Urinary angiotensin-converting enzyme 2 in patients with CKD

Aim: Angiotensin-converting enzyme 2 (ACE2) is a type I membrane protein that antagonizes the action of angiotensin II. Because of the need for invasive kidney biopsy, little is known about the role of renal ACE2 in human kidney diseases. The authors studied if urinary ACE2 could provide a novel clue to renal ACE2 in chronic kidney disease (CKD). Methods: Subjects were 190 patients with CKD including 38 patients with diabetic nephropathy and 36 healthy subjects. Parameters were urinary ACE2 by enzyme-linked immunosorbent assay, blood pressure, casual plasma glucose, proteinuria, microalbuminuria, serum creatinine and estimated glomerular filtration rate. Urine and serum samples were also subjected to western blotting of ACE2. Results: Western blotting confirmed increased urinary ACE2 levels in patients with CKD. Urinary ACE2 was significantly higher in patients with CKD than healthy subjects (median 9.64 (interquartile range, 4.41-16.89) vs 1.50 (0.40-2.33) mg/g.creatinine, P < 0.001) and in patients with diabetic nephropathy than patients without diabetic nephropathy (median 13.16 (interquartile range 6.81-18.70) vs 8.90 (4.19-16.67) mg/g.creatinine, P < 0.05). No significant difference in urinary ACE2 was observed by the use of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker. Conclusion: Urinary ACE2 could be used as a non-invasive marker to understand the role of renal ACE2 in CKD.