Localization of the nephron site of gentamicin-induced hypercalciuria in the rat: A micropuncture study

1 In vivo renal micropuncture techniques were used to locate the nephron si te of hypercalciuria induced by acute gentamicin infusion in anaesthetized Sprague Dawley rats. Three series of experiments were conducted. The effect of gentamicin on calcium reabsorption in the proximal tubule (Series I) an d loop of Henle (Series II) was investigated using in vivo microperfusion w hereas the effect on distal calcium handling (Series III) was studied using in vivo microinfusion. 2 In all three experimental series, acute systemic gentamicin infusion at 0 .28 mg kg(-1) min(-1) caused significant hypercalciuria within 30 min of co mmencing drug infusion. Gentamicin had no effect on the rates of urine flow or sodium excretion. 3 Acute gentamicin infusion had no effect on unidirectional calcium reabsor ption in the proximal tubule or loop of Henle despite a simultaneous and hi ghly significant hypercalciuria at the whole kidney level. Net fluid reabso rption was also unaffected by the drug in these nephron segments. 4 Acute gentamicin infusion significantly increased the urinary recovery of calcium following microinfusion into early distal tubules, whereas urinary calcium recovery was decreased after microinfusion into late distal tubule s. 5 We conclude that acute gentamicin-induced hypercalciuria is mediated by a decrease in calcium reabsorption in the early distal tubule. Thus, the acu te hypercalciuric effect of gentamicin occurs at a different nephron site t o the nephrotoxic effects associated with longer-term administration of the drug. It is, therefore, unlikely that gentamicin-induced hypercalciuria is involved in the pathogenesis of subsequent proximal tubular cell injury.