Pediatric Renal Allograft Research Articles

Kidney Retransplantation in Children.

Pediatric kidney transplant recipients will likely require a retransplant in their lifetime. Although the significant advances in clinical management and newer immunosuppressive agents have had a significant effect to improve short-term allograft function, it is apparent that long-term allograft function remains suboptimal. Therefore, it is likely that most pediatric renal allograft recipients will require 1 or more retransplants during their lifetime. In the West, an increasing number of patients on the deceased donor wait list are awaiting a retransplant; in the US, 15% of current annual transplants are retransplants. Unfortunately, the use of a second or subsequent grafts in pediatric recipients has inferior long-term graft survival rates compared with initial grafts, with decreasing rates with each subsequent graft. Multiple issues influence the outcome of retransplant, with the most significant being the cause of the prior transplant failure. Nonadherenceassociated graft loss poses unresolved ethical issues that may affect a patient's access to retransplant. Graft nephrectomy prior to retransplant may benefit selected patients, but the effect of an in situ failed graft on the development of panel reactive antibodies remains to be definitively determined. It is important that these and other factors discussed in this presentation be taken into consideration during the counseling of families on the optimal approach for their child who requires a retransplant.

Practice patterns and influence of allograft nephrectomy in pediatric kidney re-transplantation: A pediatric nephrology research consortium study.

There are no guidelines regarding management of failed pediatric renal transplants. 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. 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 3months (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). 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.

Tacrolimus Bayesian Dose Adjustment in Pediatric Renal Transplant Recipients.

Immunosuppressant Bayesian Dose Adjustment (ISBA) is an online expert system that estimates the area under the curve (AUC) of immunosuppressive drugs through pharmacokinetic modelling and Bayesian estimation to propose dose adjustments to reach predefined exposure targets. The ISBA database was retrospectively analyzed to describe tacrolimus pharmacokinetics and exposure, evaluate the efficiency of ISBA dose recommendations, and propose tacrolimus AUC0-12h target ranges for pediatric renal allograft recipients treated with immediate release tacrolimus. The database included 1935 tacrolimus dose adjustment requests from 419 patients <19 years old who were treated with immediate-release tacrolimus and followed in 21 French hospitals. The tacrolimus exposure evolution with patient age and posttransplantation time, the correlation between trough tacrolimus concentration (C0) and AUC0-12h at different periods posttransplantation, and the efficiency of dose recommendations to avoid underexposure and overexposure and to decrease between-patient AUC variability were investigated. Tacrolimus AUC showed large between-patient variability (CV% = 40%) but moderate within-patient variability (median = 24.3% over a 3-month period). Dose-standardized exposure but not the AUC/C0 ratio significantly decreased with time posttransplantation and patient age. We derived AUC0-12h ranges from the consensual C0 ranges using linear regression equations. When the ISBA recommended dose was applied, the AUC distribution was narrower and a significantly higher proportion was within the targets (P < 0.0001). ISBA efficiently reduced tacrolimus underexposure and overexposure. The AUC0-12h target ranges for pediatric patients derived from the database were similar to those previously reported for adults. Estimating the AUC/C0 ratio could help determine personalized C0 targets.

Early surveillance biopsy utilization and management of pediatric renal allograft acute T cell-mediated rejection in Canadian centers: Observations from the PROBE multicenter cohort study.

