ACUTE GENTAMICIN-INDUCED HYPERCALCIURIA AND HYPERMAGNESIURIA IN THE RAT - DOSE-RESPONSE RELATIONSHIP AND ROLE OF RENAL TUBULAR INJURY

1 Standard renal clearance techniques were used to assess the dose-res ponse relationship between acute gentamicin infusion and the magnitude of hypercalciuria and hypermagnesiuria in the anaesthetized Sprague-D awley rat. Also investigated were whether these effects occurred indep endently of renal tubular cell injury. 2 Acute gentamicin infusion was associated with a significant hypercalciuria and hypermagnesiuria evi dent within 30 min of drug infusion. The magnitude of these responses was related to the dose of drug infused (0.14-1.12 mg kg(-1) min(-1)). Increased urinary electrolyte losses resulted from a decreased tubula r reabsorption of calcium and magnesium. 3 A rapid dose-related increa se in urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion was also observed in response to gentamicin infusion. However, there was no ev idence of renal tubular cell injury and no myeloid bodies were observe d within the lysosomes of the proximal tubular cells. Gentamicin may t hus interfere with the mechanisms for cellular uptake and intracellula r processing of NAG causing increased NAG release into the tubular lum en. 4 The absence of changes in renal cellular morphology indicates th at the excessive renal losses of calcium and magnesium were an effect of gentamicin per se and not the result of underlying renal tubular in jury. The renal effects described in this paper were apparent after ad ministration of relatively low total drug doses, and with plasma conce ntrations calculated to be within the clinical range. These findings s uggest that disturbances of plasma electrolyte homeostasis could occur in the absence of overt renal injury in patients receiving aminoglyco side antibiotics.