Effect of leptin concentrations and leptin receptor gene polymorphisms on the outcome of renal transplantation.

Abstract

Leptin is a pro-inflammatory adipocytokine implicated in cardiovascular disease, insulin resistance, obesity and chronic kidney disease. In a cohort of 236 renal transplant recipients, we aimed to determine whether circulating leptin concentrations and/or three polymorphisms in the leptin receptor (LEPR) gene, namely rs1137100, rs1137101 and rs1805094, were related to clinical outcomes in renal transplantation. Plasma leptin concentrations were measured by ELISA. Genetic variants were determined by conventional real-time PCR assays, and statistical associations with clinical outcomes were obtained by logistic regression modelling. Patients with elevated leptin levels were at higher risk of acute rejection (OR = 1.03 (1.01-1.05), p = 0.03) and displayed worse renal clearance (p = 0.001) than patients with lower levels. Leptin levels were not significantly affected by any of the three LEPR SNPs. The rs1137101 G variant showed an inverse association with the risk of delayed graft function (DGF) (OR = 0.42 (0.22-0.81), p = 0.009), whilst the homozygous rs1805094 CC genotype was associated with increased risk of acute rejection (OR = 11.38 (2.15-60.16), p = 0.004). A statistically significant association was also observed between the rs1137100 GG genotype and better renal function [mean difference vs. AA/AG = 20.20 (4.91-35.49) ml/min, p = 0.010]. Our results show that both leptin plasma concentrations and polymorphisms in the LEPR gene may affect clinical outcomes in renal transplant recipients, suggesting that the determination of these parameters could be useful in predicting post-transplant adverse events.