Early TCMR surveillance with protocol kidney biopsy is used differentially among pediatric kidney transplant centers. Little has been reported about actual center-based differences, and this variability may influence TCMR ascertainment, treatment, and monitoring more broadly. Data from the PROBE multicenter study were used to identify patients from centers conducting ESB or LSIB. ESB was defined as >50% of patients having at least 1 surveillance biopsy in the first 9months. Patients were compared for number of biopsies, rejection episodes, treatment, and follow-up monitoring. A total of 261 biopsies were performed on 97 patients over 1-2years of follow-up. A total of 228 (87%) of biopsies were performed in ESB centers. Compared to LSIB centers, ESB centers had 7-fold more episodes of TCMR diagnosed on any biopsy [0.8±1.2 vs 0.1±0.4; P<.001] and a 3-fold higher rate from indication biopsies [0.3±0.9 vs 0.1±0.3; P=.04]. The proportion of rejection treatment varied based on severity: Banff borderline i1t1 (40%);>i1t1 and<Banff 1A (86%); and≥Banff 1A (100%). Biopsies for follow-up were performed after treatment in 80% of cases (n=28) of rejection almost exclusively at ESB centers, with 17 (61%) showing persistence of TCMR (≥i1t1). Practice variation exists across Canadian pediatric renal transplant centers with ESB centers identifying more episodes of rejection. Additionally, treatment of Banff borderline is not universal and varies with severity regardless of center type. Lastly, follow-up biopsies are performed inconsistently and invariably show persistence of rejection.

Immunohistochemical and Molecular Characterization of Immune Cells in Pediatric Renal Allografts: Mononuclear Phagocytes Correlate with Rejection, Re-Transplantation, Graft Function, and Fibrosis

Immunohistochemical and Molecular Characterization of Immune Cells in Pediatric Renal Allografts: Mononuclear Phagocytes Correlate with Rejection, Re-Transplantation, Graft Function, and Fibrosis

Human leukocyte antigen eplet mismatches and long‐term clinical outcomes in pediatric renal transplantation: A pragmatic, registry‐based study

HLA epitope-based matching offers the potential to improve immunological risk prediction and management in children receiving renal allografts; however, studies demonstrating the association between systems for defining epitope mismatches and clinical end-points are lacking in this population. We conducted a pragmatic, retrospective, registry-based study of pediatric recipients of primary renal allografts in Victoria, Australia between 1990 and 2014 to determine the association between HLA EpMM and clinical outcomes including graft failure, re-transplantation and dnDSA formation. A total of 196 patients were included in the analysis with a median age of 11years. Median follow-up period was 15years during which time 108 (55%) primary grafts failed and 72 patients were re-transplanted. HLA class I but not class II EpMM was a significant predictor of graft failure on univariate analysis but not in adjusted models. EpMM was associated with reduced likelihood of re-transplantation in univariate but not adjusted analysis. Within the limitations of the study, class-specific EpMM was a strong predictor of dnDSA formation. Associations were stronger when considering only the subset of antibody-verified EpMM. Associations between HLA EpMM and clinical outcomes in pediatric renal allograft recipients seen on univariate analysis were attenuated following adjustment for confounders. These findings are inconclusive but suggest that HLA EpMM may provide one tool for assessing long-term risk in this population while highlighting the need for further clinical studies.

Low-Dose Aspirin Reduces the Rate of Renal Allograft Thrombosis in Pediatric Renal Transplant Recipients.

Renal allograft thrombosis is an important cause of early renal allograft loss. A previous study from our unit showed thrombosis rates in patients who received heparin that were similar to those who did not receive any thromboprophylaxis. This study evaluated the impact of aspirin prophylaxis on renal allograft thrombosis rates in pediatric renal transplant recipients. We conducted a retrospective study of 456 consecutive pediatric allografts from deceased and living related donors over age 22 years in a single center. Routine perioperative heparin was introduced in 1994 and was subsequently changed to aspirin prophylaxis in 2000. Group 1 comprised 126 patients who did not receive any thromboprophylaxis, group 2 comprised 128 patients who received heparin, and group 3 comprised 202 patients who received aspirin therapy. Variables associated with increased risk of renal allograft loss were examined using multivariable logistic regression. Thrombosis occurred in 11% (14/126) of grafts in group 1, 9% (11/128) of grafts in group 2, and 1% (2/202) of grafts in group 3 (odds ratio for aspirin group = 0.38, 95% confidence interval, 0.22-0.64; P = .02). In patients who received aspirin (group 3), there was only one renal allograft loss secondary to hemorrhage, and no grafts were lost in patients younger than 5 years of age. After our center introduced a change from heparin to aspirin prophylaxis, the thrombosis rate in pediatric renal allografts fell from 9% to 1%. Although there are a number of possible confounding variables, the introduction of aspirin has led to a reduced rate of renal allograft thrombosis.

