Decreased Urinary Kallikrein with Hyperglycemia in Patients with Short-Term Insulin-Dependent Diabetes Mellitus

Abstract

The aim of the study was to evaluate the role of urinary kallikrein in the regulation of renal hemodynamics and sodium handling in insulin-dependent diabetes mellitus (IDDM), and to test the effect of acutely induced hyperglycemia. Urinary kallikrein excretion was evaluated (1) under 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 short-term IDDM patients without microalbuminuria and in 18 weight-, age- and gender-matched healthy controls. Sodium excretion and renal hemodynamics using the clearances of inulin and para-amino-hippuric acid were measured during examinations in both groups. The baseline urinary kallikrein excretion during clamp-induced euglycemia was comparable in diabetic and control subjects (10.89 ± 5.98 versus 10.38 ± 3.73 mUE · min −1), whereas it was decreased in the baseline for furosemide (5.77 ± 3.22 versus 10.9 ± 3.7 mUE · min −1; p < 0.01) and even after furosemide administration (12.0 ± 1.6 versus 21.3 ± 2.0 mUE · min −1; p < 0.01) while the patients were hyperglycemic. During intravenous dextrose-induced hyperglycemia, the urinary kallikrein excretion significantly declined in diabetic patients (10.89 ± 5.98 versus 5.45 ± 0.88 mUE · min −1; p < 0.01), whereas it did not change in controls (10.38 ± 3.73 versus 12.55 ± 5.47 mUE · min −1). A decrease in the fractional excretion of sodium and an attenuated rise in natriuresis 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 comparable in both groups, or (2) plasma renin activity, plasma and urine aldosterone and cortisol. We conclude that short-term IDDM without renal hemodynamic alterations is associated with decreased basal and furosemide-stimulated kallikrein excretion, which is directly related to the blood glucose level. The decreased activity of the renal kallikrein–kinin system might be involved in the increased tendency to sodium retention in diabetic patients.