Pediatric Renal Transplant Research Articles

Clinical impact of complement deposition findings on biopsies in acute rejection episodes of pediatric renal transplant patients

IntroductionRejection is the most important problem for renal graft function and survival. Complement system plays a key role in immune responses from host to graft. It was demonstrated that complement system activation is related with renal fibrosis. We evaluate clinical impact of complement deposition findings on biopsies in acute rejection episodes of pediatric renal transplant patients. MethodDemographics of the patients, graft functions, acute rejection episodes and graft loss were recorded from data files of 165 pediatric renal transplant patients. Findings of 98 renal biopsies were retrospectively evaluated. ResultsThirty three patients with kidney transplant had 44 acute rejection episodes (32 pure cellular acute rejection episodes / 1 pure humoral acute rejection episode / 11 combined acute cellular and acute humoral rejection episodes) proven by biopsy. C1q staining was positive in 7 biopsies, C3 staining in 15 biopsies and, C4d staining in 15 biopsies. 26 patients had graft fibrosis. All patients with a rejection history had a significant decrease in GFR value during follow-up. Patients who did not have fibrotic changes in first biopsy had same level of deterioration of GFR when compared with patients who had fibrotic changes in first biopsy. ConclusionWe could not demonstrate a significant relation between complement deposition and renal fibrosis, and between complement deposition and GFR values. Our data demonstrated that graft outcomes and graft loss after acute rejection episodes cannot be predicted only with complement deposition on graft or only with graft fibrosis.

A Systematic Review of Multiple Linear Regression-Based Limited Sampling Strategies for Mycophenolic Acid Area Under the Concentration–Time Curve Estimation

Background and ObjectiveOne approach of therapeutic drug monitoring in the case of mycophenolic acid (MPA) is a limited sampling strategy (LSS), which allows the evaluation of the area under the concentration–time curve (AUC) based on few concentrations. The aim of this systematic review was to review the MPA LSSs and define the most frequent time points for MPA determination in patients with different indications for mycophenolate mofetil (MMF) administration.MethodsThe literature was comprehensively searched in July 2021 using PubMed, Scopus, and Medline databases. Original articles determining multiple linear regression (MLR)-based LSSs for MPA and its free form (fMPA) were included. Studies on enteric-coated mycophenolic sodium, previously established LSS, Bayesian estimator, and different than twice a day dosing were excluded. Data were analyzed separately for (1) adult renal transplant recipients, (2) adults with other than renal transplantation indication, and (3) for pediatric patients.ResultsA total of 27, 17, and 11 studies were found for groups 1, 2, and 3, respectively, and 126 MLR-based LSS formulae (n = 120 for MPA, n = 6 for fMPA) were included in the review. Three time-point equations were the most frequent. Four MPA LSSs: 2.8401 + 5.7435 × C0 + 0.2655 × C0.5 + 1.1546 × C1 + 2.8971 × C4 for adult renal transplant recipients, 1.783 + 1.248 × C1 + 0.888 × C2 + 8.027 × C4 for adults after islet transplantation, 0.10 + 11.15 × C0 + 0.42 × C1 + 2.80 × C2 for adults after heart transplantation, and 8.217 + 3.163 × C0 + 0.994 × C1 + 1.334 × C2 + 4.183 × C4 for pediatric renal transplant recipients, plus one fMPA LSS, 34.2 + 1.12 × C1 + 1.29 × C2 + 2.28 × C4 + 3.95 × C6 for adult liver transplant recipients, seemed to be the most promising and should be validated in independent patient groups before introduction into clinical practice. The LSSs for pediatric patients were few and not fully characterized. There were only a few fMPA LSSs although fMPA is a pharmacologically active form of the drug.ConclusionsThe review includes updated MPA LSSs, e.g., for different MPA formulations (suspension, dispersible tablets), generic form, and intravenous administration for adult and pediatric patients, and emphasizes the need of individual therapeutic approaches according to MMF indication. Five MLR-based MPA LSSs might be implemented into clinical practice after evaluation in independent groups of patients. Further studies are required, e.g., to establish fMPA LSS in pediatric patients.

