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. 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. 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. 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.

中文翻译：

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2型糖尿病患者可溶性肾素原受体的性别差异


可溶性肾素原受体 (sPRR) 是肾素-血管紧张素系统 (RAS) 的成员，在先兆子痫、高血压、慢性肾病 (CKD) 和 2 型糖尿病患者的血浆中升高。我们的目标是检查 sPRR 和 RAS 激活之间的关系，以确定 sPRR 的性别二态性是否可以解释 2 型糖尿病患者肾脏结局的性别差异。该研究纳入了 269 名参与者（平均年龄 48 ± 16 岁；42% 男性，58% 女性），其中包括 173 名对照者和 96 名 2 型糖尿病受试者。在血浆和尿液中，我们测量了 sPRR、血浆肾素活性 (PRA) 和肾素原。在尿液中，我们还测量了血管紧张素原以及肾功能障碍的其他生物标志物。与男性相比，2 型糖尿病女性患者的血浆 sPRR 和 PRA 显着更高。在这些女性中，血浆 sPRR 与 PRA、年龄和体重指数 (BMI) 呈正相关。相反，在男性中，尿液中的 sPRR 与尿液中的 eGFR 呈正相关，但与尿液中的 eGFR 不呈正相关，但与尿液中的肾素活性、血浆葡萄糖、年龄和 BMI 呈负相关。在 2 型糖尿病患者中，sPRR 以性别依赖性方式促进 RAS 刺激。在患有糖尿病的女性中，血浆 sPRR 的增加与全身 RAS 的激活同时发生。而在糖尿病男性中，尿液中 sPRR 的降低与肾内 RAS 刺激相匹配。 sPRR 可能是 2 型糖尿病男性和女性肾内 RAS 激活和肾功能障碍的潜在指标。