Acute Renal Toxicity With Combined Use of Amphotericin B and Cyclosporine After Marrow Transplantation

Kennedy, Michael S.; Deeg, H. Joachim; Siegel, M B; Crowley, John; Storb, R; Ed, Thomas

doi:10.1097/00007890-198303000-00005

Cited by 152 publications

(39 citation statements)

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“…4,5 The etiology of alloBMT-associated renal failure is usually multifactorial. Risk factors for renal failure requiring dialysis after alloBMT include veno-occlusive disease (VOD), 2,3 age, 2 aminoglycosides, 3 the combined use of amphotericin B and cyclosporine, 6 amphotericin B alone, 7 elevated pre transplant serum creatinine, 3 radiation dose, 8,9 graft-versus-host disease (GVHD) 9 and cyclosporine. 10,11 Risk factors after autologous BMT include interstitial nephritis due to ciprofloxacin use.…”

Section: Discussionmentioning

confidence: 99%

Acute renal failure requiring dialysis after allogeneic blood and marrow transplantation identifies very poor prognosis patients

Hahn

Rondeau

Shaukat

et al. 2003

Bone Marrow Transplant

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Summary:We examined the incidence, risk factors and associated mortality of acute renal failure requiring dialysis (Renal Bearman Grade [BG] 3) in a 3-year cohort of 97 consecutive allogeneic blood and marrow transplantation (alloBMT) patients. In all, 20 (21%) developed Renal BG3 (all died by day +132) and 77 (79%) developed renal insufficiency (Renal BG1-2). Renal BG3 was a contributing or primary cause of death in 18 (90%) patients who continued to require dialysis at time of death. The two Renal BG3 patients whose deaths were not related to renal failure died on day +103 of hemorrhage and day +132 of underlying disease. By univariate analysis, age, unrelated donor, veno-occlusive disease (VOD) and grade III-IV acute graft-versus-host disease with hepatic involvement were significantly associated with Renal BG3. The multivariate model of time to Renal BG3 determined only a prior diagnosis of severe acute GVHD (RR ¼ 4.1, 95% CI 1.6-10.3, P ¼ 0.003) and VOD (RR ¼ 9.1, 95% CI 3.5-23.7, Po0.001) as significant independent predictors. Renal BG3 is generally considered a conditioning regimen-related toxicity. This study demonstrates that Renal BG3 is most commonly a complication of hepatic co-morbidities after allogeneic blood and marrow transplantation and identifies patients with a very poor prognosis.

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Section: Discussionmentioning

confidence: 99%

Acute renal failure requiring dialysis after allogeneic blood and marrow transplantation identifies very poor prognosis patients

Hahn

Rondeau

Shaukat

et al. 2003

Bone Marrow Transplant

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“…In other experiments (data not shown), when rabbits were treated for 28 days, greater levels of azotemia ensued to approach clinically significant renal insufficiency (>50% increase in serum creatinine). This lack of nephrotoxic potential is a clear advantage of itraconazole over amphotericin B, especially in the setting of organ transplantation, because of the potentially synergistic nephrotoxic interaction between CsA and amphotericin B (13). Itraconazole-induced elevated CsA levels have been reported to cause nephrotoxicity.…”

Section: Discussionmentioning

confidence: 99%

“…Unfortunately, successful treatment of this devastating infection is severely complicated in many patients by the development of dose-limiting nephrotoxicity. Treatment with amphotericin B is also hampered in transplant patients by potentially synergistic toxicity of this antifungal agent and cyclosporin A (CsA) (13).…”

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confidence: 99%

Itraconazole for experimental pulmonary aspergillosis: comparison with amphotericin B, interaction with cyclosporin A, and correlation between therapeutic response and itraconazole concentrations in plasma

