Direct toxic effect of the radiocontrast agent diatrizoate on renal proximal tubule cells

Abstract

The pathophysiology of radiocontrast agent-induced acute renal failure is presently unclear. To test for a possible direct deleterious effect of diatrizoate, a commonly used radiocontrast agent, on renal tubule cells, suspensions enriched in rabbit proximal tubule segments were incubated with sodium diatrizoate. After these manipulations, a variety of well-established metabolic parameters to quantitate the extent of cell injury were measured. Diatrizoate sodium (25 mM) produced significant declines in tubule K+, ATP, and total adenine nucleotide (TAN) contents, significant decreases in tubule basal and uncoupled respiratory rates, and a significant increase in tubule Ca2+ content, demonstrating the development of cell injury induced by diatrizoate. These effects were dose related and were progressive with increasing incubation time from 97.5 to 157.5 min. The effects of N-methylglucosamine (meglumine) on renal tubule cell viability was also evaluated. Meglumine is a low molecular weight amino-substituted cationic compound and is commonly added to radiocontrast dye solutions. Meglumine (25 mM) had significant effects to lower tubule K+ content and to decrease both tubule basal and uncoupled respiratory rates. These alterations were slightly additive to diatrizoate in that meglumine diatrizoate produced greater alterations in tubule-metabolic parameters compared to diatrizoate sodium. A period of 22.5 min of hypoxia also caused deleterious changes in each of these quantitative indices of cell viability, and diatrizoate potentiated the degree of hypoxia-induced cell injury. These results demonstrate that the radiocontrast agent, diatrizoate, is directly toxic to renal proximal tubule cells. Meglumine, a cation added to diatrizoate containing radiocontrast solutions, also had a moderate toxic effect on renal epithelial cells and added to the toxicity of diatrizoate. Diatrizoate also aggravated the degree of cell injury induced by a 22.5-min period of hypoxia. These experiments thus provide evidence for a direct toxic effect of diatrizoate on proximal renal tubule cells which was additive to hypoxic cell injury.

Serum Neutrophil Gelatinase-Associated Lipocalin Levels In Early Detection Of Contrast-Induced Nephropathy

“…Filiopoulos et al reported that NGAL level at the 6 th hour had a sensitivity and specificity of 100% [16]. Plasma NGAL has been reported to be a highly specific and objective marker for the diagnosis of ARF [17][18][19]. In the current study, NGAL had an AUC level of 0.98, a sensitivity of 100% and a specificity of 95%.…”

Risk of contrast-induced nephropathy in hospitalized patients with cirrhosis

“…In vitr o and animal studies sug g est that damag e secondary to iodinated contrast to the kidneys is likely mediated by a combination of toxic or obstructive injury to the renal tubules, ischemic injury by reactive oxygen species, and renal medullary hypoxia. The predominant factor is likely to be renal medullary hypoxia, in which adenosine, calcium, and endothelin bring about intrarenal vasoconstriction after contrast exposure [17,[20][21][22][23][24][25] . Tubular toxicity is also thought to play a role in CIN through both direct nephrotoxicity and tubular obstruction.…”

Contrast medium induced nephropathy in patients undergoing percutaneous coronary intervention for acute coronary syndrome: differences in STEMI and NSTEMI

“…In patients with ACS undergoing an emergent coronary intervention there are two well-known reasons for developing acute renal impairment. The first one is the direct toxicity of contrast medium [13] and the second one is the frequent systemic hemodynamic alteration, like blood pressure irregularities and a reduced systemic perfusion pressure in acute cardiac events [35]. The direct toxicity seems to be worse in patients with pre-existing renal insufficiency, diabetes mellitus, and atherosclerosis.…”