Induction, prevention and mechanisms of contrast media-induced acute renal failure

This study describes the development of an experimental model of reversible acute renal failure following infusion of contrast media radiographic dye. Experiments were also performed to investigate possible methods of prevention as well as examine single nephron mechanisms involved in the pathogenesis of the renal failure. Acute renal failure was consistently produced by indomethacin treatment (18 mg/kg) and an intravenous infusion of contrast media (7 ml/kg) into New Zealand rabbits that had been on a low sodium diet for one week. Glomerular filtration rate (GFR), measured by daily creatinine clearance in unanesthetized animals, was significantly decreased (P < 0.001) 24, 48, and 72 hours following infusion of the contrast dye. Two weeks after induction of acute renal failure, GFR had returned to control. GFR was unchanged during the same time period when the sodium deprived rabbits were given either indomethacin or contrast media alone. Chronic administration of DOCA (1 mg/kg s.c.) and saline drinking water which increased sodium and solute excretions and decreased plasma renin activity also prevented the decrease in GFR. However, acute infusion of either saline or mannitol, which transiently increased sodium and solute excretions and decreased plasma renin activity, did not protect against the development of acute renal failure. Light microscopy revealed no glomerular or tubular changes and no visible obstruction. Micropuncture experiments were performed on three additional groups of anesthetized rabbits: control, acute renal failure, and recovery. Recovery rabbits were allowed a two week period after renal failure before they were micropunctured. Single nephron filtration rate decreased from 19.55 ± 1.9 to 9.54 ± 1.9 nl/min during renal failure but returned to 17.73 ± 2.4 nl/min two weeks later. Proximal tubular hydrostatic pressure (PT) and glomerular capillary pressure (PGC), estimated by stop-flow pressure, were unchanged following induction of acute renal failure. The net hydrostatic pressure favoring filtration, (PGC-PT), was significantly greater than the oncotic pressure in the efferent arteriole, (II(E)), in all three groups. Since the rabbit glomerular capillary was in filtration pressure disequilibrium a unique value for the glomerular ultrafiltration coefficient (Kf) was calculated. Kf was significantly decreased from 1.28 ± 0.15 to 0.49 ± 0.10 during renal failure, but returned to 1.62 ± 0.39 nl/min/mm Hg after recovery. Renal blood flow, measured with an electromagnetic flow probe, was not different and averaged 22 ± 2, 24 ± 2, and 32 ± 7 ml/min in the control, acute renal failure, and recovery groups, respectively. The results of this study show that low sodium intake followed by indomethacin and contrast media lead to reversible acute renal failure in the rabbit. The renal insufficiency can be prevented by high sodium intake and DOCA treatment but is not altered by acute saline or mannitol infusions. The results of these studies also indicate that the rabbit glomerular capillary is in filtration pressure disequilibrium; and the decrease in GFR associated with contrast media-induced acute renal failure is a result of a significant decrease in single nephron filtration rate precipitated by a significant, but reversible decrease in the glomerular ultrafiltration coefficient.