Cytomegalovirus and Epstein-Barr virus infections among pediatric kidney transplant recipients at a center using universal Valganciclovir Prophylaxis.

CMV is associated with adverse effects in renal transplant recipients. The objective of this study was to characterize the incidence and timing of CMV and EBV infections in relation to valGCV prophylaxis in a pediatric renal transplant cohort. Retrospective cohort of pediatric renal transplant patients given universal valGCV prophylaxis and universal viral surveillance was evaluated. Demographics, prophylaxis, acute rejection, and CMV and EBV infections were abstracted. A total of 92 pediatric renal allograft recipients, 2008-2013, were included. One or more viral infections developed in 77/92 (83.7%) of the patients. EBV was the most common in 62/92 (67%) patients, irrespective of valGCV (82% of episodes occurring on valGCV). CMV DNAemia occurred in 30/92 (33%) patients, 14 episodes (47%) occurring on valGCV. Incidence of breakthrough CMV on prophylaxis was 15% and was associated with persistent DNAemia (OR 7.8, CI:1.6-32.9, P<0.02). CMV tissue-invasive disease was not seen. CMV syndrome occurred in 10% of the cohort, only in CMV D+ patients, and only one symptomatic breakthrough infection required treatment. Out of 92, 21 (23%) had simultaneous co-infections with 2-3 viruses. Viral infections in pediatric renal transplant recipients receiving universal valGCV prophylaxis were common. EBV infections were not reduced by valGCV prophylaxis, and nearly half of CMV infections occurred on valGCV. Symptomatic CMV infection while on prophylaxis was rare. valGCV prophylaxis may prevent symptomatic CMV infection but not EBV infection, and frequent CMV surveillance in pediatric renal transplant recipients on prophylaxis may not be necessary.

Renal allograft survival rates in kidneys initially declined for paediatric transplantation

BackgroundThe outcome of organs which have been declined for paediatric recipients is not known. This study aimed to determine the outcome of kidneys initially declined for paediatric recipients and establish renal allograft survival in kidneys that were eventually transplanted.MethodsData were obtained from the UK Transplant Registry for all donation after brain death (DBD) kidneys offered and declined to paediatric recipients (< 18 years) in the UK from 2009 to 2014.ResultsEighty-two percent (503/615) of kidneys initially declined for paediatric transplantation were eventually transplanted, 7% (46/615) of kidneys went to paediatric recipients and 62% (384/615) of kidneys went to adult (kidney only) recipients. The remainder were used for multiple organ transplants. In the 46 kidneys that went to paediatric recipients, 1 and 3-year renal allograft survivals were 89% (95% CI 75.8–95.3%) and 82% (95% CI 67.1–90.6%), respectively. In the 384 kidneys given to adult kidney-only recipients, 1 and 3-year renal allograft survivals were 96% (95% CI 93.5–97.6%) and 94% (95% CI 90.7–96.1%), respectively. Eighty-four percent of the 204 children who initially had an offer declined on their behalf were eventually transplanted and have a functioning graft at a median 3-year follow-up.ConclusionsThis study reports acceptable short-term renal allograft survival in kidneys that were initially declined for paediatric recipients and subsequently transplanted. Evidence-based guidelines are required to ensure that the most appropriate kidneys are selected for paediatric recipients.

Prevalence, morbidity, and therapy of hepatitis E virus infection in pediatric renal allograft recipients.

