centers. It is not known whether a lower rATG induction dose provides safe and effective immunosuppression compared with a “standard” higher dose.MethodsWe performed a retrospective multicenter study of all isolated first-time kidney transplant recipients <21 years old who received rATG induction between 1 January 2010 and 31 December 2014 at 9 pediatric centers. An a priori cutoff of a 4.5-mg/kg cumulative rATG dose was used to identify low (≤ 4.5 mg/kg) and standard (> 4.5 mg/kg) exposure groups. Outcomes examined included 12 months posttransplant graft function (estimated glomerular filtration rate [eGFR]); the occurrence of acute rejection, donor-specific antibody (DSA), neutropenia, and viral infection (cytomegalovirus [CMV], Epstein-Barr virus [EBV], and BK virus); and 24-month outcomes of posttransplant lymphoproliferative disorder (PTLD) occurrence and patient and graft survival.ResultsTwo hundred thirty-five patients were included. Baseline features of the low and standard rATG dose groups were similar. By 12 months, the rATG dose group had no significant impact on the occurrence of neutropenia, positive DSA, or viral polymerase chain reaction (PCR). Graft function was similar. Acute rejection rates were similar at 17% (low dose) versus 19% (standard dose) (P = 0.13). By 24 months, graft survival (96.4% vs. 94.6%) and patient survival (100% vs. 99.3%) were similar between the low- and standard-dose groups (P = 0.54 and 0.46), whereas the occurrence of PTLD trended higher in the standard-dose group (0% vs. 2.6%, P = 0.07).ConclusionA low rATG induction dose ≤ 4.5 mg/kg provided safe and effective outcomes in this multicenter low immunologic risk pediatric cohort. Prospective studies are warranted to define the optimal rATG induction dose in pediatric kidney transplantation.

Severe Anemia Caused by Parvovirus B19 Infection in Two Pediatric Kidney Transplantation Recipients

Severe Anemia Caused by Parvovirus B19 Infection in Two Pediatric Kidney Transplantation Recipients

Medication nonadherence and psychosocial issues in pediatric kidney transplant recipients

Medication nonadherence and psychosocial issues in pediatric kidney transplant recipients

CD127 expression in peripheral T cells of pediatric kidney transplant recipients

CD127 expression in peripheral T cells of pediatric kidney transplant recipients

Considerations and controversies of pharmacologic management of the pediatric kidney transplant recipient.

Pediatric kidney transplantation has experienced considerable growth and improvement in patient and allograft outcomes over the past 20years, in part due to advancements in immunosuppressive regimens and management. Despite this progress, care for this unique population can be challenging due to limited pediatric transplant data and trials, intricacies related to differences in children and adolescents compared with their adult counterparts, and limitations to long-term survival facing all solid organ transplant populations. Immunosuppression and infection prevention practices vary from one pediatric transplant center to another and clinical controversies exist surrounding treatment and dosing. This review aims to summarize key aspects of pharmacologic management in this population and present pertinent data that describe the influence of practice to serve as a resource for practitioners caring for this unique specialty patient population. Additionally, this review highlights select controversies that exist within pediatric kidney transplantation.

An Overview of the Long-term Follow-up of the Adult Post-kidney Transplant Recipients in Sudan: A Single-Center Experience.

Kidney transplant remains the definitive treatment for patients with end-stage renal disease. A retrospective cohort was conducted in Dr. Selma Center for Kidney Diseases (DSCKD) to determine the pattern of follow-up and outcomes of adult kidney transplant recipients (KTRs) on long-term follow-up. Patients presented for follow-up during the period from January to June 2018 were studied regarding their demographic features, kidney transplant surgery, immunosuppressive therapy, graft function, and post-transplant complications. Data analysis was done using the Statistical Package for the Social Sciences version 16.0. During the study period, a total of 941 adult and pediatric KTR presented to DSCKD for follow-up. Only 792 KTRs were included in the study; those were adults, with their first kidney transplant, completed one year post-transplant, and agreed for enrollment. The mean age of the studied population was 47 ± 4.3 years. The majority were males, 74.2%. The median duration of follow-up was 7.4 years (interquartile range 3-11). Most transplants were through living-related donations, 78.8%. The combination of prednisolone, tacrolimus, and azathioprine remains the most common immunosuppressive regimen prescribed; delivered to 47.5% of recipients. Post-transplant complications were predominantly recurrent infections, diabetes mellitus, and hyperlipidemia seen in 54.5%, 42.4%, and 24.7% of recipients, respectively. On cross-comparisons living unrelated donor transplant recipients were found to have increased post-transplant complications, with a reduced kidney graft function at the end of the 1st year and throughout follow-up, when compared to living related donor transplant recipients. A prospective multi-center study with long-term follow-up remains essential for further evaluation of the long-term outcomes of the KTR in Sudan.

