Evaluation of risk factors for the development of nephropathy in patients with IDDM: insertion/deletion angiotensin converting enzyme gene polymorphism, hypertension and metabolic control.

Diabetic nephropathy represents a major complication in patients with insulin-dependent diabetes mellitus (IDDM). Intervention trials using angiotensin-converting enzyme (ACE) inhibitors have pointed towards the important pathogenetic role of the renin-angiotensin system. Recently an insertion/ deletion (I/D) polymorphism for the gene encoding the ACE has been described, the deletion type being associated with higher plasma ACE levels. As the intrarenal renin-angiotensin system might also be activated in this setting, we determined the ACE genotype together with other risk factors for the development of diabetic nephropathy in 122 patients with IDDM from a single centre with (n = 63) and without (n = 59) nephropathy. Long-term glycaemic control was evaluated using mean HbA1c values from the last 10 years. The two patient group were comparable with regard to duration of diabetes and glycaemic control as assessed by current HbA1c values. However, mean long-term HbA1c values were significantly higher in patients with diabetic nephropathy as was systemic blood pressure. The DD genotype was more prevalent in patients with renal disease. In the subgroup of patients who had had diabetes for more than 20 years (n = 90), the DD genotype was even more frequent in patients with nephropathy, and blood pressure and long-term HbA1c values were also higher in patients with renal disease. Logistic regression analysis revealed long-term glycaemic control, blood pressure and the ACE genotype to be independent risk factors for the prevalence of diabetic nephropathy.

Angiotensin-converting enzyme polymorphism in patients with terminal renal failure.

An insertion/deletion polymorphism has been described for the gene that encodes the angiotensin-converting enzyme. The deletion allele is associated with higher angiotensin-converting enzyme plasma levels, which ultimately might lead to increased angiotensin II concentrations. Because angiotensin II is a mediator for progressive renal injury, this study determined the frequency of distribution of the angiotensin-converting enzyme insertion/deletion polymorphism in 106 hemodialysis patients and in a group of 95 healthy control patients. There was no difference between the two groups as far as the distribution of the insertion and deletion allele was concerned. Of the total hemodialysis population, 26.4% exhibited the deletion/deletion genotype, as compared with 37.9% of the healthy control population. Also, when patients with terminal renal failure as a result of glomerular disease were analyzed separately, the frequency of the deletion/deletion genotype was identical to that of the control group. Furthermore, the frequency of hypertension, coronary artery disease, left ventricular hypertrophy, and dilated cardiomyopathy, were analyzed according to the angiotensin-converting enzyme genotype, but the deletion allele could not be defined as a risk factor in the study's hemodialysis population. It was therefore concluded that the angiotensin-converting enzyme insertion/deletion polymorphism is not a major risk factor for development of end-stage renal failure. Additionally, in hemodialysis patients, there is no association between the risk for cardiovascular diseases and the angiotensin-converting enzyme genotype.