Hepatitis E virus (HEV) infection in immunocompromised patients such as solid organ transplant recipients may bear a high risk of becoming a chronic infection with progression to liver cirrhosis. So far, data on HEV infection in pediatric renal transplant recipients are limited. This single-center cohort study investigated period prevalence, morbidity, and treatment of HEV infection in 90 pediatric renal allograft recipients aged 9.9 ± 5.6years at transplantation (58.9% males). HEV serology was determined by enzyme-linked immunosorbent assay and immunoblot, HEV replication by quantitative nucleic acid testing. Twelve of 90 (13.3%) patients were HEV seropositive, and 4/90 (4.4%) recipients showed active HEV replication (103-108 copies/mL, corresponding to 0.5 × 103 and 0.5 × 108 WHO IU/mL) in serum and stool. In all patients with HEV replication, genotype 3 was identified by partial sequencing of HEV ORF1 and ORF2 and phylogenetic analysis. All patients with HEV replication developed chronic infection associated with moderately elevated liver enzymes. HEV replication was unresponsive to reduction of immunosuppression, whereas ribavirin monotherapy (mean dosage 9.7 ± 3.6mg/kg per day over 85 ± 11days) was associated with sustained viral clearance and normalization of liver enzymes in all patients. Ribavirin therapy was associated with reversible, hyporegenerative anemia. Given an HEV seroprevalence of 13.3% in pediatric renal transplant recipients and an HEV viremia of 4.4%, HEV infection should be considered in patients with otherwise unexplained elevation of liver enzymes. HEV infection does not necessarily respond to reduction of immunosuppressive therapy, but can be effectively and safely treated with ribavirin.

Vaccination titres pre- and post-transplant in paediatric renal transplant recipients and the impact of immunosuppressive therapy.

Avoidance of vaccine-preventable infections in paediatric renal allograft recipients is of utmost importance. However, the development and maintenance of protective vaccination titres may be impaired in this patient population owing to their need for immunosuppressive medication. In the framework of the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN), we therefore performed a multi-centre, multi-national study and analysed vaccination titres pre- and post-transplant in 155 patients with serial titre measurements in comparison with published data in healthy children. The percentage of patients with positive vaccination titres before renal transplantation (RTx) was low, especially for diphtheria (38.5%, control 75%) and pertussis (21.3%, control 96.3%). As few as 58.1% of patients had a hepatitis B antibody (HBsAb) titre >100 IU/L before RTx. 38.1% of patients showed a vaccination titre loss post-transplant. Patients with an HBsAb titre between 10 and 100 IU/L before RTx experienced a significantly (p < 0.05) more frequent hepatitis B vaccination titre loss post-transplant than patients with an HBsAb titre >100 IU/L. The revaccination rate post-transplant was low and revaccination failed to induce positive titres in a considerable number of patients (27.3 to 83.3%). Treatment with rituximab was associated with a significantly increased risk of a vaccination titre loss post-transplant (odds ratio 4.26, p = 0.033). These data show a low percentage of patients with positive vaccination titres pre-transplant, a low revaccination rate post-transplant with limited antibody response, and a high rate of vaccination titre losses.

Posttransplant lymphoproliferative disorder: Experience from a pediatric nephrology unit in North India

Posttransplant lymphoproliferative disorder (PTLD) is reported in 1%–3% among pediatric renal allograft recipients. We report the experience of PTLD among pediatric renal allograft recipients at a pediatric nephrology center in North India. Four cases of PTLD were identified from among records of 95 pediatric renal allograft recipients over a period of 21 years. Constitutional and localizing symptoms were present in three patients each. The diagnosis was suggested on positron emission tomography in three patients and confirmed by histopathology in all. Sites affected included tonsils, cervical lymph nodes, duodenum, and para-aortic lymph nodes in one patient each. The lymphocytic infiltrate was polymorphic in three patients and monomorphic in one. Immunostaining suggested B-cell origin in all patients. There was evidence of Epstein–Barr virus infection in only one patient. The patients were successfully managed with reduction of immunosuppression (in all), rituximab (in 3), and excision of affected tissue (in 1). Over a follow-up period of 30–88 months, there were no episodes of disease recurrence or allograft rejection, and renal function was preserved.