Abstract 35 - The Paediatric Renal Transplant Recipient: A retrospective review of the changing trends of transplantation in Ireland

Abstract 35 - The Paediatric Renal Transplant Recipient: A retrospective review of the changing trends of transplantation in Ireland

Use of Rituximab for persistent EBV DNAemia, and Its effect on donor-specific antibody development in pediatric renal transplant recipients: A case series.

Persistent EBV DNAemia (PEBV) is associated with late-onset PTLD. The efficacy of rituximab in PEBV is not conclusive. We monitored PEBV and DSA in pediatric kidney transplant patients with or without rituximab. 13 PEBV patients received standard treatment with immunosuppression reduction and valganciclovir, with or without IVIG; 5/13 were further treated with rituximab. All Rituximab-treated and 6/7 No-Rituximab patients were EBV seronegative at transplant and seroconverted post-transplant. Peak EBV PCR levels were lower in No-Rituximab than Rituximab patients and all No-Rituximab patients cleared PEBV after standard treatment. Additional 1-2 doses of rituximab reduced EBV PCR levels in all 5 Rituximab patients, 3 cleared PEBV. One No-Rituximab patient developed localized PLTD. None of Rituximab patients developed de novo DSA, while 4/8 No-Rituximab patients did: 2/4 had ABMR. 1/5 Rituximab and 5/8 No-Rituximab patients had acute rejection. There was no change in eGFR between pre-EBV DNAemia and follow-up in Rituximab patients, while reduction in No-Rituximab patients was found. There was no difference in graft and patient survival. While early intervention with rituximab in pediatric patients with PEBV may reduce viral load and PTLD, we observed a slower development of de novo DSA, and rejection and maintenance of eGFR.

Development of CMV‐specific cytotoxic T cells (CMV‐Tc) in pediatric renal transplant recipients with CMV viremia

Viral infections are controlled primarily by viral-specific T cells, raising concern for adequate T-cell response to clear CMV infection in transplant recipients receiving lymphocyte-depleting agents (LDA). We examined the rates of CMV viremia and clearance, seroconversion, and CMV-specific CD8+ T cell (CMV-Tc) activity with class of induction agent received. Retrospective review of 45 pediatric renal transplant recipients who received induction with LDA (n=31) or non-LDA (NLDA; n=14) received valganciclovir prophylaxis for 6months post-transplant and CMV-PCR monitoring. CMV-Tc was measured by intracellular IFNγ flow cytometry, when possible, at baseline, 1month after CMV viremia (>5 copies/PCR) and serially until CMV-Tc was positive (≥0.2%). Viremia rates at 1, 2, and 4years post-transplant were higher in LDA vs. NLDA (46.3% vs. 7.2%, 64.2% vs. 7.2%, and 64.2% vs. 7.2%, respectively; p=.002). Viremia rates at these time points in seronegative LDA (50.3%, 71.6%, 71.6%) were significantly or near significantly higher than seronegative NLDA (9.1%, 9.1%, 9.1%; p=.004), seropositive-LDA (22.3%, 22.3%, 22.3%; p=.07), or seropositive NLDA (0%, 0%, 0%; p=.07). Eleven of 17 (64.7%) viremic subjects required valganciclovir dose reduction during the prophylaxis period for leukopenia. All viremic LDA patients developed CMV-Tc. One viremic NLDA patient did not develop CMV-Tc. No patients developed CMV disease. CMV seronegative pediatric renal transplant patients receiving LDA are more likely to have valganciclovir prophylaxis dose reduction and develop subclinical CMV viremia; however, all developed CMV-Tc. Larger prospective studies are needed to further understand the effects of induction agents on CMV-Tc and CMV-Tc's role post-transplant.

Long-term outcome of early steroid withdrawal in pediatric renal transplantation.