CD62L Percentage in Peripheral T Cells of Kidney Transplant Recipients Children

Backgrounds: Recent advances in post Kidney Transplantation (KT) care, have led to a dramatic improvement in short-term outcomes in order to achieve transplantation tolerance; including the ideal tool for clinical monitoring & new therapeutic line. This study was undertaken to analyze the CD62L in Kidney Transplant Recipients (KTRs) and to investigate its efficacy as a marker of good graft survival. Methods: Fifty pediatric KTRs and 12 healthy controls were included in the study, the frequency of T cell activation markers; CD62L was measured with flow cytometry after renal transplantation. Clinical, laboratory, immunosuppressive therapy data and graft function of transplant recipients were collected and correlated with their CD62L peripheral blood percentage. Results: The circulating CD62L% was significantly more in transplant recipients than controls (44.74% ± 17.45% vs. 33.36% ± 11.54%, p = 0.02). CD 62L% was more frequent in recipients of living related donors (p = 0.05), positively correlated with donor age (p = 0.04, r = -0.29*) and CD 4% (p = 0.000, r = 0.615). CD26L% did not show significant association with acute rejection or chronic rejection (p = 0.432, p = 0.91 respectively) or with graft function (serum creatinine or eGFR, p = 0.086, p = 0.988 respectively) or immunosuppressive medications. Conclusion: Peripheral CD62L% is increased after KT than healthy controls, however, it cannot reflect either clinical (serum creatinine and eGFR) or pathological renal graft injury. CD62L surface marker needs more analysis for its potential diagnostic and therapeutic implications as a Treg cell activation marker.

Kidney re-transplantation in a child across the barrier of persisting angiotensin II type I receptor antibodies

BackgroundApproximately 20% of antibody-mediated rejection (ABMR) episodes in the absence of donor-specific antibodies against human leucocyte antigens (HLA-DSA) in pediatric and adult kidney transplant recipients are associated with, and presumably caused by, antibodies against the angiotensin type 1 receptor (AT1R-Ab). While the role of AT1R-Ab for ABMR and graft failure is increasingly recognized, there is little information available on the management of these patients for re-transplantation over the barrier of persisting AT1R-Ab.CaseWe report on a male patient with kidney failure in infancy due to obstructive uropathy who had lost his first kidney transplant due to AT1R-Ab-mediated chronic ABMR. Because this antibody persisted during 4 years of hemodialysis, for the 2nd kidney transplantation (living-related transplantation from his mother), he underwent a desensitization regimen consisting of 15 plasmapheresis sessions, infusions of intravenous immunoglobulin G and thymoglobulin, as well as pharmacological blockade of the Angiotensin II (AT II) pathway by candesartan. This intense desensitization regimen transiently decreased elevated AT1R-Ab titers, resulting in stable short-term kidney allograft function. The subsequent clinical course, however, was complicated by acute cellular rejection and chronic ABMR due to persistent AT1R-Ab and de novo HLA-DSA, which shortened allograft survival to a period of only 4 years.ConclusionThis case highlights the difficulty of persistently decreasing elevated AT1R-Ab titers by a desensitization regimen for re-transplantation and the detrimental effect of the interplay between AT1R-Ab and HLA-DSA on kidney transplant survival.

Age and sex determine conversion from immediate-release to extended-release tacrolimus in a multi-center cohort of Canadian pediatric renal transplant recipients.

ER-Tac, taken once per day, is associated with improved adherence. This study examined the potential patient and clinical factors that influence clinicians to convert pediatric patients from immediate-release to ER-Tac. This prospective multi-center observational study followed Canadian pediatric kidney transplant recipients up to 5years post-transplant. Cox Proportional Hazards Regression was used to examine the influence of factors on conversion to ER-Tac. Sixty-six participants were included in this analysis. For every additional year of age at the time of transplant, the likelihood of conversion was more than doubled (HR 2.54, CI 1.83, 3.54, P<0.001). The impact of age reduced by three percent for every month after transplant (HR 0.97, CI 0.95, 0.98, P<0.001). Girls were more likely to be converted than boys (HR 3.78, CI 1.35, 10.6, P 0.01). Adherence measures (MAM-MM and tacrolimus trough variability), individual barriers to adherence, renal function, HLA mismatch, and rejection were not significant predictors of conversion in the final regression model. ER-Tac was preferentially prescribed to older age and female patients. Female sex and adolescence are both associated with worse graft outcomes, but we found no link between individualized markers of adherence/graft risk and conversion. Clinicians appeared to be using demographic features to distinguish patients at perceived higher risk and converted accordingly, without a case-by-case evaluation of who is more susceptible to poor outcomes.

