Does Lipid Emulsion Reduce Amphotericin B Nephrotoxicity? A Systematic Review and Meta-analysis

Mistro, Sóstenes; Maciel, Isis de M.; Menezes, Rouseli G. de; Maia, Zuinara Pereira Gusmão; Schooley, Robert T.; Badaró, Roberto

doi:10.1093/cid/cis290

Cited by 77 publications

(56 citation statements)

References 9 publications

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“…Liposomal AmB has an improved renal safety profile compared to conventional AmB. 61 Two pathogenic mechanisms have been suggested to explain AKI with AmB use. 62 The antifungal effect of AmB is related to its ability to alter membrane permeability of fungal cells, which leads to cell death.…”

Section: Antifungal Agents Amphotericin Bmentioning

confidence: 99%

Drug-induced impairment of renal function

Pazhayattil¹,

Shirali²

2014

IJNRD

118

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Pharmaceutical agents provide diagnostic and therapeutic utility that are central to patient care. However, all agents also carry adverse drug effect profiles. While most of these are clinically insignificant, some drugs may cause unacceptable toxicity that impacts negatively on patient morbidity and mortality. Recognizing adverse effects is important for administering appropriate drug doses, instituting preventive strategies, and withdrawing the offending agent due to toxicity. In the present article, we will review those drugs that are associated with impaired renal function. By focusing on pharmaceutical agents that are currently in clinical practice, we will provide an overview of nephrotoxic drugs that a treating physician is most likely to encounter. In doing so, we will summarize risk factors for nephrotoxicity, describe clinical manifestations, and address preventive and treatment strategies.

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Section: Antifungal Agents Amphotericin Bmentioning

confidence: 99%

Drug-induced impairment of renal function

Pazhayattil¹,

Shirali²

2014

IJNRD

118

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“…Mistro and coworkers (9) systematically reviewed the literature on AmB-induced AKI and assessed whether drug delivery in a locally prepared lipid emulsion or in liposomes reduced nephrotoxicity (9). In their meta-analysis, the authors summarized nine clinical trials comparing AmB in 5% dextrose with AmB in lipid emulsion and found an overall incidence of nephrotoxicity in 30.6% versus 12.2% of cases, respectively.…”

mentioning

confidence: 99%

Incidence, Predictors, and Impact on Hospital Mortality of Amphotericin B Nephrotoxicity Defined Using Newer Acute Kidney Injury Diagnostic Criteria

Rocha

Kobayashi

Almeida

et al. 2015

Antimicrob Agents Chemother

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bStudies on amphotericin B (AmB) nephrotoxicity use diverse definitions of acute kidney injury (AKI). Here, we used the new Kidney Disease Improving Global Outcome (KDIGO) system to describe the incidence, predictors, and impact of AmB-induced AKI on hospital mortality in 162 patients treated with AmB (120 with deoxycholate preparation and 42 with liposomal preparation). KDIGO stage 1 requires an absolute increase of >0.3 mg/dl or >1.5؋ over baseline serum creatinine (SCr), while stage 2 requires >2؋, and stage 3 requires >3؋. A binary KDIGO definition (KDIGObin) corresponds to stage >1. For comparison, we included two definitions of AKI traditionally utilized in nephrotoxicity studies: >0.5 mg/dl (NT0.5) and >2؋ (NT2؋) increase in baseline SCr. The overall incidence of AmB-induced AKI by KDIGObin was 58.6% (stage 1, 30.9%; stage 2, 18.5%; stage 3, 9.3%). Predictors of AKI by KDIGObin were older age and use of furosemide and angiotensin-converting enzyme inhibitor (ACE-I). Traditional criteria detected lower incidences of AKI, at 45.1% (NT0.5) and 27.8% (NT2؋). Predictors of AKI by traditional criteria were older age and use of vancomycin (NT0.5) and use of vancomycin and vasopressors (NT2؋). KDIGObin detected AKI 2 days earlier than the most sensitive traditional criterion. However, only traditional criteria were associated with intensive care unit (ICU) admission, mechanical ventilation, and mortality. In conclusion, the increase in sensitivity of KDIGObin is accompanied by a loss of specificity and ability to predict outcomes. Prospective studies are required to weigh the potential gain from early AKI detection against the potential loss from undue changes in management in patients with subtle elevations in SCr.A mphotericin B (AmB) is a powerful antifungal and antiparasitic agent that binds to the ergosterol component of microbial membranes, creating pores that result in cation leakage and cell death (1). AmB is the drug of choice for the treatment of severe forms of leishmaniasis and remains a lifesaving option for certain invasive fungal infections. Nevertheless, its use is limited by toxicity, including acute kidney injury (AKI).AmB administration leads to direct renal vasoconstriction and causes a profound reduction in renal blood flow (2-4). In addition, AmB alters renal tubular cell membrane permeability (5, 6), allowing back diffusion of hydrogen ions and thereby impairing acid excretion. Recent data suggest that sodium entry through membrane pores activates mitogen-activated protein (MAP) kinases and increases intracellular calcium concentration, culminating in renal tubular cell injury (7). Therefore, AmB-induced AKI appears to result from a combination of ischemic and toxic insults (8). Phenotypically, AmB-induced AKI manifests itself through elevated serum creatinine (SCr) levels that may be accompanied by renal tubular acidosis, characterized by hyperchloremic metabolic acidosis, hypokalemia, and hypomagnesemia.Mistro and coworkers (9) systematically reviewed the literature on AmB-induced AKI and...

