POTENTIAL SIGNIFICANCE OF BRADYKININ 2 RECEPTOR GENOTYPING IN KIDNEY TRANSPLANT RECIPIENTS

Katarina Danković,Tatjana Cvetković,Mina Cvetković,Goran Paunović,Radmila Veličković-Radovanović,Branka Mitić,Nikola Stefanović

doi:10.5633/amm.2021.0103

Abstract

Bradykinin (BK), a vasoactive peptide, is considered to exert the renoprotective and cardioprotective effects. Furthermore, most of its effects are mediated by the activation of BK type 2 receptor (B2R), whose level of expression is influenced by insertion/deletion (+9/-9) gene polymorphism. The aim of this study was to investigate the potential influence of B2R +9/-9 gene polymorphism on kidney function and blood pressure in kidney transplant recipients (KTRs) within the first post-transplantation year. Secondary, the study analyzed the correlation between hypertensive status and graft function, with respect to the B2R +9/-9 gene polymorphism. The pharmacogenetic study included 95 KTRs with clinical and biochemical parameters evaluated in three time-points (3rd, 6th, 12th month). The graft function was assessed using the estimated glomerular filtration rate (eGFR), while systolic (SBP), diastolic (DBP), and mean blood pressure (MAP) were used as parameters for the evaluation of blood pressure control. The carriers of -9/-9 genotype had more stable graft function compared to both, heterozygotes and homozygous for +9 allele, not only in the early (up to 6 months) but as well in the late post-transplantation period (beyond 6 months). Also, the -9/-9 genotype carriers showed a tendency to significantly decrease MAP, SBP, and DBP in the observed period, whereby only in this patient group the significant association between hypertensive status and graft function was demonstrated. In conclusion, genotyping of B2R +9/-9 gene polymorphism alongside with biochemical and clinical parameters may identify patients with respect to the risk of more prompt decline of graft function.

Highlights

Kidney transplantation (Tx) is the optimal treatment choice for patients with end-stage kidney disease
The main goal of the study was to investigate whether the BK type 2 receptor (B2R) +9/-9 gene polymorphism might have influenced the graft function and blood pressure or not, in the first year after Tx
Genotype frequencies did not deviate from Hardy– Weinberg equilibrium (HWE) (p > 0.05) for tested B2R polymorphism: χ2 = 0.90, p = 0.34

Summary

Introduction

Kidney transplantation (Tx) is the optimal treatment choice for patients with end-stage kidney disease. Kidney transplant recipients (KTRs) are considered to have chronic kidney www.medfak.ni.ac.rs/amm disease, even immediately after Tx, whereas the incidence of cardiovascular morbidity and mortality is higher compared to the general population. Some patients exert rapid and pronounced decline in kidney function, while others have stable graft function [3]. It seems important to identify the components of the organism that can affect transplanted kidney in positive (renoprotective) or negative manner. Some scientists suggest that kinins exert hemodynamic effects primarily in the heart and kidney, affecting the local redistribution of blood flow and perfusion within these organs [7]

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