Subacute effects of thiazide administration on renal hemodynamics and calcium metabolism

Summary

To elucidate the renal effects of thiazides as a function of sodium intake, 8 healthy volunteers without renal disease were studied at baseline and 1 day as well as 4 days after the administration of 100 mg hydrochlorothiazide/day. The subjects were compared on two different dietary sodium intakes (120 mmol/day and 220 mmol/day). Measurements comprised inulin clearance (Cin) and paraaminohippurate clearance (Cpah) by infusion clearance technique, total and ionised calcium, immunoreactive parathyroid hormone (1,84 iPTH), 1.25 (OH)₂ vitamin D₃, and indices of hemoconcentration. Acute administration of hydrochlorothiazide (HCTZ) caused no change in Cin (before 111 ± 3 ml/min 1.73 m² ; 24 h after, 107 ± 2 ml/min 1.73 m²) or Cpah (before, 579 ± 9 ml/min 1.73 M²; after, 584 ± 12 ml/min 1.73 m²), while a significant (P < 0.01) decrease was noted on the 4th day after 100 mg HCTZ/day and normal sodium intake. No significant change of creatinine clearance (Ccr) was seen with either manouever. Renal hemodynamic changes after HCTZ administration were marginal when hemoconcentration was prevented by a high salt intake. Acute administration (1 h) of HCTZ caused suppression of 1,84 iPTH (before, 2.3 ±0.5 pmol/l; after, 1.9 ± 0.2 pmol/l; P < 0.01), but after 4 days a lower ionised calcium (baseline, 1.25 ± 0.01 mmol/l; day 5, 1.20 ± 0.02 mmol/l; P < 0.01) was noticed in parallel with hemoconcentration, metabolic alkalosis, and reduced 1,25 (OH)₂ vitamin D₃ concentrations. The level of 1,84 iPTH was elevated. We conclude that (i) hydrochlorothiazide does not affect the renal hemodynamics if hemoconcentration is avoided and (ii) hydrochlorothiazide acutely lowers PTH, while subacutely metabolic alkalosis and decreased ionised calcium may occur with concomitant increase in 1,84 iPTH and decrease in 1,25 (OH)₂ vitamin D₃ concentrations unless hemoconcentration is prevented.