Increase in serum prorenin precedes onset of microalbuminuria in patients with insulin-dependent diabetes mellitus

Aims/hypothesis. The renin-angiotensin system is possibly involved in the p athogenesis of diabetic nephropathy. The most striking change in renin-angi otensin system components in blood of patients with diabetic nephropathy is an increased prorenin concentration. We investigated prospectively serum c oncentrations of renin-angiotensin system components and the time course of prorenin increase in normoalbuminuric diabetic patients developing microal buminuria. Methods. Patients (n = 199) with Type I (insulin-dependent) diabetes mellit us and normoalbuminuria at baseline were prospectively followed for 10 year s. The prorenin concentrations and other variables possibly associated with the occurrence of microalbuminuria, were investigated by Cox-regression an alysis. Results. Of the patients 29 developed microalbuminuria. Glycated haemoglobi n values were higher at baseline in these patients. Serum prorenin was simi lar at baseline but rose in the 29 patients before the development of micro albuminuria and was stable in patients with stable albumin excretion. Renin , angiotensinogen and angiotensin converting enzyme serum concentrations we re stable in both groups. Prorenin and glycated haemoglobin were independen t progonostic 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 m icroalbuminuria in normotensive patients with insulin-dependent diabetes me llitus. High concentrations of prorenin in combination with high values of glycated haemoglobin can be used as a predictor of development of microalbu minuria.