Renal hemodynamics and sodium handling in moderate renal insufficiency: the role of insulin resistance and dyslipidemia.

Insulin infusion during euglycemia causes antinatriuresis and renal vasodilation in healthy humans, whereas the effects of acute insulin infusion on tubular sodium handling and renal hemodynamics in chronic renal disease are unknown. The response to euglycemic insulin infusion was investigated in two homogeneous patient groups with a slight renal impairment-one with nephrotic syndrome (GFR, 64 mL/min; N = 9) and one with 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 nephrotic syndrome (5.0 +/- 0.4 mg/kg per minute) and renal transplant recipients (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 carbohydrate metabolism, insulin infusion still induced hypokalemia and antinatriuresis in patients with nephrotic syndrome and renal transplant recipients. Insulin infusion caused a significant 13% increase in RPF and lithium clearance in control subjects, and a positive Spearman rank correlation (Rs = 0.41; P < 0.05) was observed between the changes in p-aminohippurate and lithium clearances during insulin infusion in the combined patient group, suggesting that impaired renal vasodilation may contribute to abnormal proximal tubular sodium handling and sodium retention. The results also suggest that hypertriglyceridemia could be a factor contributing to abnormal proximal tubular sodium handling in chronic renal disease.