Neuropeptide y and chronic kidney disease progression: A cohort study

Abstract

Background. Neuropeptide Y (NPY) is a sympathetic neurotransmitter that has been implicated in various disorders including obesity, gastrointestinal and cardiovascular diseases. Methods. We investigated the relationship between circulating NPY and the progression of the glomerular filtration rate (GFR) and proteinuria and the risk for a combined renal endpoint (>30% GFR loss, dialysis/transplantation) in two European chronic kidney disease (CKD) cohorts including follow-up of 753 and 576 patients for 36 and 57months, respectively. Results. Average plasma NPY was 104632 pmol/L in the first CKD cohort and 119641 pmol/L in the second one. In separate analyses of the two cohorts, NPY associated with the progression of the estimated GFR (eGFR) and proteinuria over time in both unadjusted and adjusted {eGFR: 3.60 mL/min/1.73 m2 [95% confidence interval (CI): 4.46 to2.74] P<0.001 and 0.83mL/min/1.73m2 (1.41 to0.25, P 0.005); proteinuria: 0.18 g/24 h (0.11 0.25) P<0.001 and 0.07 g/24 h (0.005 0.14) P 0.033} analyses by the mixed linear model. Accordingly, in a combined analysis of the two cohorts accounting for the competitive risk of death (Fine and Gray model), NPY predicted (P 0.005) the renal endpoint [sub-distribution hazard ratio (SHR): 1.09; 95% CI: 1.03 1.16; P 0.005] and the SHR in the first cohort (1.14, 95% CI: 1.04 1.25) did not differ (P 0.25) from that in the second cohort (1.06, 95% CI: 0.98 1.15). Conclusions. NPY associates with proteinuria and faster CKD progression as well as with a higher risk of kidney failure. These findings suggest that the sympathetic system and/or properties intrinsic to the NPYmoleculemay play a role in CKD progression.