Steroid use in renal transplant is related to multiple adverse effects. Long-term effects of early withdrawal steroids in pediatric renal transplant were assessed. Renal transplant children with low immunological risk treated on basiliximab, tacrolimus, and mycophenolate with steroid withdrawal or steroid control were evaluated between 2003 and 2019. Clinical variables, treatment adherence, acute rejection, graft loss, and death were analyzed through hazard ratios, and Kaplan-Meier and multivariate analyses. The study included 152 patients, 71.1% steroid withdrawal, mean follow-up 8.5years, 64.5% structural abnormalities, and 81.6% deceased donor. At 12years of transplant, event-free survival analysis for graft loss or death showed no significant difference between steroid withdrawal and control steroid treatment (85.9% vs. 80.4%, p=.36) nor in acute rejection at 10years (18.5% vs. 20.5%, p=.78) or in donor-specific antibody appearance (19.6% vs. 21.4%, p=.98). Delta height Z-score was increased in the steroid withdrawal group (p<.01). The main predictor of graft loss or death was non-adherence to treatment (p=.001; OR: 17.5 [3.3-90.9]). Steroid withdrawal therapy was effective and safe for low-risk pediatric renal transplant in long-term evaluation. Non-adherence was the main predictor of graft loss or death.

Thromboprophylaxis after kidney transplantation in children: Ten-year experience of a single Brazilian center.

Kidney transplantation is the gold standard treatment for children with end-stage chronic kidney disease. Graft thrombosis is an important cause of graft failure, with high morbidity, mortality, and impact on quality of life and to the health system. The role of thromboprophylaxis in this setting is still uncertain. We describe the demographic characteristics and thrombotic risk factors in pediatric renal transplant recipients, determining the rate of renal graft thrombosis, and discuss the role of thromboprophylaxis. This retrospective study reviewed 96 pediatric renal transplantations between 2008 and 2017 in a single hospital. Patients were assigned to one of two groups: children who did not receive thromboprophylaxis after transplantation and those who did. We reported their characteristics, comparing the incidence of graft thrombosis and hemorrhagic complications between the groups. Forty-nine patients (51%) received thromboprophylaxis. Thrombosis occurred in 5 patients who did not receive thromboprophylaxis (5.2%) compared with none in the group that did (p=.025). In all patients, renal graft thrombosis resulted in early graft loss. Thirteen patients had hemorrhagic complications. Seven were unrelated to pharmacological thromboprophylaxis (2major, 1moderate, and 4minor bleeding, which either did not receive thromboprophylaxis or had bleeding prior to thromboprophylaxis), while six occurred during heparinization (2major, 1moderate, and 3minor bleeding). There was no significant difference in the rate of hemorrhagic complications between the groups (p=.105). The rate of renal graft thrombosis was 5.2%. Thrombosis remains an important cause of early graft loss. Thromboprophylaxis was associated with a reduction in graft thrombosis without increased risk of bleeding.

A systematic review of outcomes of Deflux® treatment for vesicoureteral reflux following pediatric renal transplantation

Vesicoureteral reflux (VUR) after renal transplant in the pediatric population may be associated with an increased incidence of urinary tract infection (UTIs) leading to increased morbidity, including graft dysfunction and graft loss. The non-orthotopic location of the transplanted ureter, and lack of submucosal tunnel may pose challenges in correcting the VUR using endoscopic injection techniques. Herein we report the results of a systematic review evaluating the outcomes of endoscopic treatment of VUR using Deflux® in this population. Pubmed and Embase databases were searched from October 2001 to April 2019. Full-text English articles involving patients less than 18 years old at the time of transplant, with a diagnosis of VUR post-transplantation, who underwent Deflux® treatment were included. Figure1 outlines our PRISMA-compliant search strategy. We found 6 eligible studies describing Deflux® treatment outcomes in 67 pediatric patients with post-transplant VUR where voiding cystourethrogram (VCUG) confirmed the diagnosis and resolution of VUR. The mean success rate was 36.8%. Ureteral obstruction occurred in 7/67 cases (10.4%). In all these 7 cases of obstruction, ureteric stenting was the initial management, but was only successful in 1 patient. Open ureteroneocystostomy (UNC) was performed in 4/7 cases, while 2/7 were managed expectantly (unknown outcomes). Persistent VUR with UTI despite Deflux® were reported in 20 out of 67 cases. Of these, 7 were managed with prophylactic antibiotics, and 13 with UNC. Success rates were consistently low for UNC after failed Deflux® in comparison to redo UNC in transplant ureters without prior injection. Low success rates are seen following injection techniques for VUR after pediatric renal transplant. Although an appealing option, Deflux® may prove counterintuitive due to the high rate of obstruction and suboptimal results if open reimplantation is required. A multi-institutional prospective study with a larger population size may further elucidate these results.

