Higher plasma renin activity is associated with increased kidney damage risk in patients with hypertension and glucose metabolic disorders

Abstract

The impact of renin on kidney remain unclear among hypertensives with glucose metabolic disorders (GMD). We aimed to evaluate the association between plasma renin activity (PRA) and kidney damage in hypertensive patients with GMD. Overall, 2033 inpatients with hypertension and GMD free of chronic kidney disease (CKD) at baseline were included. CKD was defined using estimated glomerular filtration rate (eGFR) and urine protein. PRA was treated as continuous variable, and also dichotomized as high (≥0.65) or low (< 0.65) groups. The association of PRA with incident CKD was evaluated using multivariable Cox model controlling for antihypertensive medications and baseline aldosterone, and traditional parameters. Subgroup and interaction analyses were performed to evaluate heterogeneity. During a median follow-up of 31 months, 291 participants developed CKD. The incidence was higher in high-renin group than that in low-renin group (54.6 vs 36.6/1000 person-years). Significant association was observed between PRA and incident CKD, and the association was mainly driven by an increased risk for proteinuria. Each standard deviation increment in log-transformed PRA was associated with 16.7% increased risk of proteinuria (hazard ratio = 1.167, P = .03); compared with low-renin group, there was 78.4% increased risk for high-renin group (hazard ratio = 1.784, P = .001). Nonlinear associations were observed between PRA and kidney damage. Higher PRA is associated with greater risk of incident kidney damage, especially for positive proteinuria, in patients with coexistence of hypertension and diabetes, independent of aldosterone. In this patient population with high risk for kidney damage, PRA may serve as an important predictor.

Keywords: chronic kidney disease; diabetes; hypertension; renin; risk factors.

FIGURE 1

Flow diagram of patient enrollment. GMD, glucose metabolic disorders; CVD, cardiovascular disease; CKD, chronic kidney disease

FIGURE 2

Kaplan–Meier curve of cumulative incidence of renal impairment based on high‐ and low‐PRA. PRA, plasma renin activity; CKD, chronic kidney disease; DRF, decreased renal function. P value was generated based on log‐rank test

FIGURE 3

Restricted cubic splines for the shape of the association of PRA with CKD (A) and proteinuria (B). PRA, plasma renin activity; CKD, chronic kidney disease

FIGURE 4

Stratification analysis on association between PRA and proteinuria. Results were derived from multivariate Cox regression and presented as hazard ratio for high PRA (compared with low PRA). Multivariate Model adjusted for Age, Sex, Drinking, SBP, Duration of HTN, HbA1c, GMD type, TC, HDL‐C, Baseline eGFR, BUN, UA, K⁺, Hypoglycemic therapy, Antihypertensive agents, and log‐PAC. PRA, plasma renin activity; GMD, glucose metabolism disorders; PAC, plasma aldosterone concentration