Expression of Mitochondrial-Encoded Genes in Blood Differentiate Acute Renal Allograft Rejection.

Despite potent immunosuppression, clinical and biopsy confirmed acute renal allograft rejection (AR) still occurs in 10–15% of recipients, ~30% of patients demonstrate subclinical rejection on biopsy, and ~50% of them can show molecular inflammation, all which increase the risk of chronic dysfunction and worsened allograft outcomes. Mitochondria represent intracellular endogenous triggers of inflammation, which can regulate immune cell differentiation, and expansion and cause antigen-independent graft injury, potentially enhancing the development of acute rejection. In the present study, we investigated the role of mitochondrial DNA encoded gene expression in biopsy matched peripheral blood (PB) samples from kidney transplant recipients. Quantitative PCR was performed in 155 PB samples from 115 unique pediatric (<21 years) and adult (>21 years) renal allograft recipients at the point of AR (n = 61) and absence of rejection (n = 94) for the expression of 11 mitochondrial DNA encoded genes. We observed increased expression of all genes in adult recipients compared to pediatric recipients; separate analyses in both cohorts demonstrated increased expression during rejection, which also differentiated borderline rejection and showed an increasing pattern in serially collected samples (0–3 months prior to and post rejection). Our results provide new insights on the role of mitochondria during rejection and potentially indicate mitochondria as targets for novel immunosuppression.

Incomplete vaccination coverage in European children with end-stage kidney disease prior to renal transplantation.

Because infections constitute a major cause of morbidity and mortality in paediatric renal allograft recipients, avoidance of preventable systemic infections by vaccination before transplantation is of utmost importance. However, data on the completeness of vaccinations and factors associated with incomplete vaccination coverage are scarce. Within the framework of the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN), we therefore performed a multi-centre, multi-national, retrospective study investigating the vaccination coverage before transplantation of 254 European children with end-stage renal disease (mean age 10.0±5.6years). Only 22 out of 254 patients (8.7%) presented complete vaccination coverage. In particular, the respective vaccination coverage against human papillomavirus (27.3%), pneumococci (42.0%), and meningococci (47.9%) was low. Patients with complete pneumococcal vaccination coverage had numerically less lower respiratory tract infections during the first 3years post-transplant than children without vaccination or with an incomplete status (16.4% vs 27.7%, p=0.081). Vaccine-preventable diseases post-transplant were 4.0 times more frequently in unvaccinated than in vaccinated patients. Factors associated with an incomplete vaccination coverage were non-Caucasian ethnicity (OR 9.21, p=0.004), chronic dialysis treatment before transplantation (OR 6.18, p=0.001), and older age at transplantation (OR 1.33, p<0.001). The vaccination coverage in paediatric kidney transplant candidates is incomplete. Paediatric nephrologists, together with primary-care staff and patients' families, should therefore make every effort to improve vaccination rates before kidney transplantation.

Tacrolimus dose requirements in paediatric renal allograft recipients are characterized by a biphasic course determined by age and bone maturation.