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“…The high rate of nephrotoxicity has led to the development of AmB formulations in three different lipid bases: lipid complex, colloidal dispersion, and liposomal [21]. While lipid formulations of AmB were found to be less nephrotoxic than other formulations of the drug, these formulations do not completely eliminate nephrotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of N-acetylcysteine in preventing amphotericin B induced acute kidney injury

Şengel¹,

Tigen²,

Toptaş³

et al. 2016

MMJ

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Objectives: Previously, in an animal study we showed that N-acetylcysteine (NAC) could decrease deoxycholate amphotericin B (DAmB) induced renal tubular apoptosis. In this clinical study, we aimed to evaluate the efficacy of NAC in preventing acute kidney injury (AKI) in febrile neutropenic patients with invasive pulmonary aspergillosis treated with DAmB. Patients and Methods:Thirty-three patients were included in the study. 17 patients were randomly placed into the DAmB group and 16 were randomly placed into the DAmB plus NAC group. Results:The characteristics of patients, durations and cumulative doses of DAmB, concurrent nephrotoxic drugs and basal serum creatinine (SCr) levels of patients were similar. Occurrence of a 1.5 fold or greater increase in the concentration of basal SCr and serum electrolytes were observed prospectively. The overall AKI was found in 13 patients (76.4%) in DAmB group and 6 patients (37.5%) in combination group (P = 0.024). No significant difference was observed in hypokalemia incidence between the groups (87.5 % in combination vs. 94.1 % in DAmB only groups). Conclusion:This clinical pilot study showed that NAC may be a promising anti-oxidant agent to decrease DAmB-induced AKI in febrile neutropenic patients. Bulgular:Hastaların karakteristik özellikleri, DAmB tedavi süreleri ve kümülatif dozları, ek olarak aldıkları nefrotoksik ilaç ve bazal serum kreatinin (SCr) değerleri benzer bulundu. Bazal SCr değerlerinde 1.5 kat veya daha fazla artış ve serum elektrolitleri prospektif olarak gözlemlendi. ABH, DAmB grubunda 13 hastada ( %76,4), kombine grupta 6 hastada (%37,5) görüldü (P = 0,024). İki grup arasında hipokalemi insidansında anlamlı fark saptanmadı (Kombine grupta % 87,5, DAmB grubunda % 94,1).Sonuç: Bu klinik pilot çalışma, NAC'in febril nötropenik hastalarda, DAmB ilişkili ABH'nı azaltmada umut vaad eden bir antioksidan ajan olduğunu göstermektedir.

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Does Lipid Emulsion Reduce Amphotericin B Nephrotoxicity? A Systematic Review and Meta-analysis

Cited by 77 publications

References 9 publications

Drug-induced impairment of renal function

Drug-induced impairment of renal function

Incidence, Predictors, and Impact on Hospital Mortality of Amphotericin B Nephrotoxicity Defined Using Newer Acute Kidney Injury Diagnostic Criteria

Efficacy of N-acetylcysteine in preventing amphotericin B induced acute kidney injury

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