Tacrolimus 22 [HRP]

Background: Acute kidney injury (AKI) is common in children following surgery for congenital heart disease and has been associated with poor long-term kidney outcomes. Children undergoing heart transplantation may be at increased risk for the development of both AKI and chronic kidney disease (CKD). This study examines AKI rates in children, adolescents, and young adults after heart transplantation and analyzes the relationship between AKI and CKD in this population. Study Design: Retrospective cohort study. Setting & Participants: 88 young patients who underwent heart transplantation at Lucile Packard Children's Hospital, Stanford, CA, September 1, 2007, to November 30, 2013. Predictor: The primary independent variable was AKI within the first 7 postoperative days, ascertained according to the KDIGO (Kidney Disease: Improving Global Outcomes) creatinine criteria (increase in serum creatinine >= 1.5 times baseline within 7 days). Outcomes: Recovery from AKI at 3 months, ascertained as serum creatinine level, 1.5 times baseline; and development of CKD at 6 and 12 months, ascertained as estimated glomerular filtration rate, 60 mL/min/1.73 m(2) for more than 3 months. Results: 63 (72%) patients developed AKI; 57% had moderate (stage 2 or severe stage 3) disease. Recovery occurred in 39 of 63 (62%), 50% for stage 2 or 3 versus 78% for stage 1 (P = 0.04). At 6 and 12 months, 3 of 82 (4%) and 4 of 76 (5%) developed CKD, respectively. At both time points, CKD was more common in those without recovery (3/22 [14%] vs 0/38 (0%); P = 0.04, and 3/17 (18%) vs (0/34) 0%; P = 0.03, respectively). Limitations: Retrospective design, small sample size, and single-center nature of the study. Conclusions: AKI is common after heart transplantation in children, adolescents, and young adults. Nonrecovery from AKI is more common in patients with more severe AKI and is associated with the development of CKD during the first year. (C) 2016 by the National Kidney Foundation, Inc.

This work investigated, in two large cohorts of French renal transplants treated with tacrolimus, the influence of donor and recipient ABCB1, CYP3A4, and CYP3A5 genotypes on the risk of allograft loss. A discovery and a replication population of 330 and 369 adult renal transplant patients, each from a different transplantation center and all receiving a tacrolimus-based immunosuppressive regimen, were retrospectively genotyped. The influence of genetic factors and other known risk factors on allograft loss was investigated using multivariate Cox proportional hazard analyses. The existence of previous transplantations (per unit HR = 1.89 [1.10-3.26] P = .0216) and the donor ABCB1 c.1199GA/AA genotype (GA/AAvs GG: HR = 3.22 [1.14-9.09], P = .0288) were associated with an increased risk of allograft loss in the discovery cohort and with graft loss due to humoral rejection in the replication cohort (per unit HR = 2.26 [1.34-3.81], P = .00229; GA/AAvs GG HR = 3.42 [1.28-9.16], P = .0142). Genotyping the donor for the ABCB1 c.1199 G>A (exon 11, rs2229109) allele may be of interest before prescribing tacrolimus to the recipient, although this polymorphism is rather rare and its effect may be limited to certain mechanisms of graft loss.