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Impact of the kidney allocation system on young pediatric recipients.

ABSTRACT: The kidney allocation system (KAS) altered pediatric candidate prioritization. We determined KAS's impact on pediatric kidney recipients by examining delayed graft function (DGF) rates from 2010 to 2016. A propensity score-matched pediatric recipients pre- and post-KAS. A semiparametric decomposition analysis estimated the contributions of KAS-related changes in donor characteristics and dialysis time on DGF rate. The unadjusted odds of DGF were 69% higher post-KAS for young (<10 years at listing) recipients (N = 1153, P = .02) but were not significantly increased for older pediatric (10-17 years at listing) recipients (N = 2624, P = .48). Post-KAS, young recipients received significantly fewer pediatric (<18 years) donor kidneys (21% vs 32%, P < .01) and had longer median pretransplant dialysis time (603 vs 435 days, P < .01). After propensity score matching, post-KAS status increased the odds of DGF in young recipients 71% (OR 1.71, 95% CI 1.01-2.46). In decomposition analysis, 24% of the higher DGF rate post-KAS was attributable to donor characteristics and 19% to increased recipient dialysis time. In a confirmatory survival analysis, DGF was associated with a 2.2 times higher risk of graft failure (aHR2.28, 95% CI 1.46-3.54). In conclusion, KAS may lead to worse graft survival outcomes in children. Allocation changes should be considered.

SUBMITTER: Parker WF

PROVIDER: S-EPMC6029615 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Impact of the kidney allocation system on young pediatric recipients.

Parker William Fiske WF Ross Lainie Friedman LF Richard Thistlethwaite J J Gallo Amy E AE

Clinical transplantation 20180314 4

The kidney allocation system (KAS) altered pediatric candidate prioritization. We determined KAS's impact on pediatric kidney recipients by examining delayed graft function (DGF) rates from 2010 to 2016. A propensity score-matched pediatric recipients pre- and post-KAS. A semiparametric decomposition analysis estimated the contributions of KAS-related changes in donor characteristics and dialysis time on DGF rate. The unadjusted odds of DGF were 69% higher post-KAS for young (<10 years at listin ...[more]

PMID: 29457274

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Project description:Rationale & objectiveThe national kidney allocation system (KAS) implemented in December 2014 in the United States redefined the start of waiting time from the time of waitlisting to the time of kidney failure. Waitlisting has declined post-KAS, but it is unknown if this is due to transplant center practices or changes in dialysis facility referral and evaluation. The purpose of this study was to assess the impact of the 2014 KAS policy change on referral and evaluation for transplantation among a population of incident and prevalent patients with kidney failure.Study designCohort study.Setting & participants37,676 incident (2012-2016) patients in Georgia, North Carolina, and South Carolina identified within the US Renal Data System at 9 transplant centers and followed through December 2017. A prevalent population of 6,079 patients from the same centers receiving maintenance dialysis in 2012 but not referred for transplantation in 2012.ExposureKAS era (pre-KAS vs post-KAS).OutcomeReferral for transplantation, start of transplant evaluation, and waitlisting.Analytical approachMultivariable time-dependent Cox models for the incident and prevalent population.ResultsAmong incident patients, KAS was associated with increased referrals (adjusted HR, 1.16 [95% CI, 1.12-1.20]) and evaluation starts among those referred (adjusted HR, 1.16 [95% CI, 1.10-1.21]), decreased overall waitlisting (adjusted HR, 0.70 [95% CI, 0.65-0.76]), and lower rates of active waitlisting among those evaluated compared to the pre-KAS era (adjusted HR, 0.81 [95% CI, 0.74-0.90]). Among the prevalent population, KAS was associated with increases in overall waitlisting (adjusted HR, 1.74 [95% CI, 1.15-2.63]) and active waitlisting among those evaluated (adjusted HR, 2.01 [95% CI, 1.16-3.49]), but had no significant impact on referral or evaluation starts among those referred.LimitationsLimited to 3 states, residual confounding.ConclusionsIn the southeastern United States, the impact of KAS on steps to transplantation was different among incident and prevalent patients with kidney failure. Dialysis facilities referred more incident patients and transplant centers evaluated more incident patients after implementation of KAS, but fewer evaluated patients were placed onto the waitlist. Changes in dialysis facility and transplant center behaviors after KAS implementation may have influenced the observed changes in access to transplantation.

Project description:Background: Tacrolimus (TAC) and mycophenolic acid (MPA) are the main immunosuppressive drugs used in pediatric kidney transplantation. Single nucleotide polymorphisms (SNPs) in metabolizing enzymes and transporters might influence plasma levels of these drugs. Herein, we sought to determine the influence of SNPs on CYP3A5, MRP2 and UGT1A9 genes in Chilean pediatric kidney recipients using TAC and MPA. Patients and Methods: A prospective study was performed on 104 pediatric kidney recipients that used TAC and MPA for immunosuppression. The median age at the time of transplantation was 8.1 years [Q1-Q3 4.5-11.6 years] and the main clinical diagnosis was a structural anomaly. In a subgroup of patients, a complete steroid withdrawal was made at day 7. The CYP3A5 polymorphism (ancestral allele *1; variant allele *3) was determined in the entire cohort, while MRP2 -24G > A, UGT1A9 -275T > A, and UGT1A9 -2152C > T polymorphisms were determined in 53 patients. Genotypes were associated with trough drug concentrations (C0), dose requirements normalized by weight (TAC-D mg/kg) or body surface (MPA-D mg/m2), trough levels normalized by dose requirements (C0/D), and area under the curve in 12 h normalized by dose requirements (AUC0-12h/D). Results: The frequencies of the variant alleles CYP3A5*3, MRP2-24A, UGT1A9-275A, and UGT1A9-2152T were 76.9, 22.1, 6.6, and 2.9%, respectively. AUC0-12h/TAC-D were 1.6-fold higher in CYP3A5*3/*3 patients than in CYP3A5*1 carriers (CYP3A5*1/*3 and CYP3A5*1/*1). When analyzing patients with steroid withdrawal, CYP3A5*3/*3 patients had 1.7-fold higher AUC0-12h/TAC-D than the other genotypes. Patients carrying the CYP3A5*3/*3 genotype had higher TAC-C0, lower TAC-D and higher TAC-C0/D, consistently in a 6-months follow-up. Creatinine clearance was stable during the follow-up, regardless of the genotype. No significant differences between MRP2 and UGT1A9 genotypes were observed in MPA-C0, MPA-D or MPA-C0/D. However, patients carrying the UGT1A9-275A allele had lower AUC0-12h/MPA-D than those carrying the UGT1A9-275T ancestral allele. Conclusions: These results support that CYP3A5 and UGT1A9 genotyping in pediatric recipients might be useful and advisable to guide TAC and MPA dosing and monitoring in children that undergo kidney transplantation.

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Impact of the kidney allocation system on young pediatric recipients.

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Impact of the kidney allocation system on young pediatric recipients.

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