Glucose tolerance in a cohort of Egyptian children after kidney transplantation

BackgroundPost- transplantation diabetes mellitus (PTDM) in children is a serious metabolic complication that can endanger both graft and patient survival. These complications can be partially reduced by early diagnosis & prompt treatment of impaired glucose tolerance. The aim of this study was to assess glucose tolerance & insulin resistance among a cohort of kidney transplanted children. MethodsThirty consecutive pediatric kidney transplant recipients were subjected to basal evaluation of plasma glucose and insulin then underwent oral glucose tolerance test (OGTT). ResultsAbnormal glucose metabolism was detected in 7 (23.3%) patients; 3 (10%) patients with PTDM; 3 (10%) patients with impaired fasting glucose (IFG) and 1 (3.3%) patient with IFG and impaired glucose tolerance (IGT). Four (13.3%) patients had high Homeostatic model assessment of insulin resistance (HOMA-IR). Patients with abnormal glucose metabolism had significantly higher tacrolimus trough levels and higher maintainence steroid doses (p values = 0.003,0.026). Significant positive correlation existed between pre-transplantation glucose level and post-transplantation fasting glucose (p = 0.001, r = 0.69), glucose at 120 min (p = 0.018, r = 0.429) and HOMA-IR (p = 0.008, r = 0.47). ConclusionAbnormalities in glucose metabolism (IFG, IGT &PTDM) are frequent in Egyptian pediatric kidney transplant recipients. OGTT is the gold standard for assessment of abnormalities in glucose metabolism.

Complications of surgical mesh patches after kidney transplantation in children-A case series.

Abdominal compartment syndrome after kidney transplantation in pediatric recipients is a recognized complication relating to size discrepancy requiring abdominal wall closure over a large adult allograft. In order to circumvent this problem, our center implemented use of a surgical mesh, Surgisis® (Cook Surgical, Bloomington, IN), for abdominal wall closure in very small children to increase the surface covering over the organ and prevent compression. In this article, we report on the complications encountered following the use of these mesh patches. A retrospective case review was conducted of all pediatric kidney transplants from September 2006 to December 2018 and divided into abdominal wall closure with and without implantation of Surgisis® mesh patch. Review of clinical notes was performed to identify information with respect to clinical course and post-operative outcomes. A surgical mesh patch was used in 7 pediatric recipients, of which 5 (71%) presented with post-operative complications. Three recipients were found to have bowel obstruction related to the surgical patch, necessitating bowel resection in one child. In addition, three children developed large serous fluid collections between the subcutaneous layers and the surgical mesh, requiring surgical drainage in two. In view of these findings, we recommend close surveillance for potential complications in this cohort. Future research is needed to explore the safety of different approaches to achieve abdominal wall closure in this group.

Dapsone-induced methemoglobinemia in pediatrics post-renal transplant.

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.

Tacrolimus exposure and intra-patient variability in paediatric and young adult kidney transplant recipients: one size does not fit all.

Paediatric practice recommendations on the use of tacrolimus following kidney transplantation are largely based on the experience from adult solid organ recipients. It has been reported that adequate tacrolimus exposure in adults can impact patient outcomes. As shown in the SYMPHONY trial, adult de novo kidney transplant patients with a target tacrolimus pre-dose concentration (TAC C0 ) of 3-7ng/ml had a higher glomerular filtration rate and a lower incidence of acute rejection oneyear following transplantation compared to those treated with cyclosporine A or sirolimus.

Prognostic Factors on Graft Function in Pediatric Kidney Recipients

BackgroundGraft survival in pediatric kidney transplant recipients has increased in the last decades. Determining prognostic factors for graft function over time allows the identification of patients at risk for graft loss and could lead to improvement of current guidelines. MethodsData were collected among pediatric kidney transplant recipients in a single center during the first 5 years after transplantation. Mixed model analysis was used to indicate possible prognostic factors for the loss of graft function. ResultsA total of 100 pediatric kidney transplant recipients were analyzed. Negative prognostics of graft function are higher donor age and higher recipient age, presence of obstructive uropathology, re-transplant, and occurrence of BK viremia. The negative influence on graft function of both donor age and presence of obstructive uropathology increased over time. In this study, the factors that did not influence graft function over time were the number of HLA mismatches, pre-transplant dialysis, intra-abdominal graft placement, ischemia time, occurrence of acute rejection, presence of lower urinary tract dysfunction, occurrence of urinary tract infections, and infections with cytomegalovirus and Epstein-Barr virus. ConclusionsThis study showed that a higher donor age and higher recipient age, presence of obstructive uropathology, a re-transplant, and the occurrence of BK viremia were negative prognostic factors of graft function over time, in the first 5 years after transplant. Graft function was comparable between steroid-sparing regimens (preferable in low-risk patients) and regimens including steroids (for special reasons).