SP392RELATIONSHIP OF OXIDATIVE STRESS TO URINARY ANGIOTENSIN COVERTING ENZYNE 2 IN TYPE 2DIABETES PATIENTS

Abstract

Introduction and Aims: Angiotensin converting enzyme 2 (ACE2) is highly expressed in the kidney and cleaves angiotensin II to Angiotensin-(1-7), thus annihilating the deleterious effects of angiotensin II which is known to be a strong activator of oxidative stress. The purpose of the present study was to evaluate for the first time to our knowledge the relationship of oxidative stress to urinary ACE2 in type 2 diabetes patients with incipient diabetic kidney disease. Methods: We conducted a transversal evaluation of type 2 diabetes patients. Patients with urinary albumin to creatinine ratio (uACR) > 300mg/g creatinine were excluded from the study. Routine laboratory investigations, uACE2 (ELISA method), serum malondyaldehyde (MDA, fluorimetric thiobarbituric method) as a marker of prooxidant capacity and superoxide dismutase (SOD, cytochrome reduction method) and catalase (CAT) activity (in erythrocyte lysate by the modification of absorbance at 240nm) as two measures of serum antioxidant capacity were assessed. Results: Fifty-three patients were included with their mean estimated glomerular filtration rate (eGFR-CKD EPI) of 89.3 (67.86-99.5) ml/min/1.73m2 and mean uACR of 15.36 (4.35-36.02)mg/g creatinine. MDA showed a negative correlation with SOD (r=-0.44, p=0.001), CAT (r=-0.37, p=0.006), urinary ACE2 (r=-0.33, p=0.016) and systolic blood pressure (SBP) (r=-0.28, p=0.039) and a positive correlation with HbA1c (r=0.49, p<0.001). Except for the correlation with MDA, SOD was negatively correlated with glycemia (r=-0.71, p<0.001), HbA1c (r=-0.53, p<0.001) and positively correlated with SBP (r=0.29, p=0.038). Except for the correlation with MDA, CAT was positively correlated to urinary ACE2 (r=0.29, p=0.037). Patients with lower MDA (when divided according to median value of 3.88 nmol/ml had higher uACE2 57.15 (40.3-71.2) pg/ml compared to 38.5 (31.8-45.95)pg/ml in patients with higher MDA. In our patients urinary ACE2 level of 49.2pg/ml was the cutoff (ROC curve) according to MDA (p=0.018). In multivariate logistic regression (stepwise model) with urinary ACE2 as dependent variable (less than 49.2 pg/ml vs. higher than 49.2 pg/ml) and all the other variable as independent, only MDA (OR=0.66, 95%CI (0.45-0.99), p=0.044) and gender (OR=4.42, 95%CI (1.16-16.85), p=0.03) were significant predictors for urinary ACE2. Conclusions: Increased prooxidant serum capacity is the main predictor of urinary ACE2.