Despite longstanding recognition of significant age-dependent differences in drug disposition during childhood, the exact course and the underlying mechanisms are not known. Our aim was to determine the course and determinants of individual relative dose requirements, during long-term follow-up in children on tacrolimus. This was a cohort study in a tertiary hospital with standardized annual pharmacokinetic (PK) follow-up (AUC0-12hr ) in recipients of a renal allograft (≤19 years), between 1998 and 2015. In addition, the presence of relevant pharmacogenetic variants was determined. The evolution of dose-corrected exposure was evaluated using mixed models. A total of 184 PK visits by 43 children were included in the study (median age: 14.6). AUC0-12h corrected for dose per kg demonstrated a biphasic course: annual increase 4.4% (CI: 0.3-8.7%) until ±14 years of age, followed by 13.4% increase (CI 8.7-18.3%). Moreover, exposure corrected for dose per m2 proved stable until 14 years (+0.8% annually; CI: -3.0 to +4.8%), followed by a steep increase ≥14 years (+11%; CI: 7.0-16.0%). Analysis according to bone maturation instead of age demonstrated a similar course with a distinct divergence at TW2: 800 (P=0.01). Genetic variation in CYP3A4, CYP3A5, and CYP3A7 was associated with altered dose requirements, independent of age. Children exhibit a biphasic course in tacrolimus disposition characterized by a high and stable drug clearance until a specific phase in pubertal development (TW2: 800 at age: ±14 years), followed by an important decline in relative dose requirements thereafter. Pharmacogenetic variation demonstrated an age/puberty independent effect. We suggest a critical reappraisal of current paediatric dosing algorithms for tacrolimus and drugs with a similar disposition.

Surveillance biopsies after paediatric kidney transplantation: A review

Kidney transplantation is the most effective means of treating children with end-stage kidney disease, and yet, there continues to be a limited "life span" of transplanted kidneys in paediatric recipients. Early graft monitoring, using the surveillance biopsy, has the potential to extend renal allograft survival in paediatric recipients. The surveillance biopsy provides important and timely information about acute and chronic graft pathology, particularly SCR and calcineurin inhibitor-induced nephrotoxicity, which can subsequently guide management decisions and improve long-term graft survival. The ostensible value of the surveillance biopsy is furthered by the limitations of conventional renal functional studies. However, there is still much debate surrounding the surveillance biopsy in paediatric recipients, particularly in regard to its overall utility, safety and timing. This review discusses the current literature regarding the utility, safety, and potential predictive value of surveillance biopsies for guiding post-transplant management in paediatric renal allograft recipients, as well as the viability of other potentially newer non-invasive strategies for renal allograft monitoring.

Kidney retransplantation in children following rejection and recurrent disease.

Retransplantation accounts for approximately 15% of the annual transplants performed in the USA, and in the recent International Collaborative Transplant Study report on pediatric patients 15.2% of the 9209 patients included in the report were retransplant recipients. Although the significant advances in clinical management and newer immunosuppressive agents have had a significant impact on improving short-term allograft function, it is apparent that long-term allograft function remains suboptimal. Therefore, it is likely that the majority of pediatric renal allograft recipients will require one or more retransplants during their lifetime. Unfortunately, a second or subsequent graft in pediatric recipients has inferior long-term graft survival rates compared to initial grafts, with decreasing rates with each subsequent graft. Multiple issues influence the outcome of retransplantation, with the most significant being the cause of the prior transplant failure. Non-adherence-associated graft loss poses unresolved ethical issues that may impact access to retransplantation. Graft nephrectomy prior to retransplantation may benefit selected patients, but the impact of an in situ failed graft on the development of panel-reactive antibodies remains to be definitively determined. It is important that these and other factors discussed in this review be taken into consideration during the counseling of families on the optimal approach for their child who requires a retransplant.

Steroid Avoidance or Withdrawal Regimens in Paediatric Kidney Transplantation: A Meta-Analysis of Randomised Controlled Trials.