Impact of CYP3A5 phenotype on tacrolimus time in therapeutic range and clinical outcomes in pediatric renal and heart transplant recipients.

This study investigated the effect of CYP3A5 phenotype on time in therapeutic range (TTR) of tacrolimus post-transplant in pediatric patients. This retrospective study assessed medical records of pediatric kidney and heart recipients with available CYP3A5 genotype for tacrolimus dosing, troughs, and the clinical events (biopsy-proven acute rejection [BPAR] and de novo donor-specific antibodies [dnDSA]). The primary outcome, mean TTR in the first 90days post-transplant, was 9.0% (95% CI: -16.1, -1.9) lower in CYP3A5 expressers (p=0.014) when adjusting for time to therapeutic concentration and organ type. There was no difference between CYP3A5 phenotypes in time to the first clinical event using TTR during the first 90days. When applying TTR over the first year, there was a significant difference in event-free survival (EFS) which was 50.0% for CYP3A5 expressers/TTR<35%, 45.5% for expressers/TTR≥35%, 38.1% for nonexpressers/TTR<35%, and 72.9% for nonexpressers/TTR≥35% (log-rank p=0.03). A post hoc analysis of EFS identified CYP3A5 expressers had lower EFS compared to nonexpressers in patients with TTR≥35% (p=0.04) but no difference among patients with TTR<35% (p=0.6). The relationship between TTR and CYP3A5 phenotype suggests that achieving a TTR≥35% during the first year may be a modifiable factor to attenuate the risk of BPAR and dnDSA.

Pediatric kidney transplantation, a technical update.

Pediatric kidney transplantation is the definitive therapy for infants and children suffering from renal failure. It is a distinct endeavor demanding specialized care for optimal results. This includes a dedicated preoperative workup accounting for unique predisposing urologic conditions, specialized surgical techniques, and careful hemodynamic monitoring and maintenance. Historically, size-matched renal allografts from pediatric donors to pediatric recipients suffered from poor outcomes. Advances in surgical technique performed at high volume centers have shown that these operations can be performed safely, helping expand the donor pool for these patients. Concurrently, transplantation of increasingly small for size infants with complex medical and surgical backgrounds has become a reality. On a policy front, efforts to expand access to size-matched organs, combined with advances in medical management and immunosuppression have seen pediatric renal transplantation reach new heights. Now, these breakthroughs are heightened by the ability to transplant such organs into the smallest infants. The net result will be diminished transplant waiting times and, accordingly, improved quality of life and longevity for children suffering from renal failure.

The utility of native ureter in the management of ureteral complications in children after renal transplantation.

Ureteral complications after renal transplantation in children are a major source of morbidity. Management is complex and variable. With IRB approval, health records were retrospectively reviewed of patients who: were <18years, underwent kidney transplant between 1997 and 2017, had at least 2years of follow-up, and underwent interventions due to post-transplant ureteral complications. Of 136 patients, seventeen (13%) required ureteral intervention due to stricture (n=3), reflux (n=12), or both (n=2). Transplant occurred at median 10.5years (3.1-14.7). Reconstruction occurred at median 10months (7-15) after transplant. Pre-existing bladder pathology was present in 6 (35%) patients. Four of five patients with strictures had at least one endoscopic balloon dilation. Ultimate management included reimplantation, ureteroureterostomy of native to transplant ureter, pyeloureterostomy to native ureter, multiple endoscopic interventions followed by a Boari flap, or multiple failed endoscopic interventions. Fourteen patients with VUR underwent reimplantation (n=5), ureteroureterostomyof native to transplant ureter (n=4), pyeloureterostomyto native ureter (n=4), and one underwent endoscopic injection with Deflux of the transplant ureter. Only one patient had a non-functioning graft due to ureteral complication. All patients were alive at follow-up (median 17years [12-19]). Transplant ureteral reflux and stricture are significant complications following pediatric renal transplantation and may require surgical management. In our population, reflux or stricture requiring ureteral reconstruction occurred in 10% and 4%, respectively. Endoscopic interventions were rarely successful. Native ureters were used for ureteral reconstruction in more than two thirds of patients should be considered in management of ureteral complications.

