Abstract P146: Serum Soluble (Pro)Renin Receptor Levels in Patients Undergoing Hemodialysis

Abstract

Background: The (pro)renin receptor [(P)RR] plays an important role in regulating the tissue renin-angiotensin system (RAS) through the non-proteolytic activation of prorenin, the precursor of renin. (P)RR is cleaved by furin to generate soluble (P)RR [s(P)RR], which is secreted into the extracellular space, and serum s(P)RR has been reported to reflect the status of tissue RAS. Hemodialysis (HD) patients have poor prognosis due to increased prevalence of cardiovascular diseases resulting from severe atherosclerosis. It is speculated that activation of tissue RAS by (P)RR may be associated with this condition, it remains speculative. In the present study, we investigated the relationships between serum s(P)RR levels and background factors including indices of atherosclerosis in HD patients. Methods: Serum s(P)RR levels were measured in 258 maintenance HD patients and these values were compared with 25 subjects with normal renal function. Western blot analysis was done using HD waste water samples, and clearance of s(P)RR through the membrane of dialyzer was examined. Furthermore, relationships between serum s(P)RR levels and background factors were assessed in HD patients. Results: Serum s(P)RR levels were significantly higher in HD patients (30.4±6.1 ng/ml) than those in subjects with normal renal function (16.5±4.3, P<0.0001). s(P)RR was detected in HD waste water by Western blot analysis, and the clearance of s(P)RR and creatinine were 56.9±33.5 and 147.6±9.50 ml/min, respectively. Serum (P)RR levels were significantly higher in those with ankle-brachial index (ABI) of < 0.9, an indicator of severe stenosis or obstruction of lower limb arteries, than those of ≧0.9 (32.2±5.9 and 30.1±6.2 ng/ml, respectively; P<0.05). The association between low ABI and high serum s(P)RR levels were observed even after the correction with age, history of smoking, HbA1c, and LDL-C. Conclusions: Serum s(P)RR levels are significantly higher in HD patients when compared with subjects with normal renal function, although s(P)RR are dialyzed to some extent. High serum s(P)RR levels may be associated with atherosclerosis independent of other risk factors, suggesting that serum s(P)RR could be used as a marker for atherosclerotic condition in HD patients.