ATRIAL-NATRIURETIC-PEPTIDE INCREASES URINARY ALBUMIN EXCRETION IN MENWITH TYPE-1 DIABETES-MELLITUS AND ESTABLISHED MICROALBUMINURIA

Raised plasma concentrations of atrial natriuretic peptide (ANP) have been reported in patients with Type 1 (insulin dependent) diabetes mel litus (DM) who have poor glycaemic control and are associated with the presence of microalbuminuria. To test the hypothesis that elevations in plasma ANP concentration increase urinary albumin excretion in Type 1 DM, we have studied the effects of intravenous infusions of ANP in eight such subjects with established microalbuminuria. Blood glucose w as maintained between 4 and 7 mmol l(-1) in all subjects for the durat ion of studies; after euglycaemia had been established, a standard ora l water load (20 ml kg(-1) plus replacement of urinary losses) was giv en. Once steady state diuresis was attained, subjects received intrave nous infusion of either placebo (0.9 % saline), low dose (2.5 pmol kg( -1) min(-1)) or high dose (5.0 pmol kg(-1) kg min(-1)) ANP solution in a randomized, double-blind protocol. Infusion of ANP caused a dose-de pendent increase in urinary albumin excretion rate (placebo, 11.3 (SD 8.9) to 8.7 (SD 6.8) mu g min(-1); low dose ANP, 12.4 (SD 9.9) to 26.5 (SD 27.5) mu g min(-1), p < 0.01; high dose ANP 10.3 (SD 7.3) to 36.6 (SD 28.5) mu g min(-1), p < 0.001, ANOVA). Only high dose ANP caused an increase in urine flow. Blood glucose remained unchanged in all stu dies. We conclude that intravenous infusions of ANP cause a dose-depen dent increase in urinary albumin excretion rate in Type 1 DM subjects with microalbuminuria. These data support the hypothesis that ANP has albuminuric actions which may contribute to microalbuminuria in Type 1 DM. (C) 1998 John Wiley & Sons, Ltd.