Course of renal allograft function after diagnosis and treatment of post-transplant lymphoproliferative disorders in pediatric kidney transplant recipients.

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. 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 (375mg/m2 ) 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 60months after PTLD. Twenty patients were included in this cohort analysis. Median time from transplantation to PTLD was 2.4years. Histopathology showed monomorphic lesions in 16 and polymorphic in 4 patients. Two patients experienced PTLD relapse after 2 and 14months. 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 5.3years after diagnosis of PTLD. Another patient developed recurrence of primary renal disease (focal-segmental glomerulosclerosis) and lost his renal allograft 3.8years post-transplant (2.0years after PTLD diagnosis). 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.

Improved renal allograft survival for pre-emptive paediatric renal transplant recipients in the UK

BackgroundThe aim of this study was to investigate whether being on dialysis at the time of renal transplantation affected renal allograft survival in paediatric renal transplant recipients (pRTRs).MethodsRetrospective study of...

Association of Calculated Area under the Curve or Cyclosporine C0 and C2 Level Monitoring in Pediatric Renal Transplant Patients

Cyclosporine A (CsA) is highly variable pharmacokinetically and has a narrow therapeutic window; the serum level of patients treated with CsA must be monitored carefully. We investigated the trough and second-hour serum levels of CsA, the calculated area under the curve (AUC), and their association of those factors with chronic allograft dysfunction in pediatric patients.

The impact of multiple donor renal arteries on perioperative complications and allograft survival in paediatric renal transplantation

The impact of using allografts with multiple renal arteries in paediatric kidney transplantation has not been clearly established. The aim of this study was to determine whether kidney grafts with multiple arteries pose any adverse effects upon perioperative surgical outcomes, and graft survival up to 12 months post-transplant. The objective of this study was to perform a comparative analysis of a minimum of 12-month graft survival and transplant renal function in paediatric renal transplant recipients receiving single versus multiple donor arteries, and to assess perioperative and early post-operative surgical outcomes. A retrospective divisional chart review of 379 transplants performed (2000-2018), of which 90 (23.7%) contained multiple donor arteries. The number of arteries of the graft, donor type, vascular reconstruction technique, occurrence of urological and vascular complications, estimated GFR and graft survival up to 12 months post-transplantation, graft loss and mortality were analysed. Comparisons in baseline characteristics and outcome measures were made between both groups. No significant differences were found in age (p=0.42), BMI (p=0.39), estimated intraoperative blood loss (p=0.14), overall (p=0.63) or warm ischaemic time (p=0.37). 51.3% patients with multiple donor arteries underwent an exvivo reconstruction. There were no differences in the site of arterial anastomosis (aorta, external iliac, internal iliac), or anastomotic type (end-side; end-end). Whilst there was a significantly higher post-operative lymphocoele rate in the multiple vessel cohort (p=0.024), there was no increase in post-transplant urine leaks, rejection episodes, graft loss (1.1% multiple vs 2.1% single), perioperative complications (p=0.68), or estimated GFR at 1 month (p=0.9) or at 1 year (p=0.67). We demonstrated in this study that there was no significant difference in postoperative complications up to 3 months, eGFR and renal function up to 1 year, and graft survival up to 4 years post transplantation irrespective of allograft type or reconstruction technique. There was however, a higher rate of lymphocoeles in the multiple artery cohort. The results seen here broadly mirror trends seen in adult studies, however, there is little data available from paediatric series. Our study demonstrates that multiple renal artery allografts - previously been considered to carry a high complication risk - can be safely used for paediatric renal transplantation with equivalent perioperative complications and graft outcomes to single artery allografts.

