Role of ischemia in contrast-induced renal damage: an experimental study.

Abstract

Total and regional cortical blood flow was measured in dogs by the radioactive microsphere technique after renal damage of varying severity had been induced by combining selective injection of diatrizoate, iopamidol, or normal saline with a 10 min occlusion of the renal artery. There was extensive tubular and glomerular damage in the kidneys exposed to diatrizoate, but not in the kidneys exposed to saline. lopamidol caused intermediate changes. Average cortical blood flow was reduced from baseline levels in all groups 5 min after perfusion was restored. After 1 hr the flow had returned to the baseline level. Analysis of variance did not show a statistically significant difference among the groups. A tendency for redistribution of flow from outer to inner cortical layers was seen, but this was present in all groups. The flow changes detected in this study cannot explain the varying severity of renal damage. Circulation 69, No. 4, 783-789, 1984.INTRAVASCULAR ADMINISTRATION of radiographic contrast agents can lead to acute renal failure with oliguria or, rarely, anuria. More frequently, the renal impairment is clinically asymptomatic but detectable by biochemical tests for proteinurea and renal clearance. This occurs regularly in patients with preexisting renal disease, chronic diabetes, atherosclerosis, severe renal artery stenosis, or cardiac failure, and may be seen after renal transplantation, in association with myeloma or hyperuricemia. Dehydration or use of diuretics are often implicated.'-3The mechanisms underlying contrast-induced renal failure are largely unknown. Some of the factors that may be involved are ischemia, direct toxicity of the molecule of the contrast agent on tubular cells, alterations of the glomerular basement membrane by the molecule of the contrast agent, hyperosmolar solution or constituents of the solvent, or tubular obstruction from precipitation of insoluble material with resulting decreased filtration.Recently, we described a canine preparation that clearly discriminated between the nephrotoxicity induced by the currently used, high-osmolality agent diatrizoate and the recently introduced, low-osmolality agent iopamidol.4 The preparation is based on a standardized injection of the contrast agent combined with temporary occlusion of the renal artery for 10 min. The kidney is thus exposed to a high concentration of contrast agent for a prolonged time, and the small differences in nephrotoxicity between the media can be detected by radiologic and pathologic techniques. We postulated that this animal preparation could be used to investigate the relationship between renal perfusion and contrast-induced nephrotoxicity. With the radioactive microsphere technique, total as well as regional cortical blood flow can be estimated. The redistribution of cortical flow associated with decreased perfusion can also be detected.

Histomorphological changes after renal X-ray arteriography using iodine and gadolinium contrast media in an ischemic porcine model

“…This is supported by the fact that mannitol/io 1.96 with the same high osmolality as gadopentetate caused similar changes. Comparable macroscopically alterations were observed in canine kidneys injected with highly hyperosmotic solutions of sodium (18) or diatrizoate with an osmolality approximately 7 times that of plasma (29).…”

Gadolinium contrast media are more nephrotoxic than a low osmolar iodine medium employing doses with equal x-ray attenuation in renal arteriography: An experimental study in pigs1

“…In an initial pilot study, we did not notice any effect on renal function when the CM were injected into patent renal arteries as had been found in an earlier canine study from our laboratory (44). Therefore, an ischemic period was added to the experiment, a well-established procedure to potentiate the nephrotoxic effect of CM (35,40,45,46). It is well known from both clinical and experimental studies that prior preconditioning is often necessary to make living species susceptible to CM-induced renal failure.…”

Do contrast media (iomeprol, gadopentetate dimeglumine) deteriorate ischemia/reperfusion injury of the liver?

“…Intravenous contrast medium has been shown to be dangerous to ischemic renal tissue (4,5,9), and the risk of injury is dose dependent. Although the kidney concentrates the contrast medium and may thus be a particularly vulnerable target, contrast medium has been shown to cause direct injury to the pancreas in vitro and in vivo (17).…”