Yoshida H, Kuriyama S, Atsumi Y, et al.
Angiotensin I converting enzyme gene polymorphism in non-
insulin dependent diabetes mellitus
(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
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
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)