Utility of pre-transplant lower urinary tract investigation in pediatric renal transplant population after referral: A 16-year institutional experience.

To evaluate the clinical utility of pre-renal transplant LUT investigations in pediatric populations after their referral for transplant evaluation based on the etiology of their ESRD. A 16year retrospective review of patients undergoing RT performed at our institution was performed. Patients were stratified into two groups: Group 1-non-urologic and Group 2-urologic etiology for ESRD. Baseline characteristics, pre-transplant LUT investigations, and urologic interventions were assessed. One-year clinical outcomes were compared between those with and without LUT investigations following referral for renal transplantation (RT). 227 patients and 97 patients were identified for Groups 1 and 2, respectively. 19% of Group 1 and 73% of Group 2 had VCUG, while 1% and 13%, respectively, had UDS ordered following referral for RT. In both groups, >50% of VCUG and UDS were ordered without specific clinical concerns. These had low likelihood of prompting interventions, both pre-transplant (Group 1-VCUG 0%, UDS 0%; Group 2-VCUG 0%, UDS 8%) or post-transplant (Group 1-0%, Group 2-5%). In both groups, LUT investigation following referral for RT did not lead to differences in 1year outcomes assessed. In anticipation of pediatric RT, LUT investigations ordered without clinical indications did not provide information that altered management prior to transplantation.

Hemoglobin and Cholesterol Affect Apparent Tacrolimus Clearance in Pediatric Transplant Recipients – a Retrospective Cohort Study

Introduction: Tacrolimus has a narrow therapeutic index with substantial inter- and intra-patient variability. Factors beyond genetic and developmental factors are poorly understood. Recent adult studies suggest that hemoglobin affects the apparent clearance (CL/F), whereas this and other potential factors in children are understudied. Methods: After ethics approval, we performed a single center retrospective cohort study of pediatric renal transplant recipients, who were followed between January 1st, 2004, and June 30th, 2018. Patients without tacrolimus therapy or concomitant sirolimus were excluded. The aim was to show the impact of hemoglobin, albumin, cholesterol and HDL on the apparent tacrolimus clearance (CL/F = Dose/AUC). Data were collected from electronic health record. We used 12-point pharmacokinetic (PK) profiles. Results: Thirty-three patients were included. Median age at transplantation was 10 years, 52% were female, the median tacrolimus area under the curve (AUC) was 133 ng*h/mL. CL/F mainly correlated with hemoglobin (n=1,257, r=-0.3767, p&lt;0.0001), HDL-cholesterol (n=236, r=-0.3973, p&lt;0.0001) and total cholesterol (n=373, r=-0.1821, p=0.0004). Conclusion: The present study suggests a moderate impact of the biochemical factors studied in the tacrolimus CL/F. Lower hemoglobin seems to increase it, while higher cholesterol decreases it. Physicians should be aware of this association during the TDM follow up.

Evaluating the Impact of CYP3A5 Genotype on Post-Transplant Healthcare Resource Utilization in Pediatric Renal and Heart Transplant Recipients Receiving Tacrolimus.

