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

Abstract

Background: Gadolinium contrast media (Gd-CM) are regarded as non-nephrotoxic or considerably less nephrotoxic than iodine contrast media (I-CM), and have therefore come to be used as a substitute for I-CM in patients with renal insufficiency in a variety of radiographic examinations.

Purpose: To investigate renal histomorphological changes caused by Gd-CM in comparison with I-CM after renal X-ray arteriography in an ischemic porcine model,and to evaluate these changes in relation to the nephrotoxicity of the CM used.

Material and methods: Test solutions: gadopentetate, gadodiamide, iohexol, gadobutrol,iopromide, iodixanol, mannitol, and saline. The experiments were performed on 152 animals. Each pig was randomized to receive one test solution injected into the balloon occluded(10 min) right renal artery. The kidneys were evaluated histomorphologically.The severity of histomorphological changes was graded subjectively: 15 minimal, 25 mild, 35 moderate, and 4=marked.

Results: The main histological changes were 1) proximal tubular and glomerular necrosis,2) hemorrhage/congestion of the cortex, medulla, and glomeruli, 3) proximal tubular vacuolation, and 4) protein-filled tubules in the cortex and medulla. Necrosis and hemorrhage/congestion were more frequent after injections with gadopentetate, mannitol solution iso-osmotic to gadopentetate, and gadobutrol compared to all other groups(P<0.001). The degree of necrosis and hemorrhage/congestion was related to the degree of impairment of renal function, but inversely related to vacuolation and tubular protein filling.

Conclusion: In ischemic porcine kidneys, the histomorphological changes caused by Gd-CM are similar to those caused by I-CM. Vacuolation appears to be independent of the osmolality and viscosity of the CM, and does not seem to be an indicator of renal impairment. "High-osmolal" Gd-CM are more nephrotoxic than "low- and iso-osmolal" I-CM when compared in equal volumes of concentrations, resulting in equal X-ray attenuation.