Deletion insertion polymorphism of the angiotensin converting enzyme gene and progression of diabetic nephropathy.

BACKGROUND: The activity in the renin angiotensin system is important for the progression of diabetic nephropathy. Genetic abnormalities in this system have been suggested as a risk factor for the development and progression of diabetic nephropathy. The homozygous DD (deletion) genotype of the angiotensin-converting enzyme gene has been associated with increased circulating angiotensin converting enzyme and a more rapid progression of IgA nephritis. The aim of the present study was to investigate the relationship between the DD genotype and rate of decline in kidney function in patients with type 1 diabetes and nephropathy in relation to other risk factors for loss of renal function.

METHODS: The insertion-deletion polymorphism was determined in patients with type 1 diabetes mellitus and diabetic nephropathy. Retrospective data were collected in 86 patients. The patients were studied by determining glomerular filtration rate during a mean (+/-SD) of 8.5 +/- 4.0 years (range 1.3-14.5 years) using the clearance of 51Cr EDTA. Measurements for glycaemic control, urinary albumin excretion, blood pressure, and serum lipids were available for the study period.

RESULTS: The mean decline in glomerular filtration rate was 3.2 +/- 3.6 ml/min/year in all patients. Patients with the DD, ID and II genotype showed a rate of change in glomerular filtration of -3.5 +/- 3.5, -3.1 +/- 4.4 and -2.6 +/- 2.3 ml/min/year respectively. The tendency towards a more rapid decline in kidney function in the DD genotype was nonsignificant. The decline in renal function was significantly correlated to systolic and diastolic blood pressure, Hb AIc and serum triglycerides. Serum cholesterol was nearly significantly correlated to the decline in glomerular filtration rate (P = 0.057). Of these variables, glycaemic control and blood pressure control remained significant in multivariate analysis (P = 0.02 and P = 0.04, respectively). The patients with the DD genotype weighted significantly less. The body weight in patients with the DD genotype was 67.1 +/- 11.4 kg vs 74.9 +/- 9.2 kg in patients with the II genotype (P = 0.018).

CONCLUSION: In this study, poor glycaemic and blood pressure control were associated with a more rapid loss of renal function in diabetic nephropathy while polymorphism of the angiotensin converting enzyme gene was not.