Expression of ACE and ACE2 in individuals with diabetic kidney disease and healthy controls.

Mizuiri, Sonoo; Hemmi, Hiromichi; Arita, Michitsune; Ohashi, Yasushi; Tanaka, Yoshihide; Miyagi, Moriatsu; Sakai, Ken; Ishikawa, Yukio; Shibuya, Kazutoshi; Hase, Hiroki; Aikawa, Atsushi

BACKGROUND Angiotensin-converting enzyme (ACE) 2 (ACE2) is expressed mainly in the heart and kidney and forms angiotensin-1-7 from angiotensin II. ACE2 might act in a counterregulatory manner to ACE. There is little information about renal ACE and ACE2 expression in human diabetic nephropathy. STUDY DESIGN Cross-sectional study. SETTING & PARTICIPANTS Kidney tissue from 20 patients with type 2 diabetes and overt nephropathy and 20 healthy kidney donors. PREDICTOR Diabetes status. OUTCOMES & MEASUREMENTS Renal expression of ACE and ACE2 assessed by means of immunohistochemistry and in situ hybridization. Correlation between ACE and ACE2 expression and levels of various biochemical parameters. RESULTS Decreased ACE2 and increased ACE expression in both the tubulointerstitium and glomeruli resulted in a significant (P < 0.001) increase in ACE/ACE2 ratio in patients with diabetes with overt nephropathy compared with controls, although ACE messenger RNA in the tubulointerstitium did not significantly increase. ACE/ACE2 ratio correlated positively with values for mean blood pressure, fasting blood glucose, serum creatinine, proteinuria, and hemoglobin A(1c) and inversely with estimated glomerular filtration rate (P < 0.001). LIMITATIONS Inclusion of small number of human renal biopsy specimens with structural distortion of cortical tissue. CONCLUSIONS The high ACE/ACE2 ratio in kidneys of patients with type 2 diabetes with overt nephropathy may contribute to renal injury.