Acute Renal Failure Secondary to Imatinib Mesylate Treatment in Chronic Myeloid Leukemia

Pou, Mónica; Saval, N.; Vera, Manel; Saurina, Anna; Solé, Manel; Cervantes, Francisco; Botey, A

doi:10.1080/1042819031000079140

Cited by 66 publications

(43 citation statements)

References 7 publications

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“…20) The first one could occur when imatinib is used for patients with chronic myeloid leukemia, and was unlikely in our patients. Therefore, renal dysfunction observed in this study was most likely attributable to tubular damage, reported as acute tubular necrosis, 21) tubular vacuolization, 22) and partial Fanconi syndrome. 23) Renal dysfunction induced by imatinib sometimes becomes severe enough so as to require hemodialysis or irreversible even after discontinuation.…”

Section: Discussionmentioning

confidence: 96%

Imatinib Mesylate Has The Potential to Exert Its Efficacy by Down-Regulating The Plasma Concentration of Platelet-Derived Growth Factor in Patients With Pulmonary Arterial Hypertension

et al. 2010

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SummaryRecently, platelet-derived growth factor (PDGF) has been implicated in the abnormal proliferation and migration of pulmonary artery vascular smooth muscle cells. Imatinib meslylate, a PDGF receptor antagonist, has been reported to dramatically improve pulmonary arterial hypertension (PAH) in some human cases as well as animal models.Five patients with PAH (3 scleroderma-associated PAH and 2 idiopathic/familial PAH) taking no less than 2 PAH agents were treated with low-dose imatinib (100 mg/day) for 24 weeks. Imatinib was titrated up to 200 mg/day unless major complications were observed. Before and after the treatment, right heart catheterization, cardiopulmonary exercise test, respiratory function test, and plasma concentration measurements of PDGF-BB and vascular endothelial growth factor (VEGF) were performed. Plasma PDGF-BB levels were significantly decreased after 12 weeks of treatment (P = 0.04), while VEGF did not change. Although 24 week administration of imatinib did not show a significant effect on hemodynamics and exercise capacity, 2 patients with high plasma PDGF-BB levels showed a good initial response of more than a 15% decrease in pulmonary vascular resistance. Diffusion capacity of the lung for carbon monoxide significantly improved after 12 weeks of treatment (P < 0.01) and this improvement tended to be sustained for 24 weeks (P = 0.05). Renal dysfunction was observed in 3 patients during imatinib therapy.The upregulated PDGF-BB in patients with PAH could be suppressed by imatinib treatment, and also seemed to be one of the determinant factors for its efficacy. (Int Heart J 2010; 51: 272-276) Key words: Imatinib mesylate, Platelet-derived growth factor, Pulmonary arterial hypertension P ulmonary arterial hypertension (PAH) is a disease with a poor prognosis. Three major pathways have been identified as playing important roles in the pathophysiology of PAH; the endothelin pathway, nitric oxide pathway, and prostacyclin pathway. 1) These 3 pathways are associated with not only vasodilation, but also the unregulated proliferation of pulmonary artery vascular smooth muscle cells (PASMCs) in PAH patients. Several drugs which modulate each pathway are now available and have been shown to ameliorate PAH. Treatment with these drugs has been demonstrated to reverse intimal or medial thickening of the pulmonary artery in animal models.2-5) However, these effects are not so apparent in human PAH cases. In fact, the prognosis of PAH is improved to some extent with these drugs, but pulmonary vascular resistance (PVR) still remains over the normal range in almost all human PAH cases even after optimal treatment. Therefore, the development of drugs which regulate other pathways is still needed.Recently, platelet-derived growth factor (PDGF) has been implicated in the abnormal proliferation and migration of PASMCs and seems to play a pivotal role in the pathophysiology of PAH.6,7) Plasma PDGF-BB levels have been shown to be higher in PAH patients than in healthy controls.8) Imatinib mesylate is known t...

