The (pro)renin receptor ((P)RR) is expressed in several tissues including kidney, heart and brain, and is thought to regulate the tissue renin–angiotensin system (RAS) through the non-proteolytic activation of prorenin. (P)RR is cleaved by furin to generate soluble (P)RR (s(P)RR), which is secreted into the extracellular space. s(P)RR is a candidate biomarker reflecting the status of the tissue RAS. Here, we investigated the relationship between background factors and serum s(P)RR levels. We measured s(P)RR levels in 122 patients with essential hypertension (EH) and assessed the relationships between background factors and s(P)RR levels. Serum s(P)RR levels were 19.0 ± 4.9 ng ml−1. Single regression analyses showed that age (r =0.251, P<0.01), serum creatinine levels (r =0.229, P<0.05) and urinary angiotensinogen excretion (r =0.196, P<0.05) were positively correlated with s(P)RR levels, whereas estimated glomerular filtration rate (eGFR; r = −0.337, P<0.001) were negatively correlated. Multiple regression analyses of age, blood pressure (BP), hemoglobin A1c (HbA1c) and s(P)RR levels revealed that age and s(P)RR levels were negatively correlated with the eGFR (P<0.05). In patients with EH, serum s(P)RR levels correlated positively with renal function independent of age, BP and HbA1c. These findings support s(P)RR as a useful biomarker that reflects the status of the tissue RAS.

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To examine the involvement of (pro)renin receptor in the accelerated organ damage in streptozotocin-induced diabetic male SHRsp, the rats fed a high-salt diet were divided into 5 groups: a group treated with the vehicle, a group treated with 15 mg/kg/day of imidapril (ACEi), a group treated with 60 mg/kg/day of imidapril (High ACEi), a group treated with handle region peptide (HRP), and a group treated with both ACEi and HRP (ACEi+HRP). After 8 weeks, the arterial pressure was similar in the vehicle and HRP groups and decreased in the ACEi-treated groups. The renal angiotensin II content decreased similarly in the groups treated with ACEi and/or HRP. Urinary protein excretion also decreased in the ACEi, High ACEi, and HRP groups and significantly further decreased in the ACEi+HRP group. The heart weight of the ACEi+HRP group was significantly lower than that of any other groups, although the cardiac angiotensin II levels decreased similarly in the groups treated with ACEi and/or HRP. Thus, (pro)renin receptor contributes to the accelerated pathogenesis in the heart and kidneys of diabetic SHRsp.

The (pro)renin receptor is important in the regulation of the tissue renin-angiotensin-aldosterone system. The benefits and safety of single-aliskiren treatment without other renin-angiotensin-aldosterone system inhibitors remain unclear. The serum level of the soluble form of the (pro)renin receptor is thought to be a biomarker reflecting the activity of the tissue renin-angiotensin-aldosterone system. We investigated the effects of single renin-angiotensin-aldosterone system blockade with aliskiren on renal and vascular functions and determined if serum level of the soluble (pro)renin receptor was a predictor of aliskiren efficacy in hypertensive patients with chronic kidney disease. Thirty-nine essential hypertensive patients with chronic kidney disease in our outpatient clinic were randomly assigned to receive either aliskiren or amlodipine. The parameters associated with renal and vascular functions and indices of renin-angiotensin-aldosterone system components, including serum levels of the soluble form, were evaluated before and after 12-week and 24-week treatment. Blood pressure was not significantly different between the groups. No significant changes in serum levels were observed in the soluble (pro)renin receptor in either group. Urinary albumin, protein excretion, and cardio-ankle vascular index significantly decreased in the aliskiren group. In the aliskiren group, there was a significant negative correlation between the basal level of the soluble (pro)renin receptor and the change in plasma aldosterone concentration. Single renin-angiotensin-aldosterone system blockade with aliskiren showed renal and vascular protective effects independent of blood pressure reduction. Serum levels of the soluble (pro)renin receptor may indicate aldosterone production via the (pro)renin receptor in the adrenal gland.

Objective The management of blood pressure (BP) in hypertensive patients is the key to preventing a progression of organ damage. The brachial BP (bBP) has been used as the representative method for measuring the BP. The central BP (cBP), which is, different from the bBP due to the propagation and the reflection of the pulse wave in the arterial system, has recently received attention because it can now be estimated noninvasively. We examined the relationships between the difference in the central systolic BP (csBP) and the brachial systolic BP (bsBP) (Δ) and other factors in hypertensive patients. Methods The bsBP and csBP were measured in patients with essential hypertension and the relationships between the bsBP, csBP, or Δ and background factors including age, the brain natriuretic peptide (BNP) level, the estimated glomerular filtration rate (eGFR), flow-mediated vasodilation (an index of vascular endothelial function), the cardio-ankle vascular index (CAVI, an index of arteriosclerosis), and the carotid intima-media thickness (an index of atherosis) were investigated. Results The data of 191 patients were analyzed. Although there was no significant correlation between the CAVI and the bsBP; positive correlations were observed between the CAVI and the csBP (r=0.249, p=0.001). The Δ value showed significant positive correlations with age, and the BNP, eGFR, and CAVI values. Conclusion The csBP is more strongly associated with arteriosclerosis than the bsBP. Moreover, the Δ value is more strongly associated with cardiac function, renal function, and arteriosclerosis than the bsBP or csBP. These data suggested that the Δ value may have a greater prognostic value than the bsBP or csBP and may be worth calculating in the clinical setting.