Objective: Among blacks, we have observed that diabetic nephropathy (DN) is a more frequent primary cause of end-stage renal disease (ESRD) in women (approximately 50%) than in men (< 20%). In this study, we consider the role of the angiotensin-converting enzyme (ACE) polymorphism in determining this gender discrepancy and its role in the course of DN.
Methods: ACE genotype (I = insertion, D = deletion) was determined in consecutive consenting patients with type 2 diabetes mellitus and DN. Charts were subsequently reviewed for renal survival and its determinants (end point: time to ESRD from first clinic visit).
Results: Fifty-four patients (46 blacks) who had DN and were pre-ESRD consented: II = 6, ID = 31, and DD = 17. The allele frequency for D was approximately . 61 versus .39 for the I allele and did not differ by gender. Renal disease at presentation to the renal clinic was significantly worse in II. Twenty-one patients reached ESRD (II = 4, ID = 13, DD = 4; chi2 not significant), but ACE genotype had no significant effect on renal survival. Initial serum creatinine and blood pressure over follow-up independently predicted renal survival. Among blacks reaching ESRD, the presence of the D allele was associated with higher blood pressures. Patients without a family history of diabetes (chi2, p = .01) or diabetic retinopathy (chi2, p = .02) were more likely to have the DD genotype.
Conclusions: The gender discrepancy observed in rates of ESRD owing to DN in blacks is not likely dependent on ACE genotype. The effects of ACE genotype on renal disease progression were not significant; however, patients with diabetic nephropathy and DD genotype were less likely to have traditional risk factors for diabetes or diabetic nephropathy.