Ifosfamide‐induced nephrotoxicity in 593 sarcoma patients: A report from the Late Effects Surveillance System

Stöhr, Wolfgang; Paulides, Marios; Bielack, Stefan; Jürgens, H.; Treuner, J.; Rossi, Rainer; Langer, Thor﻿s﻿ten; Beck, J. D.

doi:10.1002/pbc.20858

Cited by 99 publications

(65 citation statements)

References 40 publications

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“…There are various renal side effects associated with ifosfamide. Toxicity involves mainly the proximal-and in rare cases, the distal-renal tubules [106]. It leads to ifosfamide-induced proximal tubulopathy, which results in a loss of phosphate and HCO 3 − (proximal RTA) [107].…”

Section: Ifosfamidementioning

confidence: 99%

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Drug-induced acid-base disorders

et al. 2014

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The incidence of acid-base disorders (ABDs) is high, especially in hospitalized patients. ABDs are often indicators for severe systemic disorders. In everyday clinical practice, analysis of ABDs must be performed in a standardized manner. Highly sensitive diagnostic tools to distinguish the various ABDs include the anion gap and the serum osmolar gap. Drug-induced ABDs can be classified into five different categories in terms of their pathophysiology: (1) metabolic acidosis caused by acid overload, which may occur through accumulation of acids by endogenous (e.g., lactic acidosis by biguanides, propofol-related syndrome) or exogenous (e.g., glycol-dependant drugs, such as diazepam or salicylates) mechanisms or by decreased renal acid excretion (e.g., distal renal tubular acidosis by amphotericin B, nonsteroidal antiinflammatory drugs, vitamin D); (2) base loss: proximal renal tubular acidosis by drugs (e.g., ifosfamide, aminoglycosides, carbonic anhydrase inhibitors, antiretrovirals, oxaliplatin or cisplatin) in the context of Fanconi syndrome; (3) alkalosis resulting from acid and/or chloride loss by renal (e.g., diuretics, penicillins, aminoglycosides) or extrarenal (e.g., laxative drugs) mechanisms; (4) exogenous bicarbonate loads: milk-alkali syndrome, overshoot alkalosis after bicarbonate therapy or citrate administration; and (5) respiratory acidosis or alkalosis resulting from drug-induced depression of the respiratory center or neuromuscular impairment (e.g

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Section: Ifosfamidementioning

confidence: 99%

“…Proximal RTA in the context of RFS is not rare in patients treated with ifosfamide (4.6 % of patients). Risk factors include cumulative dose of ifosfamide and younger age [106]. The frequency of subclinical tubular dysfunction is up to 90 % [114,115].…”

Section: Ifosfamidementioning

confidence: 99%

Drug-induced acid-base disorders

et al. 2014

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“…Chemotherapeutic agents with well documented early nephrotoxicity are ifosfamide, cisplatin, and carboplatin (5)(6)(7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Renal Dysfunction and Elevated Blood Pressure in Long-Term Childhood Cancer Survivors

Knijnenburg¹,

Jaspers²,

Pal³

et al. 2012

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Little is known about renal function and blood pressure (BP) in long-term childhood cancer survivors. This cross-sectional study evaluated prevalence of these outcomes and associated risk factors in long-term childhood cancer survivors at their first visit to a specialized outpatient clinic.Design, Setting, Participants, & Measurements Estimated GFR; percentages of patients with albuminuria, hypomagnesemia, and hypophosphatemia; and BP were assessed in 1442 survivors $5 years after diagnosis. Multivariable logistic regression analyses were used to estimate effect of chemotherapy, nephrectomy, and radiation therapy on the different outcomes.Results At a median age of 19.3 years (interquartile range, 15.6-24.5 years), 28.1% of all survivors had at least one renal adverse effect or elevated BP. The median time since cancer diagnosis was 12.1 years (interquartile range, 7.8-17.5 years). High BP and albuminuria were most prevalent, at 14.8% and 14.5%, respectively. Sixty-two survivors (4.5%) had an estimated GFR ,90 ml/min per 1.73 m 2 . Survivors who had undergone nephrectomy had the highest risk for diminished renal function (odds ratio, 8.6; 95% confidence interval [CI], 3.4-21.4). Combined radiation therapy and nephrectomy increased the odds of having elevated BP (odds ratio, 4.92; 95% CI, 2.63-9.19), as did male sex, higher body mass index, and longer time since cancer treatment.Conclusion Almost 30% of survivors had renal adverse effects or high BP. Therefore, monitoring of renal function in high-risk groups and BP in all survivors may help clinicians detect health problems at an early stage and initiate timely therapy to prevent additional damage.

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“…Ifosfamide (IFO) is an alkylating oxazaphosphorine antitumor prodrug (1,2), the clinical effectiveness of which is severely limited by a high incidence of nephrotoxicity (3)(4)(5), especially in children (6,7). Neither the biochemical mechanism(s) by which IFO damages the kidney nor the means by which other agents may reverse this damage is clearly understood.…”

Section: Introductionmentioning

confidence: 99%

“…Neither the biochemical mechanism(s) by which IFO damages the kidney nor the means by which other agents may reverse this damage is clearly understood. Both in patients and in an animal model, IFO induces a persistent Fanconi syndrome and significant proximal renal tubular dysfunction associated with a reduced glomerular filtration rate, glucosuria, aminoaciduria, phosphaturia, and bicarbonaturia (3)(4)(5)(6)(7)(8). Nephrotoxicity is a common and potentially serious complication of treatment despite coadministration of the uroprotective agent, 2-mercaptoethane sulfonic acid (MESNA; refs.…”

Section: Introductionmentioning

confidence: 99%

Ifosfamide-Induced Nephrotoxicity: Mechanism and Prevention

et al. 2006

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The efficacy of ifosfamide (IFO), an antineoplastic drug, is severely limited by a high incidence of nephrotoxicity of unknown etiology. We hypothesized that inhibition of complex I (C-I) by chloroacetaldehyde (CAA), a metabolite of IFO, is the chief cause of nephrotoxicity, and that agmatine (AGM), which we found to augment mitochondrial oxidative phosphorylation and B-oxidation, would prevent nephrotoxicity. Our model system was isolated mitochondria obtained from the kidney cortex of rats treated with IFO or IFO + AGM.

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Ifosfamide‐induced nephrotoxicity in 593 sarcoma patients: A report from the Late Effects Surveillance System

Abstract: Ifosfamide-induced nephrotoxicity was found in 4.6% of patients. Risk factors were the cumulative ifosfamide dose and young age at treatment.

Cited by 99 publications

References 40 publications

Drug-induced acid-base disorders

Drug-induced acid-base disorders

Renal Dysfunction and Elevated Blood Pressure in Long-Term Childhood Cancer Survivors

Ifosfamide-Induced Nephrotoxicity: Mechanism and Prevention

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