THE INFLUENCE OF HYPERINSULINEMIA ON CALCIUM-PHOSPHATE METABOLISM IN RENAL-FAILURE

Background. Patients with renal failure are characterized by impaired insulin-mediated glucose uptake. Insulin plays a major role in the mai ntenance of phosphate homeostasis but it remains to be determined whet her in uraemia insulin-dependent renal and extrarenal phosphate dispos al is also affected. Methods. The effect of hyperinsulinaemia on serum concentrations of phosphate, ionized calcium and intact PTH as well a s renal excretion of calcium and phosphate was studied under euglycaem ic conditions (glucose clamp technique) in patients with advanced rena l failure and in healthy subjects. Fifteen patients with renal failure (mean serum creatinine 917 mu mol/l) and 12 control subjects were inc luded. All subjects underwent a 3-h euglycaemic clamp with constant in fusion of insulin (50 mU/m(2)/min) following a priming bolus. The urin e was collected for 3 h before and throughout the clamp. Results. The tissue insulin sensitivity (M/I) was lower in patients with renal fail ure than in control subjects (5.3+/-2.4 vs 6.7+/-1.8mg/kg/min per mU/m l, P = 0.001) but the phosphate lowering action of insulin was larger in patients with renal failure than in control subjects. Urinary calci um excretion increased (P < 0.05) and phosphate excretion did not chan ge during the clamp in both groups. Despite a decrease of serum ionize d calcium in the group of patients with renal failure and no change in the control group, plasma PTH fell significantly in both groups but t his effect was still significant after 180 min only in the renal failu re group. A significant correlation was observed between changes in se rum phosphate and PTH induced by hyperinsulinaemia (r=0.48, P<0.01)Con clusions. Phosphate-lowering effect of insulin is well preserved in se vere renal failure despite the resistance to insulin-stimulated glucos e uptake. The decrease of serum PTH observed during hyperinsulinaemia appears to be independent of serum ionized calcium.