Purpose: Podocyte lesion is recently recognized as an early event in diabetic kidney disease (DKD) and is reflected by urinary (u) nephrin (Neph) shedding. Angiotensin II plays an important role in podocyte dysfunction of diabetes. Angiotensin converting enzyme 2 (ACE2) is the main ACE variant in podocytes and counteracts deleterious angiotensin II effects. We assessed for the first time the relation of uACE2 and uNeph in type 2 diabetes subjects.
Material and method: Seventy-five type 2 diabetes patients were included in a transversal study. History, clinical and laboratory data, urinary albumin-to-creatinine ratio (uACR), and ELISA determination of uNeph and uACE2 were obtained.
Results: uNeph was 349.00 ± 133.42 pg/ml, and uACE2 was 45.50 (36.35-62.60) pg/ml. uNeph correlated to uACE2 (r = 0.44, p < 0.001) and to uACR (r = 0.25, p = 0.032). In multivariate regression, introducing parameters that are known to be related to DKD, uACE2 (p < 0.0001), LDL cholesterol (p = 0.02) and glycated hemoglobin (p = 0.03) remained significant predictors of uNeph. Normoalbuminuric patients had lower uNeph than patients with uACR > 30 mg/g (325.50 ± 135.45 vs 391.03 ± 121.40 pg/ml, p = 0.04); they also had a tendency versus lower uACE2 [41.40 (34.30-60.65) vs 52.57 (37.95-69.85) pg/ml, p = 0.06]. A cutoff for uNeph of 451.6 pg/ml was derived from the ROC curve analysis; uACE2 was the main determinant for uNeph being above or below this cutoff-OR = 1.09; 95 %CI (1.04-1.15), p = 0.001. Patients taking blockers of the renin angiotensin system had similar uNeph and uACE2. uNeph and uACE2 were not influenced by renal function.
Conclusion: uNeph is significantly correlated to uACE2 and uACR in type 2 diabetes patients.
Keywords: Albuminuria; Podocyte; Type 2 diabetes; Urinary ACE2; Urinary nephrin.