Journal
BIOLOGY OF SEX DIFFERENCES
Volume 12, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s13293-021-00374-3
Keywords
Plasma renin activity; Urine renin activity; eGFR; Urine angiotensinogen; Sexual dimorphism
Categories
Funding
- National Institute of Diabetes and Digestive and Kidney (NIDDK) [RO1-DK104375]
- Tulane SOM Faculty Research Pilot Funds Program from the National Center for Advancing Translational Sciences of the UAB-CCTS Partner Network Multidisciplinary Pilot Program [UL1TR003096]
- Tulane SOM Faculty Pilot Fund
- Eunice Kennedy Shriver National Institute of Child Health & Human Development of the Building Interdisciplinary Research Careers in Women's Health (BIRCWH) Program [K12HD043451]
- TullisTulane Alumni Chair in Diabetes for VAF
- National Institute of General Medical Sciences - Louisiana Clinical and Translational Science, LACaTs [U54 GM104940]
- NIDDK awards [R01-DK074970, R01-DK107444]
- Department of Veterans Affairs Merit Review Award [BX003725]
- Tulane Center of Excellence in Sex-Based Biology Medicine
- National Cancer Institute
- NIDDK [RO1-DK114321]
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) from Brazil
- MD Student Endowed Fund Award
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The study revealed that there are differences in the expression levels of sPRR between men and women with type 2 diabetes, which may be related to the role of sex hormones in RAS activation.
Background 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. Methods Two 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. Results Plasma 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. Conclusions In 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.
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