Aquaporin 11 rs2276415 variant and progression of chronic kidney disease.

Abstract

The Aquaporin 11 (AQP11) rs2276415 variant has been implicated in kidney disease in Type 2 diabetes. Association of the AQP11 variant with chronic kidney disease (CKD) beyond diabetic nephropathy is unknown, with no studies reported in the Chinese population. We explored the risk of CKD progression associated with the AQP11 rs2276415 variant in a population-based study in China. We conducted a prospective cohort study of 620 participants with CKD (Stages 2-5 and who were not receiving dialysis) at the Nephrology Center of First Affiliated Hospital of Jiaxing University between July 2011 and December 2014 and followed up for 3 years. Incident CKD progression, defined as an increase in creatinine levels of at least 0.4 mg/dL (35 µmol/L) above baseline or maintenance dialysis initiation or transplantation, was examined by AQP11 genotypes. During the follow-up period, CKD progression developed in 170 individuals. Cumulative events-free survival was significantly dependent on AQP11 genotypes with an apparent gene-dose effect (log-rank P < 0.001). Adjusting for sex, age and major CKD risk factors, the A allele of AQP11 gene (GA + AA) increased the risk of CKD progression by 1.92 (95% confidence interval 1.31- 2.84). The AQP11 rs2276415 variant predicts CKD progression in the Chinese population, independent of traditional risk factors. Exploring the pathways mediating the association may shed light on novel therapeutic targets in the pathophysiology of CKD.