Urinary mRNA expression of ACE and ACE2 in human type 2 diabetic nephropathy

Abstract

Aims/hypothesis: The interplay of ACE and type 2 ACE (ACE2) has been recognised as playing an important role in the tissue renin-angiotensin system within the kidney. In the present study, we measured urinary mRNA expression of ACE and ACE2 in patients with type 2 diabetic nephropathy.

Methods: We studied 50 patients with diabetic nephropathy: 26 were being treated by ACE inhibitor (ACEI) alone (ACEI group), the other 24 by ACEI and angiotensin-receptor blocker (ARB) (ACEI+ARB group). mRNA expression of ACE and ACE2 was measured by real-time quantitative RT-PCR at 0 and 12 weeks. All patients were then followed for 56 weeks.

Results: Proteinuria correlated significantly with urinary ACE (r=0.454, p=0.001) and ACE2 expression (r=0.651, p<0.001). Urinary ACE2 expression correlated with estimated GFR (r= -0.289, p=0.042). In the ACEI group, there was a significant inverse correlation between the rate of GFR decline and urinary ACE2 expression at baseline (r= -0.423, p=0.031) as well as at 12 weeks (r= -0.395, p=0.046). In contrast, there was no significant correlation between the rate of GFR decline and urinary ACE2 expression at baseline or at 12 weeks in the ACEI+ARB group. The rate of GFR decline did not correlate with the baseline urinary ACE expression of either group.

Conclusion/interpretation: There was a relationship between urinary mRNA expression of ACE2 and the degree of proteinuria. The physiological implication and possibility of clinical application of quantifying urinary ACE2 expression require further study.