DECREASED URINARY KALLIKREIN WITH HYPERGLYCEMIA IN PATIENTS WITH SHORT-TERM INSULIN-DEPENDENT DIABETES-MELLITUS

The aim of the study was to evaluate the role of urinary kallikrein in the regulation of renal hemodynamics and sodium handling in insulin-d ependent diabetes mellitus (IDDM), and to test the effect of acutely i nduced hyperglycemia. Urinary kallikrein excretion was evaluated (1) u nder basal conditions and after stimulation with i.v. furosemide (0.5 mg . kg(-1)), (2) during glycemic clamp-induced eu- and hyperglycemia (5 and 12 mmol/L) and, (3) during time-controlled euglycemia in 21 sho rt-term IDDM patients without microalbuminuria and in 18 weight-, age- and gender-matched healthy controls. Sodium excretion and renal hemod ynamics using the clearances of inulin and para-amino-hippuric acid we re measured during examinations in both groups. The baseline urinary k allikrein excretion during clamp-induced euglycemia was comparable in diabetic and control subjects (10.89 +/- 5.98 versus 10.38 +/- 3.73 mU E . min(-1)), whereas it was decreased in the baseline for furosemide (5.77 +/- 3.22 versus 10.9 +/- 3.7 mUE . min(-1); y < 0.01) and even a fter furosemide administration (12.0 +/- 1.6 versus 21.3 +/- 2.0 mUE . min(-1) ; p < 0.01) while the patients were hyperglycemic. During int ravenous dextrose-induced hyperglycemia, the urinary kallikrein excret ion significantly declined in diabetic patients (10.89 +/- 5.98 versus 5.45 +/- 0.88 mUE . min(-1); y < 0.01), whereas it did not change in controls (10.38 +/- 3.73 versus 12.55 +/- 5.47 mUE . min(-1)). A decre ase in the fractional excretion of sodium and an attenuated rise in na triuresis after furosemide administration have been found in diabetic compared to control subjects. There were no significant relationships between kallikrein excretion and (1) renal hemodynamics, which was com parable in both groups, or (2) plasma renin activity, plasma and urine aldosterone and cortisol. We conclude that short-term IDDM without re nal hemodynamic alterations is associated with decreased basal and fur osemide-stimulated kallikrein excretion, which is directly related to the blood glucose level. The decreased activity of the renal kallikrei n-kinin system might be involved in the increased tendency to sodium r etention in diabetic patients. (C) 1998 Elsevier Science Inc.