RENAL HEMODYNAMICS AND SODIUM HANDLING IN MODERATE RENAL-INSUFFICIENCY - THE ROLE OF INSULIN-RESISTANCE AND DYSLIPIDEMIA

Insulin infusion during euglycemia causes antinatiuresis and renal vas odilation in healthy humans, whereas the effects of acute insulin infu sion on tubular sodium handling and renal hemodynamics in chronic rena l disease are unknown. The response to euglycemic insulin infusion was investigated in two homogenous patient groups with a slight renal imp airment-one with nephrotic syndrome (GFR, 64 mL/min; N = 9) and one wi th non-nephrotic immunoglobulin A nephropathy (GFR, 70 mL/min; N = 8). In addition, nine renal transplant recipients (GFR, 44 +/- 6 mL/min) were investigated. The results were compared with those of 12 healthy controls (GFR, 105 +/- 4 mL/min). Renal hemodynamics and renal tubular sodium handling were estimated with inulin, p-aminohippurate, sodium, and lithium clearances. The results showed that patients with nephrot ic syndrome (5.0 +/- 0.4 mg/kg per minute) and renal transplant recipi ents (4.8 +/- 0.6 mg/kg per minute) had a significant lower metabolic clearance of glucose as compared with control subjects (7.9 +/- 0.4 mg /kg per minute), whereas patients with immunoglobulin A nephropathy (6 .7 +/- 0.6 mg/kg per minute) had a metabolic clearance of glucose that was similar to that of the controls. Despite insulin resistance to ca rbohydrate metabolism, insulin infusion still induced hypokalemia and antinatriuresis in patients with nephrotic syndrome and renal transpla nt recipients, Insulin infusion caused a significant 13% increase in R PF and lithium clearance in control subjects, and a positive Spearman rank correlation (R(s) = 0.41; P < 0.05) was observed between the chan ges in p-aminohippurate and lithium clearances during insulin infusion in the combined patient group, suggesting that impaired renal vasodil ation may contribute to abnormal proximal tubular sodium handling and sodium retention. The results also suggest that hypertriglyceridemia c ould be a factor contributing to abnormal proximal tubular sodium hand ling in chronic renal disease.