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Section: Discussionmentioning

confidence: 96%

Imatinib Mesylate Has The Potential to Exert Its Efficacy by Down-Regulating The Plasma Concentration of Platelet-Derived Growth Factor in Patients With Pulmonary Arterial Hypertension

et al. 2010

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“…Electronic microscopy showed vacuoles in some tubular cells, suggesting proximal tubular injury. Imatinib induced tubular necrosis has also been reported by Foringer and Pou [70], necessitating hemodialysis. In addition, one case of thrombotic microangiopathy (TMA) with renal and extra-renal expression has been reported, requiring definitive hemodyalisis [71].…”

Section: Other Targeted Therapies and Renal Toxicitymentioning

confidence: 86%

Renal toxicity of targeted therapies

2009

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The use of molecular targeted therapies for the treatment of cancer has increased over the last decade. The benefits of these compounds in terms of efficacy are often relatively modest and counter balanced by the occurrence of significant toxicities. Many of these newer agents used in clinical practice lack specificity and selectivity and have a propensity to inhibit multiple targets. The biological consequences of multi-kinase activity are poorly defined and numerous class-specific toxicities have been described. The kidney is an organ where most of these targeted pathways are expressed. Preclinical data and human renal biopsies have generated an understanding of the mechanisms involved in how targeted agents can cause renal toxicity. This review article discusses the observed nephrotoxicity with this burgeoning class of therapeutics and reviews both the biological reasons for its occurrence and possible ways to prevent significant renal damage.

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“…In three biopsy-proven cases, there was evidence of tubular damage in the form of acute tubular necrosis (ATN) [51], tubular vacuolization [52], and partial Fanconi syndrome with apical vacuoles in some tubular cells under electron microscopy examination [53]. Imatinib can inhibit PDGF-dependent renal mesangial cell proliferation by inhibitory effects on the PDGF receptor.…”

Section: Acute Kidney Injurymentioning

confidence: 97%

Renal Toxicities of Targeted Therapies

et al. 2015

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With the incorporation of targeted therapies in routine cancer therapy, it is imperative that the array of toxicities associated with these agents be well-recognized and managed, especially since these toxicities are distinct from those seen with conventional cytotoxic agents. This review will focus on these renal toxicities from commonly used targeted agents. This review discusses the mechanisms of these side effects and management strategies. Anti-vascular endothelial growth factor (VEGF) agents including the monoclonal antibody bevacizumab, aflibercept (VEGF trap), and anti-VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKIs) all cause hypertension, whereas some of them result in proteinuria. Monoclonal antibodies against the human epidermal growth factor receptor (HER) family of receptors, such as cetuximab and panitumumab, cause electrolyte imbalances including hypomagnesemia and hypokalemia due to the direct nephrotoxic effect of the drug on renal tubules. Cetuximab may also result in renal tubular acidosis. The TKIs, imatinib and dasatinib, can result in acute or chronic renal failure. Rituximab, an anti-CD20 monoclonal antibody, can cause acute renal failure following initiation of therapy because of the onset of acute tumor lysis syndrome. Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, can result in proteinuria. Discerning the renal adverse effects resulting from these agents is essential for safe treatment strategies, particularly in those with pre-existing renal disease.

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Acute Renal Failure Secondary to Imatinib Mesylate Treatment in Chronic Myeloid Leukemia

Cited by 66 publications

References 7 publications

Imatinib Mesylate Has The Potential to Exert Its Efficacy by Down-Regulating The Plasma Concentration of Platelet-Derived Growth Factor in Patients With Pulmonary Arterial Hypertension

Imatinib Mesylate Has The Potential to Exert Its Efficacy by Down-Regulating The Plasma Concentration of Platelet-Derived Growth Factor in Patients With Pulmonary Arterial Hypertension

Renal toxicity of targeted therapies

Renal Toxicities of Targeted Therapies

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