Abstract 073: The Association Between Plasma Soluble Prorenin Receptor and Renin Activity Points Toward Renin Angiotensin System Activation and Cardiovascular Complications in Women With Type-2 Diabetes

Abstract

Activation of the renin-angiotensin system (RAS) increases the risk of hypertension and chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T2DM). The prorenin receptor (PRR), a component of the RAS, activates prorenin via a non-catalytic mechanism. High levels of the soluble form of PRR (sPRR) have been reported in patients with cardiovascular (CV) diseases, including essential hypertension, CKD, preeclampsia, and gestational diabetes. Increased systemic prorenin in T2DM subjects raises the concern whether CV complications are due to augmented levels of plasma sPRR. To test the hypothesis that increased plasma sPRR is associated with systemic RAS activation, CV complications, and decline in renal function, we measured plasma sPRR, plasma renin activity (PRA), and biomarkers of renal dysfunction in 269 patients (mean age, 48 ± 1 years; 42% men, 58% women), including 173 controls (CT) and 96 patients with T2DM. Plasma sPRR levels measured by ELISA were higher in T2DM patients (19.2 ± 7.6 ng/mL) compared with CT (16.5 ± 0.4 ng/mL; p<0.001). Plasma levels of sPRR contrasted between T2DM and CT patients of same sex (Women: 20 ± 1.11 vs. 15.3 ± 0.3 ng/mL; p<0.001; Men: 17 ± 1 vs. 18 ± 0.5 ng/mL; p=0.18). PRA was augmented in T2DM patients, including Men: 9.8 ± 3,6 vs. Ang I/mL/hr; p<0.001, and even greater in Women: 13.5 ± 1.1 vs. 3.1 ± 0.3 Ang I/mL/hr; p<0.001. Increases in sPRR and PRA paralleled with hypertension, declined eGFR, and albumin/creatinine ratio in T2DM patients. Interestingly, PRA was positively correlated with plasma sPRR in women (r=0.49; p<0.001) but not in men (r=0.15 1; p=0.207). Multiple regression analysis, adjusted by age, BMI, and groups supports the association between plasma sPRR and T2DM status in women (p<0.001) but not in men. In conclusion: 1) Plasma sPRR is associated with PRA in T2DM women but not in men; and 2) The association between sPRR and PRA predisposes women with T2DM to systemic RAS activation and CV complications, as hypertension and CKD. Plasma sPRR reflects systemic RAS activation and has the potential to be a biomarker of T2DM and CV complications, particularly in women.