Berenguer

Ali

Allende

et al. 1994

Antimicrob Agents Chemother

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Itraconazole and amphotericin B were compared by using a newly developed model of invasive pulmonary aspergillosis in rabbits immunosuppressed with methylprednisolone and cyclosporin A (CsA). Both itraconazole at 40 mg/kg (given orally) and amphotericin B at 1 mg/kg (given intravenously) had in vivo antifungal activity in comparison with controls. At these dosages, amphotericin B was more effective than itraconazole in reducing the tissue burden (loglo CFU per gram) of Aspergillus fumigatus (P < 0.05) and the number of pulmonary lesions (P < 0.01). However, there was considerable variation in the near-peak concentrations of itraconazole in plasma (median, 4.15 ,ug/ml; range, <0.5 to 16.8 ,g/ml) and a strong inverse correlation between concentrations of itraconazole in plasma and the tissue burden ofA.fumigatus. An inhibitory sigmoid maximum-effect model predicted a significant pharmacodynamic relationship (r = 0.87, P < 0.001) between itraconazole concentrations in plasma and antifungal activity as a function of the tissue burden ofA.fumigatus.This model demonstrated that levels in plasma of greater than 6 ,ug/ml were associated with a significantly greater antifungal effect. Levels in plasma of less than 6 ,g/ml were associated with a rapid decline in the antifungal effect. Itraconazole, in comparison with amphotericin B, caused a twofold elevation of CsA levels (P < 0.01) but was less nephrotoxic (P < 0.01). This study of experimental pulmonary aspergillosis demonstrated that amphotericin B at 1 mg/kg/day was more active but more nephrotoxic than itraconazole at 40 mg/kg/day, that itraconazole increased concentrations of CsA in plasma, and that the antifungal activity of itraconazole strongly correlated with concentrations in plasma in an inhibitory sigmoid maximum-effect model. These findings further indicate the importance of monitoring concentrations of itraconazole in plasma as a guide to increasing dosage, improving bioavailability, and optimizing antifungal efficacy in the treatment of invasive pulmonary aspergillosis.

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“…Cyclosporine is administered as prophylaxis and treatment for graft-versus-host disease which may occur following bone marrow transplantation, and is known to have nephrotoxic effects [8] , which have been reported to be potentiated by AmB [9] . While diuretic use has also been previously reported to potentiate the nephrotoxic effects of AmB [1] , it was not identifi ed in our study as a risk factor for AmB nephrotoxicity, possibly because the children received sodium when administered ticarcillin antimicrobial therapy.…”

Section: Discussionmentioning

confidence: 99%

Amphotericin B Dose Optimization in Children with Malignant Diseases

Nath

McLachlan²,

Shaw³

et al. 2007

Chemotherapy

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In this study, rational dosing guidelines for amphotericin B-deoxycholate (AmB) are proposed for children. AmB steady-state trough concentrations (C_ss,trough) and plasma creatinine concentrations (C_creat) were measured in 83 children (age: 10 months to 18 years) receiving prophylactic AmB therapy (1 mg/kg/day). Maximum tolerable AmB C_ss,trough were identified by determining the probability of large (>24%, 75th percentile) increases in C_creat after 6 days of AmB for a series of C_ss,trough ranges. Dose requirements were determined using a concentration-targeting approach. The 0.76–1.05 mg/l C_ss,trough range provided the maximum concentrations that still had a low probability (p < 0.29) of adverse renal effects. 1 mg/kg/day AmB produces C_ss,trough within this range for children weighing 25–45 kg. Lighter children (10–25 kg) require higher AmB doses (1.25–1.5 mg/kg/day) to achieve target C_ss,trough, while heavier children (45–55 kg) require lower doses (0.75 mg/kg/day). These starting dose guidelines may require individualization and prospective evaluation.

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Acute Renal Toxicity With Combined Use of Amphotericin B and Cyclosporine After Marrow Transplantation

Cited by 152 publications

References 0 publications

Acute renal failure requiring dialysis after allogeneic blood and marrow transplantation identifies very poor prognosis patients

Acute renal failure requiring dialysis after allogeneic blood and marrow transplantation identifies very poor prognosis patients

Itraconazole for experimental pulmonary aspergillosis: comparison with amphotericin B, interaction with cyclosporin A, and correlation between therapeutic response and itraconazole concentrations in plasma

Amphotericin B Dose Optimization in Children with Malignant Diseases

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