BackgroundWe combined the outcomes of all randomised controlled trials to investigate the safety and efficacy of steroid avoidance or withdrawal (SAW) regimens in paediatric kidney transplantation compared with steroid-based (SB) regimens.MethodsA systematic literature search of PubMed, Embase, Cochrane Library, the trials registry and BIOSIS previews was performed. A change in the height standardised Z-score from baseline (ΔHSDS) and acute rejection were the primary endpoints.ResultsEight reports from 5 randomised controlled trials were included, with a total of 528 patients. Sufficient evidence of a significant increase in the ΔHSDS was observed in the SAW group (mean difference (MD) = 0.38, 95% confidence interval (CI) 0.07–0.68, P = 0.01), particularly within the first year post-withdrawal (MD = 0.22, 95% CI 0.10–0.35, P = 0.0003) and in the prepubertal recipients (MD = 0.60, 95% CI 0.21–0.98, P = 0.002). There was no significant difference in the risk of acute rejection between the groups (relative risk = 1.04, 95% CI 0.80–1.36, P = 0.77).ConclusionsThe SAW regimen is justified in select paediatric renal allograft recipients because it provides significant benefits in post-transplant growth within the first year post-withdrawal with minimal effects on the risk of acute rejection, graft function, and graft and patient survival within 3 years post-withdrawal. These select paediatric recipients should have the following characteristics: prepubertal; Caucasian; with primary disease not related to immunological factors; de novo kidney transplant recipient; with low panel reactive antibody.

Anti-HLA antibodies in pediatric renal transplant recipients – Analysis of potential triggers

Aim HLA antigen sensitization poses a challenge both before and after renal transplantation (KTx). Its etiology and clinical importance in pediatric transplant recipients is not well understood. The aim of the study was to examine potential causes of HLA antibody formation in children pre- and post KTx. Methods A retrospective chart review of pediatric renal allograft recipients ages 1–18 years and transplanted between January 2009 and December 2014 was performed. Data extracted included potential sensitizing events (transfusion, rejection, infection, vaccination) and anti-HLA antibody (Ab) status. Ab were detected by flow cytometry-based single antigen bead assays. A mean fluorescence intensity (MFI) > 1000 was considered positive. Other events such as delayed graft function were not included in the analysis. Results Of a total of 20 transplanted patients (8 females), 5 received a living-related and 15 a de-ceased donor graft. The median age at KTx was 9.2 years. Eleven of the 20 patients (55%) had detectable HLA Ab during a median follow-up of 3.1 years. Two patients had de-novo donor-specific antibodies (DSA) and two had self-antibodies. Major possible causes of HLA sensitization were blood and platelet transfusions, infections and vaccinations (Table). Mono-specific HLA Ab were identified in 5, multi-specific Ab in 3, and mono- and multi-specific Ab (at discrete occasions) in 3 children. A possible sensitizing immunological trigger was noted in 1 patient with mono-specific, 6 patients with multi-specific, and 1 patient with sequential detection of mono- and multi-specific HLA Ab. Conclusion Our results demonstrate that transfusions, infections and/or immunizations may sensitize pediatric graft recipients leading to mono- or multi-specific HLA Ab. Their clinical significance, specifically concerning antibody-mediated rejection and graft outcome, remains to be established. Download : Download full-size image

Racial and ethnic disparities in pediatric renal allograft survival in the United States

This study was undertaken to describe the association of patient race/ethnicity and renal allograft survival among the national cohort of pediatric renal allograft recipients. Additionally, we determined whether racial and ethnic differences in graft survival exist among individuals living in low or high poverty neighborhoods and those with private or public insurance. Among 6,216 incident, pediatric End Stage Renal Disease patients in the United States Renal Data System (kidney transplant from 2000 through September, 2011) 14.4% experienced graft failure, with a median follow-up time of 4.5 years. After controlling for multiple covariates, black race, but not Hispanic ethnicity, was significantly associated with a higher rate of graft failure for both deceased and living donor transplant recipients. Disparities were particularly stark by 5 years post-transplant, when black living donor transplant recipients experienced only 63.0% graft survival compared with 82.8% and 80.8% for Hispanics and whites, respectively. These disparities persisted among high and low poverty neighborhoods and among both privately- and publicly-insured patients. Notably profound declines in both deceased and living donor graft survival rates for black, compared to white and Hispanic, children preceded the 3-year mark when transplant Medicare eligibility ends. Further research is needed to identify the unique barriers to long-term graft success among black pediatric transplant recipients.