PurposeCYP3A5 genotype is a significant contributor to inter-individual tacrolimus exposure and may impact the time required to achieve therapeutic concentrations and number of tacrolimus dose adjustments in transplant patients. Increased modifications to tacrolimus therapy may indicate a higher burden on healthcare resources. The purpose of this study was to evaluate whether CYP3A5 genotype was predictive of healthcare resource utilization in pediatric renal and heart transplant recipients.Patients and MethodsPatients <18 years of age with a renal or heart transplant between 6/1/2014–12/31/2018 and tacrolimus-based immunosuppression were included. Secondary use samples were obtained for CYP3A5 genotyping. Clinical data was retrospectively collected from the electronic medical record. Healthcare resource utilization measures included the number of dose changes, number of tacrolimus concentrations, length of stay, number of clinical encounters, and total charges within the first year post-transplant. Rejection and donor-specific antibody (DSA) formation within the first year were also collected. The impact of CYP3A5 genotype was evaluated via univariate analysis for the first year and multivariable analysis at 30, 90, 180, 270, and 365 days post-transplant.ResultsEighty-five subjects were included, 48 renal transplant recipients and 37 heart transplant recipients. CYP3A5 genotype was not associated with any outcomes in renal transplant, however, a CYP3A5 expresser phenotype was a predictor of more dose changes, more tacrolimus concentrations, longer length of stay, and higher total charges in heart transplant recipients. CYP3A5 genotype was not associated with rejection or DSA formation. Age and induction therapy were associated with higher total charges.ConclusionCYP3A5 genotype may predict healthcare resource utilization in the first year post-transplant, although this may be mitigated by differences in tacrolimus management. Future studies should evaluate the impact of genotype-guided dosing strategies for tacrolimus on healthcare utilization resources.

Renal Transplant in Pediatric Patients With Congenital Abnormalities of the Lower Urinary Tract

Congenital abnormalities of the lower urinary tract can result in end-stage renal disease and are responsible for a significant number of renal transplants. Management of these patients is not always consensual, and more evidence is required about the frequency of associated complications. Our aim was to report the experience of a Pediatric Renal Transplant Unit with renal transplant in pediatric patients with congenital abnormalities of the lower urinary tract. Data on renal transplants performed in pediatric patients with congenital abnormalities of the lower urinary tract between January 1, 2009, and December 31, 2019, in this center were retrospectively reviewed. Fifty-three pediatric renal transplants were performed in the institution during the considered time period. Of these, 26 transplants were performed in 24 patients with congenital abnormalities of the lower urinary tract, and 14 were male. The median age at the time of renal transplant was 10.5 years (interquartile range, 5.25-15 years), and the most frequent diagnoses were neurogenic bladder (n = 7; 29%) and posterior urethral valve (n = 7; 29%). Three patients (13%) underwent preemptive renal transplant, 15 were on peritoneal dialysis (63%), and 6 were on hemodialysis (25%). A total of 81 pyelonephritides were diagnosed in the 24 patients, mostly attributed to Escherichia coli, followed by Klebsiella pneumonia. The median follow-up was 92.5 months (interquartile range, 52.3-114 months). For patients with congenital abnormalities of the lower urinary tract, graft survival was 92.3% at 1, 5, and 10 years, with no deaths reported. Renal transplant is the treatment of choice for pediatric patients with end-stage renal disease. The procedure does not seem to be associated with worse patient outcomes. Additionally, despite the significant number of pyelonephritides cases, it does not seem to result in decreased graft or patient survival.

Immunological Risk Factors in Paediatric Kidney Transplantation.

PurposeThe aim of this study was to identify factors impacting recipient sensitization rates and paediatric renal transplant patient outcomes.Patients and MethodsFor this purpose, a retrospective analysis of 143 paediatric renal transplants was carried out. This included the evaluation of patient’s and donor’s demographic data, HLA mismatches, immunosuppressive therapy, rejection episodes, panel reactive antibody (PRA) and post-transplant lymphoproliferative disease (PTLD).ResultsThe mean patient age at the point of transplant receival was 11.5 years with a mean follow up time of 9.33±5.05 years. It was noted that graft survival rates for donors over 59 years had the worst outcome. HLA match did not show statistically significant influence on graft outcome. Graft survival for more than one biopsy-proven rejection was also significantly shorter (p=0.008). PRA were found in 28% of the recipient’s post-transplantation and showed association with lower graft survival rates (p<0.001). In the present study, 22.7% (5/22) of the patients with EBV infections presented a PTLD.ConclusionIn conclusion, good graft survival with reduced sensitization for future transplantations and minimize the risk of PTLD, can be ensured through a balance between donor age, HLA match and condition of the recipient should be sought. Furthermore, paediatric patients should preferably receive organs from donors between the age of 10 and 59. EBV infection could be a relevant factor for developing PTLD.