Effect of insulin on renal sodium and uric acid handling in essential hypertension

In normal subjects, insulin decreases the urinary excretion of sodium, potassium, and uric acid. We tested whether these renal effects of insulin are altered in insulin resistant hypertension. In 37 patients with essential hypertension, we measured the changes in urinary excretion of sodium, potassium, and uric acid in response to physiological euglycemic hyperinsulinemia (by using the insulin clamp technique at an insulin infusion rate of 6 pmol/min/kg). Glucose disposal rate averaged 26.6 ± 1.5 μmol/min/kg, ie, 20% lower than in normotensive controls (33.1 ± 2.1 μmol/min/kg, P = .015). In the basal state, fasting plasma uric acid concentrations were higher in men than women (P< .001), were positively related to body mass index (r = 0.38, P = .02), waist/hip ratio (r = 0.35, P< .05), and serum triglyceride levels (r = 0.59, P = .0001), and negatively related to HDL cholesterol concentrations (r = −0.59, P = .0001) and glucose disposal rate (r = 0.42, P< .01). Uric acid clearance, on the other hand, was inversely related to body mass index (r = 0.41, P = .01), plasma uric acid (r = 0.65, P< .0001) and triglyceride concentrations (r = 0.39, P< .02), and directly related to HDL cholesterol levels (r = 0.52, P< .001). During insulin infusion, blood pressure, plasma uric acid and sodium concentration, and creatinine clearance did not change. In contrast, hyperinsulinemia caused a significant decrease in the urinary excretion of uric acid (2.67 ± 0.12 to 1.86 ± .14 μmol/min/1.73 m2, P = .0001), sodium (184 ± 12 to 137 ± 14 μmol/min/1.73 m2, P = .0001), and potassium (81 ± 7 to 48 ± 4 μmol/min/1.73 m2, P = .0001). Both in absolute terms (clearance and fractional excretion rates) and percentagewise, these changes were similar to those found in normotensive subjects. Insulin-induced changes in urate excretion were coupled (r = 0.55, P< .0001) to the respective changes in sodium excretion. In hypertensive patients, higher uric acid levels and lower renal urate clearance rates cluster with insulin resistance and dyslipidemia. Despite insulin resistance of glucose metabolism, acute physiological hyperinsulinemia causes normal antinatriuresis, antikaliuresis, and antiuricosuria in these patients.