COMPARATIVE EFFECTS OF LOW-OSMOLAR AND HIGH-OSMOLAR CONTRAST-MEDIA ONTHE RENAL-FUNCTION DURING EARLY DEGENERATIVE GENTAMICIN-INDUCED NEPHROPATHY IN RATS

The nephrotoxic potentials of a high-osmolar contrast medium, diatrizo ate, and of a low-osmolar contrast medium, ioxaglate, were compared du ring early degenerative gentamicin-induced nephropathy in the rat. Mal e rats (13-22/group) were uninephrectomized. Six days later, the aorta was damped above the renal artery, and either diatrizoate or ioxaglat e was administered (1 ml/min for 3 min) via an aortic puncture into th e remaining kidney. Some of the rats received chronic treatment with g entamicin (50 mg/kg/day i.m., 4 days), starting 2 days before and endi ng 1 day after contrast medium administration. Two control groups, onl y one of which received gentamicin, were subjected to a 3-min renal is chemia. The creatinine clearance (CrCl) per 100 g body weight was dete rmined before and 24 and 48 h after contrast medium injection. A secon d study (6 rats/group) evaluated urinary N-acetyl-beta-D-glucosaminida se (NAG) excretion and the histologic appearance of the kidneys (blind ed analysis) in the same experimental groups. Gentamicin induced a sig nificant decrease in CrCl at baseline (0.35 +/- 0.19 vs. 0.41 +/- 0.19 ml/min; p < 0.01) and an increase in urinary NAG(128 +/- 92 vs. 39 +/ - 57 mu mol/h/mmol creatinine; p < 0.01). Taking into account these di fferences at baseline, univariate repeated-measures analysis showed th at on day 1 diatrizoate caused a more marked decrease in CrCl than iox aglate (p < 0.05), whether or not gentamicin was also administered. On day 2, the depressant effect of diatrizoate associated with gentamici n persisted (CrCl vs. day 0 = -0.19 +/- 0.10 ml/min), while that of di atrizoate alone returned to baseline (-0.05 +/- 0.24 ml/min). Converse ly, the effects of ioxaglate did not differ from those of the control groups at the two measuring times. Although the effects of contrast me dium-gentamicin interaction were not significant for urinary NAG, the gentamicin plus diatrizoate combination suggested greater toxic potent ial than the gentamicin plus ioxaglate combination on day 2 (NAG vs. d ay 0 = +260 +/- 528 vs. +22 +/- 119 mu mol/h/mmol creatinine). In cont rast to ioxaglate alone, which only induced vacuolization, diatrizoate alone provoked foci of tubular necrosis associated with vascular lesi ons. Gentamicin alone induced irregular vacuolization. Contrary to the findings for gentamicin plus diatrizoate, no necrotic foci were obser ved with gentamicin plus ioxaglate. The nephrotoxic potential of diatr izoate after intrarenal administration is greater than that of ioxagla te administered in the rat during the early degenerative phase of gent amicin-induced nephropathy.