Calcineurin inhibitors and sirolimus

Burdmann, Emmanuel A.; Yu, Luis; Andoh, Takeshi F.; Perico, Norberto; Bennett, William M.

doi:10.1007/1-4020-2586-6_21

Cited by 4 publications

(8 citation statements)

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“…This infiltration is related to an increase of chemoattractant factors. 1 , 22 Different renal inflammatory processes, such as ischemia and reperfusion 22 , 28 and allograft rejection, 26 - 27 are characterized by an increase of chemoattractant factors including monocyte chemoattractant protein-1 27 - 28 , 30 and macrophage colony stimulating factor. 29 Monocytes cross the vascular endothelium and migrate to the damaged tissue, originating macrophages, which produce inflammatory mediators, among them, transforming growth factor (TGF-β), tumor necrosis factor (TNF-α), and interleukins 1, 6, and 12.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to the inflammatory mediators, macrophages are related to the enhancement of nitric oxide (NO), ROS, nitrotyrosine, and inflammation. 21 , 30 , 35 NO may be involved in macrophage action through oxidative stress in several manifestations of nephrotoxicity. During inflammation, NO is synthesized by iNOS (inducible NO synthase) that is induced by cytokine activation, and expressed in pathological conditions; macrophages are the principal source of NO production.…”

Section: Discussionmentioning

confidence: 99%

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Prior intake of Brazil nuts attenuates renal injury induced by ischemia and reperfusion

et al. 2018

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Prior intake of Brazil nuts attenuates renal injury induced by ischemia and reperfusion

et al. 2018

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“…This paper only discusses aspects of AKI related to calcineurin inhibitors. Acute nephrotoxicity is a hemodynamically mediated phenomenon characterized by the absence of permanent structural changes and reversibility with decrease or discontinuation of the offending or concomitant nephrotoxic (interacting) drug [123].…”

Section: Drug-induced Aki: Mechanisms and Clinical Significancementioning

confidence: 99%

“…Some mechanisms and mediators have been found. The renin–angiotensin–aldosterone system is involved [124], as are endothelin (a very potent constrictor of intrarenal vessels), nitric oxide, prostaglandins, free radicals, sympathetic system, vasopressin, atrial natriuretic factor(s), and some further substances [123]. The clinical presentation of acute CyA toxicity may present as AKI, asymptomatic increase of serum creatinine, hemolytic uremic syndrome (HUS), or a delayed recovery of renal graft function after renal transplantation.…”

Section: Drug-induced Aki: Mechanisms and Clinical Significancementioning

confidence: 99%

Nephrotoxicity as a cause of acute kidney injury in children

2008

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Many different drugs and agents may cause nephrotoxic acute kidney injury (AKI) in children. Predisposing factors such as age, pharmacogenetics, underlying disease, the dosage of the toxin, and concomitant medication determine and influence the severity of nephrotoxic insult. In childhood AKI, incidence, prevalence, and etiology are not well defined. Pediatric retrospective studies have reported incidences of AKI in pediatric intensive care units (PICU) of between 8% and 30%. It is widely recognized that neonates have higher rates of AKI, especially following cardiac surgery, severe asphyxia, or premature birth. The only two prospective studies in children found incidence rates of 4.5% and 2.5% of AKI in children admitted to PICU, respectively. Nephrotoxic drugs account for about 16% of all AKIs most commonly associated with AKI in older children and adolescents. Nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics, amphotericin B, antiviral agents, angiotensin-converting enzyme (ACE) inhibitors, calcineurin inhibitors, radiocontrast media, and cytostatics are the most important drugs to indicate AKI as significant risk factor in children. Direct pathophysiological mechanisms of nephrotoxicity include constriction of intrarenal vessels, acute tubular necrosis, acute interstitial nephritis, and-more infrequently-tubular obstruction. Furthermore, AKI may also be caused indirectly by rhabdomyolysis. Frequent therapeutic measures consist of avoiding dehydration and concomitant nephrotoxic medication, especially in children with preexisting impaired renal function.

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“…The pathogenesis of CsA nephrotoxicity has been investigated in animal and in vitro models and also in clinical studies. From these investigations it is clear that CsA nephropathy is a complex multifactorial process involving the vasculature, the glomerulus, the tubular epithelium, and the renal interstitium (3,4). There are certain histopathological similarities between CsA nephropathy and renal organ aging (26,34), giving rise to the possibility that common biochemical intermediates and pathways may exist.…”

mentioning

confidence: 99%

Cyclosporine A induces senescence in renal tubular epithelial cells

Jennings¹,

Koppelstaetter²,

Aydin³

et al. 2007

American Journal of Physiology-Renal Physiology

122

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The nephrotoxic potential of the widely used immunosuppressive agent cyclosporine A (CsA) is well recognized. However, the mechanism of renal tubular toxicity is not yet fully elucidated. Chronic CsA nephropathy and renal organ aging share some clinical features, such as renal fibrosis and tubular atrophy, raising the possibility that CsA may exert some of its deleterious effects via induction of a stress-induced senescent phenotype. We investigated this hypothesis in HK-2 cells and primary proximal tubular cells in vitro. CsA induced the production of H2O2, caused cell cycle arrest in the G0/G1 phase, and inhibited DNA synthesis. Furthermore, CsA exposure lead to a reduction of telomere length, increased p53 serine 15 phosphorylation, and caused an upregulation of the cell cycle inhibitor p21(Kip1) (CDKN1A) mRNA levels. CsA caused an increase in p16(INK4a) (CDKN2A) expression after a 13-day exposure in primary proximal tubular cells but not in HK-2 cells. Coincubation of cells with CsA and catalase was able to prevent telomere shortening and partially restored DNA synthesis. In summary, CsA induces cellular senescence in human renal tubular epithelial cells, which can be attenuated by scavenging reactive oxygen species.

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Calcineurin inhibitors and sirolimus

Cited by 4 publications

References 474 publications

Prior intake of Brazil nuts attenuates renal injury induced by ischemia and reperfusion

Prior intake of Brazil nuts attenuates renal injury induced by ischemia and reperfusion

Nephrotoxicity as a cause of acute kidney injury in children

Cyclosporine A induces senescence in renal tubular epithelial cells

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