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(Pro)renin receptor[(P)RR] binds to renin and its precursor prorenin to activate tissue renin-angiotensin system (RAS). (P)RR is cleaved by furin to generate soluble (P)RR [s(P)RR], which is secreted into the extracellular space, and ATP6AP2 protein, which is an accessory protein of vacuolar-type H+-ATPase (V-ATPase) and plays an essential role in controlling intracellular vesicular acid environment. It has been reported that (P)RR may have a role in transporting H+ to the urine in the collecting duct. Although blood s(P)RR level has been recognized as a biomarker reflecting the status of tissue RAS, the significance of urinary s(P)RR excretion has not been determined. Therefore, the present study was undertaken to investigate the characteristics of urinary s(P)RR excretion.

Design and Method:

Urinary s(P)RR excretion was measured by ELISA and relationships between urinary s(P)RR excretion and background factors were investigated in 126 (58 males, 51 ± 16 y.o) subjects. Relationships between changes in urine pH and urinary s(P)RR excretion by treatment with vitamin C, which reduces urine pH, for 14 days were investigated.


The mean urinary s(P)RR excretion was 2.32 ± 3.77 ng/gCre. Urinary s(P)RR excretion was significantly positively and negatively related with urine pH (r = 0.376, p < 0.001) and uric acid (r = -0.237, p = 0.026), respectively. Multiple regression analysis testing urine pH, eGFR, uric acid, and serum s(P)RR, as independent variables revealed that only urine pH was significantly positively associated with urine s(P)RR excretion. Changes in urine pH and urinary s(P)RR excretion by vitamin C treatment were significantly positively related (r = 0.899, p = 0.015).


Urinary s(P)RR excretion showed an independent association with urine pH. It can be speculated that urine (P)RR excretion is elevated due to increased (P)RR expression in tubules resulting from V-ATPase activation to compensate decreased urine pH, although this presumption needs to be estimated by further investigations.

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