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.