Abstract

Objective: Cardiovascular (CV) events are the leading cause of death in patients with chronic kidney disease (CKD). Endothelial dysfunction (ED) is a predictor of CV events and functional assessment of the endothelium can identify early endothelial damage and predict CV risk. Renalase is a newly-described circulating oxidase endowed with hypotensive and cardioprotective effects, which is mainly expressed in kidney but also in heart and endothelium. The aim of this study was to assess associations between renalase plasma levels, renal function, biomarkers of CV risk and endothelial dysfunction in 64 pre-dialysis CKD patients, stages 1 to 5, followed up in our outpatient clinic. Design and method: Charlson Index, renal function (eGFR), phosphate (Pi), parathormone (iPTH) and natriuretic peptide type B (BNP) serum levels were assessed using standard laboratory methods. Endothelial function (RHI) was evaluated by peripheral arterial tonometry (Endo-Pat 2000). Intact FGF-23 blood levels were measured by ELISA from Immutopics, Inc. Plasma renalase levels were assessed using a commercially ELISA kit from Uscn Life Science Inc. We examined 64 (35F:29 M) CKD patients, with mean age of 60 ± 2 years, and mean eGFR: 49.7 ± 4 ml/min/1,73m2. The most frequent cause of CKD (15.6%) was diabetic nephropathy and mean Charlson index was 4.7 ± 0.4. Results: In univariate analysis, renalase serum levels negatively correlated with eGFR (r = -0.84, p < 0.0001) and RHI (r = -0.36, p < 0.03), and positively correlated with age (r = 0.40, p < 0.05), Charlson Index (r = 0.60, p < 0.0001), Pi serum levels (r = 0.57, p < 0.0005), FGF-23 (r = 0.44, p < 0.01), iPTH (r = 0.76, p < 0.001) and BNP (r = 0.64, p < 0.05). In adjusted analysis the increase in renalase plasma levels was only significantly correlated with the decrease of eGFR (β=-0.31, p < 0.05). This relationship proved to be independent of changes in age, Charlson Index, RHI, FGF-23, serum Pi and iPTH. Conclusions: The increase in plasma renalase levels observed in CKD patients is primarily dependent on renal function. It remains to be established whether or not renalase plasma levels are associated with increased of CV risk in CKD.

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