Association between serum soluble (pro)renin receptor level and lower limb amputation in hemodialysis patients

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Abstract Background The (pro)renin receptor [(P)RR] is a multifunctional protein, and its soluble form [s(P)RR], generated by proteolytic cleavage, has been proposed as a biomarker reflecting tissue renin–angiotensin system activity. Patients on maintenance hemodialysis (HD) have a high burden of cardiovascular disease driven by accelerated atherosclerosis. Serum s(P)RR levels are associated with atherosclerosis progression independently of conventional risk factors, suggesting its potential as a novel cardiovascular biomarker in this population. Herein, we investigated the association between s(P)RR and lower limb amputation in patients undergoing HD. Methods Serum s(P)RR levels were measured before and after amputation in 11 patients. (P)RR immunostaining was performed on amputated tissues to assess the local expression. Furthermore, serum s(P)RR levels were compared between 27 patients on HD who underwent lower limb amputation (amputation group) and 250 patients on HD without a history of amputation (control group). Results Although elevated s(P)RR levels were observed in patients on HD who underwent lower limb amputation, no evident (P)RR expression was detected in the amputated tissues, and serum s(P)RR levels showed no significant changes before and after amputation. Moreover, the association between serum s(P)RR levels and limb amputation remained significant after adjusting for atherosclerotic progression factors other than C-reactive protein (CRP) but disappeared when adjusted for CRP. Conclusions These findings suggest that chronic inflammation plays a role in the relationship between lower limb amputation and elevated serum s(P)RR levels.