ACE I/D Polymorphism, Plasma ACE Levels, and Long-term Kidney Outcomes or All-Cause Death in Patients With Type 1 Diabetes.

OBJECTIVE
The deletion (D) allele of the ACE insertion/deletion (I/D) polymorphism is a risk
factor for diabetic kidney disease. We assessed its contribution to long-term kidney
outcomes and all-cause death in patients with long-standing type 1 diabetes.
RESEARCH DESIGN AND METHODS
A total of 1,155 participants from three French and Belgian cohorts were monitored
for a median duration of 14 (interquartile range, 13) years. The primary outcome
was the occurrence of end-stage kidney disease (ESKD) or a 40% drop in the
estimated glomerular filtration rate (eGFR). Secondary outcomes were the individual
components of the primary outcome, rapid decline in eGFR (steeper than
–3 mL/min/1.73 m2 per year), incident albuminuria, all-cause death, and a composite
ESKD or all-cause death. Hazard ratios (HRs) for XD versus II genotype and
for baseline plasma ACE levels were computed by Cox analysis. Genotype performance
in stratifying the primary outcome was tested.
RESULTS
Genotype distribution was 954 XD and 201 II. The primary outcome occurred in
20% of XD and 13% of II carriers: adjusted HR 2.07 (95% CI 1.32–3.40; P 5 0.001).
Significant associations were also observed for rapid decline in eGFR, incident albuminuria,
ESKD, all-cause death, and ESKD or all-cause death. Baseline plasma
ACE levels were higher in XD carriers and significantly associated with an
increased risk of the primary outcome. The ACE genotype enhanced net reclassification
improvement (0.154, 95% CI 0.007–0.279; P 5 0.04) and integrated discrimination
improvement (0.012, 95%CI 0.001–0.021; P 5 0.02) for primary
outcome stratification.
CONCLUSIONS
The D-allele of the ACE I/D polymorphism was associated with an increased risk
of major kidney events and all-cause death in patients with long-standing type 1
diabetes.