EFFECT OF DELETION POLYMORPHISM OF ANGIOTENSIN-CONVERTING ENZYME GENEON PROGRESSION OF DIABETIC NEPHROPATHY DURING INHIBITION OF ANGIOTENSIN-CONVERTING ENZYME - OBSERVATIONAL FOLLOW-UP-STUDY

Objective-To evaluate the concept that an insertion/deletion polymorph ism of the angiotensin converting enzyme gene predicts the therapeutic efficacy of inhibition of angiotensin converting enzyme on progressio n of diabetic nephropathy. Design-Observational follow up study of pat ients with insulin dependent diabetes and nephropathy who had been tre ated with captopril for a median of 7 years (range 3-9 years). Setting -Outpatient diabetic clinic in a tertiary referral centre. Patients-35 patients with insulin dependent diabetes and nephropathy were investi gated during captopril treatment (median 75 mg/day (range 12.5 to 150 mg/day)) that was in many cases combined with a loop diuretic. 11 pati ents were homozygous for the deletion allele and 24 were heterozygous or homozygous for the insertion allele of the angiotensin converting e nzyme gene. Main outcome measures-Albuminuria, arterial blood pressure , and glomerular filtration rate according to insertion/deletion polym orphism. Results-The two groups had comparable glomerular filtration r ate, albuminuria, blood pressure, and haemoglobin A,, concentration at baseline. Captopril induced nearly the same reduction in mean blood p ressure in the two groups-to 103 (SD 5) mm Hg in the group with the de letion and 102 (8) mm Hg in the group with the insertion-and in geomet ric mean albumin excretion-573 (antilog SE 1.3) mu g/min and 470 (1.2) mu g/min, respectively. The rate of decline in glomerular filtration rate (linear regression of all glomerular filtration rate measurements during antihypertensive treatment) was significantly steeper in the g roup homozygous for the double deletion allele than in the other group (mean 5.7 (3.7) ml/min/year and 2.6 (2.8) ml/min/year, respectively; P = 0.01). Multiple Linear regression analysis showed that haemoglobin A(1c) concentration, albuminuria, and the double deletion genotype in dependently influenced the sustained rate of decline in glomerular fil tration rate (R(2) (adjusted) = 0.51). Conclusion-The deletion polymor phism in the angiotensin converting enzyme gene reduces the long term beneficial effect of angiotensin converting enzyme inhibition on the p rogression of diabetic nephropathy in patients with insulin dependent diabetes.