Department of Physiology, Tulane University School of Medicine, 1430 Tulane Avenue, SL39, New Orleans, LA, 70112, USA.
Department of Medicine, Endocrinology Division, Tulane University School of Medicine, New Orleans, LA, USA.
Biol Sex Differ. 2021 May 1;12(1):33. doi: 10.1186/s13293-021-00374-3.
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.
作为肾素-血管紧张素系统（RAS）的成员，可溶性肾素原受体（sPRR）在先兆子痫、高血压、慢性肾脏病（CKD）和 2 型糖尿病患者的血浆中升高。我们的目标是研究 sPRR 与 RAS 激活之间的关系，以确定 2 型糖尿病患者中 sPRR 的性别二态性是否可以解释肾脏结局的性别差异。
本研究纳入了 269 名参与者（平均年龄 48 ± 16 岁；42%为男性，58%为女性），包括 173 名对照者和 96 名 2 型糖尿病患者。我们在血浆和尿液中测量了 sPRR、血浆肾素活性（PRA）和原肾素。在尿液中，我们还测量了血管紧张素原以及其他肾功能障碍的生物标志物。
与男性 2 型糖尿病患者相比，女性 2 型糖尿病患者的血浆 sPRR 和 PRA 明显升高。在这些女性中，血浆 sPRR 与 PRA、年龄和体重指数（BMI）呈正相关。相比之下，在男性中，尿液中的 sPRR 而不是血浆中的 sPRR 与尿中 eGFR 呈正相关，与尿中肾素活性、血糖、年龄和 BMI 呈负相关。
在 2 型糖尿病患者中，sPRR 以依赖于性别的方式促进 RAS 刺激。在糖尿病女性中，血浆中 sPRR 的增加与全身 RAS 的激活平行；而在糖尿病男性中，尿液中 sPRR 的减少与肾内 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。
