Conventional Amphotericin B Associated Nephrotoxicity in Patients With Hematologic Malignancies

Abstract

Introduction: Amphotericin B (AmB-d) is one of the most effective therapeutic options against frequently life-threatening systemic fungal infections in patients with hematologic malignancies. However, significant adverse effects including nephrotoxicity associated with its use limit its more widespread use. The objectives of our study were to determine the incidence of AmB-d associated nephrotoxicity, to evaluate clinical and epidemiological characteristics of patients, and to support the notion that conventional amphotericin B remains a valid therapeutic option among hematologic patients with proper patient selection.Materials and methods: A total of 110 patients with hematologic malignancies were admitted to our Hematology Unit between January 2014 and November 2017 who required anti-fungal therapy during intensive systemic chemotherapy. The incidence of AmB-d associated nephrotoxicity, side effect profile, time to nephrotoxicity, and clinical and epidemiological characteristics associated with treatment success were assessed retrospectively.Results: Of the 110 patients receiving AmB-d, 70 (63.6%) were male and 40 (36.4%) were female. The mean age of participants was 44 years. The most common diagnosis was acute myeloid leukemia (n=53, 48.2%), and the most common chemotherapy protocol was 7 + 3 remission-induction (cytarabine 100 mg/m² days 1-7, Idarubicin 12 mg/m² days 1-3; n=24, 21.8%). In 56.4% of the patients, antifungal therapy was given empirically. In 40 patients (36.4%), nephrotoxicity was observed following antifungal treatment, and only four patients had stage 3 renal failure. The mean duration of time to nephrotoxicity from initiation of amphotericin B was four days (min: 2, max: 31). All patients were found to receive at least one additional potential nephrotoxic treatment during the antifungal treatment process. Conclusion: AmB-d is associated with a significant risk of nephrotoxicity. In most hematological patients, antifungal treatment is initiated empirically, and patients received prolonged courses of treatment. Therefore, it is plausible to initiate such treatment with AmB-d, when one considers the already high treatment costs in this patient group as well as the fact that AmB-d offers similar efficacy to antifungal agents at a lower cost. AmB-d may be recommended as a first-line agent in this patient group with the introduction of newer and more costly antifungal agents when needed, on the basis of the fact that these patients can be closely monitored in a hospital setting, reversible nature of nephrotoxicity upon discontinuation, and rare occurrence of severe renal failure requiring dialysis.

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“…It is important to note that the liposomal formulation of AmB (AmBisome) which is composed of hydrogenated soy phosphatidylcholine, cholesterol, and distearoylphosphatidylglycerol along withother ingredients reduces the AmB toxicity but comes with high cost of treatment. As a result, novel approaches to reduceAmB-related nephrotoxicity are urgently needed ( Gursoy et al, 2021 ). Most plausible mechanism of nephrotoxicity is demonstrated in Figure 2 .…”

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“…The reported symptoms range from infusion-related reactions up to anaphylaxis, which can be prevented by drugs (e.g., corticoids, antihistamines, analgesics, etc.). Another serious side effect is a significant risk of nephrotoxicity which limits its use [10]. The formulation of AmB is an important topic of research with the aim to develop forms which improve its therapeutic effect and lead to less nephrotoxicity [11,12].…”