Sex differences in soluble prorenin receptor in patients with type 2 diabetes

Bruna Visniauskas,Danielle Y Arita,Andrew C Curnow,John J Lefante,Mohammed A Feroz,Edgar A Jaimes,Michael J Accavitti,Franck Mauvais-Jarvis,Vivian A Fonseca,Jennifer Hong,Carla B Rosales,Tina K Thethi,Minolfa C Prieto,Gabrielle Dawkins,Christina Luffman

doi:10.1186/s13293-021-00374-3

Abstract

BackgroundThe soluble prorenin receptor (sPRR), a member of the renin-angiotensin system (RAS), is elevated in plasma of patients with preeclampsia, hypertension, chronic kidney disease (CKD), and type 2 diabetes. Our goal was to examine the relationship between sPRR and RAS activation to define whether sexual dimorphisms in sPRR might explain sex disparities in renal outcomes in patients with type 2 diabetes.MethodsTwo hundred sixty-nine participants were included in the study (mean age, 48 ± 16 years; 42% men, 58% women), including 173 controls and 96 subjects with type 2 diabetes. In plasma and urine, we measured sPRR, plasma renin activity (PRA), and prorenin. In the urine, we also measured angiotensinogen along with other biomarkers of renal dysfunction.ResultsPlasma sPRR and PRA were significantly higher in women with type 2 diabetes compared to men. In these women, plasma sPRR was positively correlated with PRA, age, and body mass index (BMI). In contrast, in men the sPRR in urine but not in plasma positively correlated with eGFR in urine, but negatively correlated with urine renin activity, plasma glucose, age, and BMI.ConclusionsIn patients with type 2 diabetes, sPRR contributes to RAS stimulation in a sex-dependent fashion. In diabetic women, increased plasma sPRR parallels the activation of systemic RAS; while in diabetic men, decreased sPRR in urine matches intrarenal RAS stimulation. sPRR might be a potential indicator of intrarenal RAS activation and renal dysfunction in men and women with type 2 diabetes.

Highlights

Type 2 diabetes mellitus is a major risk factor for cardiovascular (CV) and renal diseases [1]
We found a significant association between estimated glomerular filtration rate (eGFR), plasma and urine soluble prorenin receptor (sPRR), urine renin activity, and age, race, and anti-hypertensive
Our results indicated that in patients with type 2 diabetes, urine renin activity increased as the concurrence of diabetes status, hypertension, eGFR < 60 mL/min per 1.73 m2, and/or albumin to creatinine ratio (ACR) increased (Supplemental, Figure S1)

Summary

Introduction

Type 2 diabetes mellitus is a major risk factor for cardiovascular (CV) and renal diseases [1]. A high percentage of patients with type 2 diabetes exhibit inappropriate activation of systemic and intrarenal renin-angiotensin systems (RAS) [2], which increases the risk of acute. The levels of sPRR are increased in the plasma of patients with essential hypertension, preeclampsia, gestational diabetes, obstructive sleep apnea, DN, and CKD [19,20,21,22]. The soluble prorenin receptor (sPRR), a member of the renin-angiotensin system (RAS), is elevated in plasma of patients with preeclampsia, hypertension, chronic kidney disease (CKD), and type 2 diabetes. Our goal was to examine the relationship between sPRR and RAS activation to define whether sexual dimorphisms in sPRR might explain sex disparities in renal outcomes in patients with type 2 diabetes

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