Abstract
The (pro)renin receptor [(P)RR] binds to renin and its precursor prorenin to activate the tissue renin-angiotensin system. It is cleaved to generate soluble (P)RR and M8–9, a residual hydrophobic truncated protein. The (pro)renin receptor also functions as an intracellular accessory protein of vacuolar-type H+-ATPase, which plays an essential role in controlling the intracellular vesicular acid environment. Thus, in the kidney, (P)RR may play a role in transporting H+ to urine in the collecting duct. Although blood soluble (P)RR has been recognized as a biomarker reflecting the status of the tissue renin-angiotensin system and/or tissue (P)RR, the significance of urinary soluble (P)RR excretion has not been determined. Therefore, this study aimed to investigate the characteristics of urinary soluble (P)RR excretion. Urinary soluble (P)RR excretion was measured, and its association with background factors was investigated in 441 patients. Relationships between changes in urine pH due to vitamin C treatment, which reduce urine pH, and urinary soluble (P)RR excretion were investigated in 10 healthy volunteers. Urinary soluble (P)RR excretion was 1.46 (0.44–2.92) ng/gCre. Urine pH showed a significantly positive association with urinary soluble (P)RR excretion, independent of other factors. Changes in urine pH and urinary soluble (P)RR excretion due to vitamin C treatment were significantly and positively correlated (ρ = 0.8182, p = 0.0038). These data showed an association between urinary soluble (P)RR excretion and urine pH in humans, suggesting that (P)RR in the kidney might play a role in urine pH regulation.
Highlights
Therenin receptor [(P)RR], which consists of 350 amino acids with a single transmembrane domain and binds to renin and prorenin, is widely expressed in various tissues, including the heart, brain, and kidney [1]
Information was collected on sex, age, hypertension, body mass index (BMI), and waist circumference (WC)
S(P)RR could be detected in urine, and urinary s(P)RR excretion was significantly and positively correlated with urine pH, independent of other factors in humans
Summary
The (pro)renin receptor [(P)RR], which consists of 350 amino acids with a single transmembrane domain and binds to renin and prorenin, is widely expressed in various tissues, including the heart, brain, and kidney [1]. The binding of prorenin to the extracellular domain of the (P)RR induces non-proteolytic renin activation [2], which accelerates the conversion of angiotensinogen to angiotensin. This process plays a key role in regulating the tissue renin-angiotensin system (RAS) [1]. Visceral fat area (VFA) was estimated by the bioelectrical impedance analysis method using HDS-2000 DUALSCAN1 (Omron Healthcare Co., Kyoto, Japan) in the morning after a 12-h fast, as previously described [17]. Office blood pressure (BP) and pulse rate (PR) were measured with the patient in a sitting position after resting for at least 5 min using an automated sphygmomanometer
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