RELATIONSHIP OF OXIDATIVE STRESS TO URINARY ANGIOTENSIN CONVERTING ENZYME 2 IN TYPE 2 DIABETES MELLITUS PATIENTS.

Abstract

Angiotensin converting enzyme 2 (ACE2) is highly expressed in the kidney and cleaves angiotensin II to Angiotensin (1-7), annihilating the deleterious effects of angiotensin II which is known to be a strong activator of oxidative stress. We aimed to evaluate the relationship of oxidative stress to urinary ACE2 (uACE2) in type 2 diabetes mellitus (T2DM) patients. We included consecutive normo or microalbuminuric T2DM patients in an observational transversal study. Routine laboratory investigations, plasma malondialdehyde (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 method) as two measures of serum antioxidant capacity and uACE2 (ELISA method) were assessed. MDA showed a negative correlation with SOD (r=-0.44, p=0.001), CAT (r=-0.37, p=0.006), uACE2 (r=-0.33, p=0.016) and a positive correlation with glycated haemoglobin (HbA1c) (r=0.49, p<0.001) and associated cardiovascular disease (r=0.42, p=0.001). CAT as also positively correlated to uACE2 (r=0.29, p=0.037). SOD was also negatively correlated with glycemia (r=-0.71, p<0.001) and HbA1c (r=-0.53, p<0.001). 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 (p<0.001). In multivariate logistic regression uACE2 was the only predictor for MDA above or below its median (OR=0.94, 95%CI[0.90-0.98], p=0.002). Increased prooxidant serum capacity is associated with lower uACE2 levels in T2DM patients.