Division of Nephrology, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan.
Ninomiya Central Clinic, Tochigi, Japan.
Clin Exp Nephrol. 2011 Jun;15(3):398-404. doi: 10.1007/s10157-010-0398-5. Epub 2011 Jan 15.
Circulating prorenin contributes to the pathogenesis of tissue damage leading to cardiovascular disease (CVD) in hypertension and diabetic mellitus (DM) by activating the tissue renin-angiotensin-aldosterone (RAS) system; however, little is known about its roles in hemodialysis (HD) patients.
We evaluated plasma prorenin level and prorenin receptor [(P)RR] expression in peripheral blood mononuclear cells (PBMCs) in 49 nondiabetic HD (non-DM-HD) patients. Then we investigated the association between plasma prorenin level or (P)RR expression level in PBMCs and CVD-predictive biomarkers.
The plasma prorenin level increased in non-DM-HD patients [147.1 ± 118.9 pg/ml (standard value <100 pg/ml)]. The (P)RR mRNA expression level in PBMCs also increased 1.41 ± 0.39-fold in non-DM-HD patients compared with that in healthy control subjects (p < 0.001). Although plasma prorenin level did not correlate with plasma BNP level and plasma high-sensitivity C-reactive protein level, it significantly correlated with plasma 8-hydroxydeoxyguanosine (8-OHdG) level (r = 0.535, p < 0.001). The plasma prorenin level did not correlate with plasma renin activity (PRA), plasma angiotensin I (AT I) level, plasma angiotensin II (AT II) level and plasma aldosterone (Ald) level. PRA, plasma AT I level, plasma AT II level and plasma Ald level did not correlate with the level of any CVD predictive biomarker. (P)RR expression level in PBMCs did not correlate with the level of any CVD predictive biomarker.
The plasma prorenin level and (P)RR expression level in PBMCs increased, and the plasma prorenin level was associated with plasma 8-OHdG level independent of circulating RAS in non-DM-HD patients.
循环前肾素通过激活组织肾素-血管紧张素-醛固酮（RAS）系统，导致高血压和糖尿病（DM）患者的组织损伤，从而导致心血管疾病（CVD）。然而，对于血液透析（HD）患者，其作用知之甚少。
我们评估了 49 例非糖尿病血液透析（非 DM-HD）患者外周血单个核细胞（PBMC）中的血浆前肾素水平和前肾素受体[（P）RR]表达。然后，我们研究了血浆前肾素水平或 PBMC 中（P）RR 表达水平与 CVD 预测生物标志物之间的关系。
非 DM-HD 患者的血浆前肾素水平升高[147.1±118.9pg/ml（标准值<100pg/ml）]。与健康对照组相比，非 DM-HD 患者 PBMC 中（P）RR mRNA 表达水平也增加了 1.41±0.39 倍（p<0.001）。尽管血浆前肾素水平与血浆 BNP 水平和血浆高敏 C 反应蛋白水平不相关，但与血浆 8-羟基脱氧鸟苷（8-OHdG）水平显著相关（r=0.535，p<0.001）。血浆前肾素水平与血浆肾素活性（PRA）、血浆血管紧张素 I（AT I）水平、血浆血管紧张素 II（AT II）水平和血浆醛固酮（Ald）水平不相关。PRA、血浆 AT I 水平、血浆 AT II 水平和血浆 Ald 水平与任何 CVD 预测生物标志物的水平均不相关。（P）RR 在 PBMC 中的表达水平与任何 CVD 预测生物标志物的水平均不相关。
非 DM-HD 患者的血浆前肾素水平和 PBMC 中（P）RR 表达水平升高，且血浆前肾素水平与循环 RAS 无关，与血浆 8-OHdG 水平相关。
