Abstract:The DNA fragmentation of MDCK cells induced by diatrizoate is related to its hypertonicity in this in vitro model of radiocontrast cytotoxicity. Nuclear disintegration with subsequent cell death may contribute to the pathophysiology of radiocontrast-induced nephropathy, particularly in the hypertonic/hypoxic environment of the renal medulla. The present results underscore the importance of avoiding hyperosmolal urine states in patients at high risk of radiocontrast-induced nephropathy.
“…[11][12][13][14] The direct toxic effects of CM have been studied in various cells, including renal epithelial and mesangial cells. 15 The functional and structural changes observed as a result of CM action included cell death, a decrease in cell viability, and an increase in brush border and lysosomal enzyme activity; 16 cellular DNA fragmentation; 17 downregulation of signaling molecules involved in cell survival such as Akt and upregulation of signaling molecules in cell death such as the p38 and c-Jun N-terminal kinase members of the mitogenactivated protein kinases and the transcription factor nuclear factor kB as well as caspase activation. 13,18,19 Nuclear factor kB and c-Jun N-terminal kinases are believed to be involved in the upregulation of the proinflammatory cytokine interleukin-8 (IL-8).…”
Section: Pathophysiology Of Ci-akimentioning
confidence: 99%
“…Cell cycle arrest may result as a consequence of cellular damage, in particular DNA damage, thus preventing the cell from entering cell division. Cellular DNA damage by CM has been reported; 17 and therefore, it is feasible that the CM may upregulate these cell cycle arrest markers in renal tubule cells and may be detected in urine after CM-induced renal injury.…”
Contrast-induced acute kidney injury (CI-AKI) is a problem associated with the use of iodinated contrast media, causing kidney dysfunction in patients with preexisting renal failure. It accounts for 12% of all hospital-acquired kidney failure and increases the length of hospitalization, a situation that is worsening with increasing numbers of patients with comorbidities, including those requiring cardiovascular interventional procedures. So far, its diagnosis has relied upon the rise in creatinine levels, which is a late marker of kidney damage and is believed to be inadequate. Therefore, there is an urgent need for biomarkers that can detect CI-AKI sooner and more reliably. In recent years, many new biomarkers have been characterized for AKI, and these are discussed particularly with their use in known CI-AKI models and studies and include neutrophil gelatinase-associated lipocalin, cystatin C (Cys-C), kidney injury molecule-1, interleukin-18, N-acetyl-β-d-glucosaminidase, and L-type fatty acid-binding protein (L-FABP). The potential of miRNA and metabolomic technology is also mentioned. Early detection of CI-AKI may lead to early intervention and therefore improve patient outcome, and in future any one or a combination of several of these markers together with development in technology for their analysis may prove effective in this respect.
“…[11][12][13][14] The direct toxic effects of CM have been studied in various cells, including renal epithelial and mesangial cells. 15 The functional and structural changes observed as a result of CM action included cell death, a decrease in cell viability, and an increase in brush border and lysosomal enzyme activity; 16 cellular DNA fragmentation; 17 downregulation of signaling molecules involved in cell survival such as Akt and upregulation of signaling molecules in cell death such as the p38 and c-Jun N-terminal kinase members of the mitogenactivated protein kinases and the transcription factor nuclear factor kB as well as caspase activation. 13,18,19 Nuclear factor kB and c-Jun N-terminal kinases are believed to be involved in the upregulation of the proinflammatory cytokine interleukin-8 (IL-8).…”
Section: Pathophysiology Of Ci-akimentioning
confidence: 99%
“…Cell cycle arrest may result as a consequence of cellular damage, in particular DNA damage, thus preventing the cell from entering cell division. Cellular DNA damage by CM has been reported; 17 and therefore, it is feasible that the CM may upregulate these cell cycle arrest markers in renal tubule cells and may be detected in urine after CM-induced renal injury.…”
Contrast-induced acute kidney injury (CI-AKI) is a problem associated with the use of iodinated contrast media, causing kidney dysfunction in patients with preexisting renal failure. It accounts for 12% of all hospital-acquired kidney failure and increases the length of hospitalization, a situation that is worsening with increasing numbers of patients with comorbidities, including those requiring cardiovascular interventional procedures. So far, its diagnosis has relied upon the rise in creatinine levels, which is a late marker of kidney damage and is believed to be inadequate. Therefore, there is an urgent need for biomarkers that can detect CI-AKI sooner and more reliably. In recent years, many new biomarkers have been characterized for AKI, and these are discussed particularly with their use in known CI-AKI models and studies and include neutrophil gelatinase-associated lipocalin, cystatin C (Cys-C), kidney injury molecule-1, interleukin-18, N-acetyl-β-d-glucosaminidase, and L-type fatty acid-binding protein (L-FABP). The potential of miRNA and metabolomic technology is also mentioned. Early detection of CI-AKI may lead to early intervention and therefore improve patient outcome, and in future any one or a combination of several of these markers together with development in technology for their analysis may prove effective in this respect.
“…In addition, in an in vitro model with a renal epithelial cell line, DNA fragmentation (a marker of apoptosis) was increased in cells exposed to hyperosmolar contrast media, and the degree of fragmentation was proportional to the osmolality of the contrast medium. 36 Thus, there is evidence of a direct cytotoxic effect of contrast media that is independent of hypoxia and may be related to hyperosmolality of the contrast agent. However, when the renal effects of isoosmolar contrast media, which have the lowest osmolality, were compared with the effects of hypo-and hyperosmolar contrast agents, there was no reduction in renal abnormalities with the iso-osmolar agents.…”
WITH THE INCREASING USE OF CONTRAST MEDIA in diagnostic and interventional procedures, nephropathy induced by contrast media has become the third leading cause of hospital-acquired acute renal failure. It is also associated with a significant risk of morbidity and death. The current understanding of the pathogenesis indicates that contrast-medium nephropathy is caused by a combination of renal ischemia and direct toxic effects on renal tubular cells. Patients with pre-existing renal insufficiency, diabetes mellitus and congestive heart failure are at highest risk. Risk factors also include the type and amount of contrast medium administered. Therapeutic prevention strategies are being extensively investigated, but there is still no definitive answer. In this article, we review the current evidence on the causes, pathogenesis and clinical course of contrast-medium nephropathy as well as therapeutic approaches to its prevention evaluated in clinical trials.
“…Radiocontrast results in apoptosis of tubular epithelial cells in vivo (54) and in cultured cells (47,55). Hizoh et al (47) found that contrast-induced apoptosis in cultured cells was due to hyperosmolarity and not hypoxia. In contrast, other studies have found that epithelial cell apoptosis occurs after contrast-induced decreases in medullary oxygenation (54).…”
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