Progression of microalbuminuria (defined as urinary albumin excretion rate (AER) of 30±300 mg/24h [1]) to overt diabetic nephropathy in patients with Type I (insulin-dependent) diabetes mellitus is retarded by treatment with inhibitors of angiotensin converting enzyme (ACE). Even at the microalbuminuric stage, pathologic changes are present in the kidney [2] together with widespread endothelial dysfunction [3] [4]. Microalbuminuria is associated with excess cardiac morbidity [5]. It may therefore be worthwile to identify diabetic patients at risk before the stage of microalbuminuria, to start preventive treatment. Several risk factors for progression to microalbuminuria have been proposed [6,7], such as poor metabolic control, hypertension and high-normal AER.The most attractive factors for identifying risk are those involved in the pathogenesis of the disease. The favourable response to ACE inhibitors [8,9] suggests that the renin angiotensin system is one which is supported by experimental evidence that angiotensin II (AngII) is an important factor in the pathogenesis Diabetologia (1999) Abstract Aims/hypothesis. The renin-angiotensin system is possibly involved in the pathogenesis of diabetic nephropathy. The most striking change in renin-angiotensin system components in blood of patients with diabetic nephropathy is an increased prorenin concentration. We investigated prospectively serum concentrations of renin-angiotensin system components and the time course of prorenin increase in normoalbuminuric diabetic patients developing microalbuminuria. Methods. Patients (n = 199) with Type I (insulin-dependent) diabetes mellitus and normoalbuminuria at baseline were prospectively followed for 10 years. The prorenin concentrations and other variables possibly associated with the occurrence of microalbuminuria, were investigated by Cox-regression analysis. Results. Of the patients 29 developed microalbuminuria. Glycated haemoglobin values were higher at baseline in these patients. Serum prorenin was similar at baseline but rose in the 29 patients before the development of microalbuminuria and was stable in patients with stable albumin excretion. Renin, angiotensinogen and angiotensin converting enzyme serum concentrations were stable in both groups. Prorenin and glycated haemoglobin were independent prognostic factors for the development of microalbuminuria. A prognostic index, based on these variables, was constructed to estimate the relative risk of developing microalbuminuria. Conclusions/interpretation. Increase in serum prorenin precedes onset of microalbuminuria in normotensive patients with insulin-dependent diabetes mellitus. High concentrations of prorenin in combination with high values of glycated haemoglobin can be used as a predictor of development of microalbuminuria. [Diabetologia (1999
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