HDCN Article Review/Hyperlink

Yoshida H, Kuriyama S, Atsumi Y, et al.

Angiotensin I converting enzyme gene polymorphism in non- insulin dependent diabetes mellitus

Kidney Int (Aug) 50:657-664 1996

It is known that only a minority (15-25%) of patients with NIDDM are at risk to develop ESRD. This study was designed to determine if the presence of the DD genotype of the ACE gene would predict progressive renal disease.

In this paper, 168 patients with NIDDM followed for over 10 years were divided into 2 groups: (1) stable renal function (n=96) (2) declining renal function (n=72), defined as a doubling of serum creatinine (to > 2 mg/dl) or development of ESRD. All patients were genotyped for the I/D (insertion/deletion) polymorphism of the ACE gene.

The frequency of the ACE DD genotype was 7.3% in Group 1 (similar to that in general Japanese population) but was 26.4% in Group 2 (p < 0.001). Among all 168 patients studied, renal survival rate was significantly lower in patients with the DD genotype than in those with the ID or II genotypes, despite similar age, sex, blood pressure, HbA1c, duration of diabetes, % of patients with retinopathy, and % of patients with albuminuria. In those Group 2 patients with the DD genotype, progression to ESRD occurred at a more rapid rate. Although the frequency of albuminuria was not higher in DD genotype patients, 95% of DD patients with albuminuria progressed to ESRD within 10 years of diagnosis of diabetes.

In NIDDM, the ACE DD genotype is a risk factor for progressive renal disease. Among patients with albuminuria and the DD genotype, almost all progress to ESRD.

Comment: This study adds to our burgeoning knowledge about ACE polymorphism and diabetic nephropathy. Patients with the DD genotype have higher serum ACE levels, a greater pressor response to infusion of angiotensin I, and a greater fall in serum ACE activity after ACE inhibition. It appears that although nephropathy may not be more common in the presence of the DD genotype (Schmidt et al., Diabetic nephropathy study group, Kidney Int 47: 1176-81, 1995), the DD genotype is predictive of progression to ESRD in those with nephropathy. ACE inhibitors may have preferentially beneficial effects in ACE DD patients. It should be noted that the frequency of the DD genotype is higher (about 25%) in Caucasian Americans than in the Japanese population. (David J. Leehey, M.D., Loyola University at Chicago)