Nephrotoxicity induced by amphotericin B deoxycholate in adult patients
DOI:
https://doi.org/10.61182/rnavmed.v11n1a6Keywords:
Amphotericin B deoxycholate, Nephrotoxicity, Adverse drug reactionAbstract
Amphotericin B is a polyene antifungal used to treat invasive fungal infections and leishmaniasis. Its main adverse effect is nephrotoxicity, followed by electrolyte imbalances and infusion-related reactions. To minimize these effects, lipid formulations are recommended; however, due to their high cost, many healthcare systems favor the use of the deoxycholate form. A literature review was conducted across multiple databases to identify factors associated with nephrotoxicity induced by amphotericin B deoxycholate. The most common adverse effects were elevated nitrogenous waste products and hypokalemia, followed by anemia, infusion site pain, and phlebitis. Major risk factors included cumulative drug dose, prolonged treatment duration, advanced age, pharmacological immunosuppression, and concurrent use of other nephrotoxic drugs.
The most effective preventive strategies were aggressive hydration to increase diuresis, electrolyte replacement—particularly potassium supplementation—and, in some cases, discontinuation of the drug.
References
1. Deray G. Amphotericin B nephrotoxicity. J Antimicrob Chemother. 2002;49 Suppl S1:37-41. https://doi.org/10.1093/jac/49.suppl_1.37
2. Messori A, Fadda V, Maratea D, et al. Nephrotoxicity of different formulations of amphotericin B: summarizing evidence by network meta-analysis. Clin Infect Dis. 2013;57(12):1783-4. https://doi.org/10.1093/cid/cit588
3. Sóstenes Mistro, Isis de M. Maciel, Rouseli G. de Menezes. Does lipid emulsion reduce amphotericin B nephrotoxicity? A systematic review and meta-analysis. Clin Infect Dis. 2012;54(12):1774-7. https://doi.org/10.1093/cid/cis290
4. Teixeira Montezuma G, Demarchi Foresto R. Drug-induced nephrotoxicity. Rev Assoc Med Bras. 2020;66(Suppl 1):S82-S90. http://dx.doi.org/10.1590/1806-9282.66.S1.82
5. Calderón-Ospina CA, Guzmán-Ramírez GM, Sarmiento-Monroy JC, Gómez-Angulo DL, et al. Nefrotoxicidad inducida por medicamentos. Médicas UIS. 2011;24(1):73-90. https://revistas.uis.edu.co/index.php/revistamedicasuis/article/view/2583
6. Lai T, Chin-Yen Yeo, Bradley Rockliff. Therapeutic drug monitoring of liposomal amphotericin B in children. Are we there yet? A systematic review. J Antimicrob Chemother. 2024;79:703–711. https://doi.org/10.1093/jac/dkae003
7. Bicanic T, Bottomley C, Loyse A, Brouwer AE, Muzoora C, Taseera K, Jackson A, et al. Toxicity of amphotericin B deoxycholate-based induction therapy in patients with HIV associated cryptococcal meningitis. Antimicrob Agents Chemother. 2015;59:7224–7231. doi:10.1128/AAC.01698-15.
8. Sekiguchi KW, Falcão de Oliveira V, Bridi Cavassin F, Taborda M. A multicentre study of amphotericin B treatment for histoplasmosis: assessing mortality rates and adverse events. J Antimicrob Chemother. 2024;79(7):2598–2606. https://doi.org/10.1093/jac/dkae264
9. Schutz C, Boulware DR, Hupler-Hullsiek K, von Hohenberg M, Rhein J, Taseera K, Thienemann F, Muzoora C, Meya DB, Meintjes G. Acute kidney injury and urinary biomarkers in human immunodeficiency virus-associated cryptococcal meningitis. Open Forum Infect Dis. 2017 Jun 20;4(3):ofx127. https://doi.org/10.1093/ofid/ofx127
10. Assi M, Engracia D, Yakubu I, Gupta G, Kurbanova N, De La Cruz O. Análisis de cohorte retrospectivo de la nefrotoxicidad por anfotericina B en receptores de trasplante renal. Open Forum Infect Dis. 2018 Nov;5(Suppl 1):S341-S342. https://doi.org/10.1093/ofid/ofy210.971
11. Luber AD, Maa L, Minh Lam, Guglielmo BJ. Risk factors for amphotericin B–induced nephrotoxicity. J Antimicrob Chemother. 1999;43(2):267–271. https://doi.org/10.1093/jac/43.2.267
12. Tritle B, Peterson L, Olson J, Benefield E, Cariello PF, Benefield RJ. Liposomal Amphotericin B-associated Nephrotoxicity in Obese and Non-obese Patients. Open Forum Infect Dis. 2019 Oct 23;6(Suppl 2):S714. https://doi.org/10.1093/ofid/ofz360.1789
13. Gakuru J, Kagimu E, Dai B, Okurut S, Nsangi L, et al. Implementation of Single High-dose Liposomal Amphotericin B Based Induction Therapy for Treatment of HIV-associated Cryptococcal Meningitis in Uganda: A Comparative Prospective Cohort Study. Clin Infect Dis. 2025 Feb 24;80(2):417-424. https://doi.org/10.1093/cid/ciae413
14. Garcia G, Pacchini VR, Zamoner W, Balbi AL, Ponce D. Drug-induced acute kidney injury: a cohort study on incidence, identification of pathophysiological mechanisms, and prognostic factors. Front Med. 2024;11:1459170. https://doi.org/10.3389/fmed.2024.1459170
15. Quinteros AR, Fica CA, Abusada AN, Muñoz CL, Novoa MC, Gallardo AC. Uso de anfotericina B deoxicolato y sus reacciones adversas en un hospital universitario en Chile. Rev Chilena Infectol. 2010;27(1):25-33. http://dx.doi.org/10.4067/S0716-10182010000100004
16. Yasrebi-de Kom IAR, Dongelmans DA, Abu-Hanna A, et al. Acute kidney injury associated with nephrotoxic drugs in critically ill patients: a multicenter cohort study using electronic health record data. Clin Kidney J. 2023 Jul 5;16(12):2549-2558. https://doi.org/10.1093/ckj/sfad160
17. Gupta A, Xess I, Soneja M, Keri VC, Sikka K, Siddharth V, Sachdev J, Pandey RM, Kumar A, Wig N, Singh G. Audit for antifungal treatment usage in adults with invasive fungal infection: A prospective observational study. Indian J Med Microbiol. 2025 Jan-Feb;53:100784. https://doi.org/10.1016/j.ijmmb.2024.100784
18. Chatterjee S, Bhattacharjee M, Hazra A, Mukhopadhyay P, Ray BK, Chatterjee S, Dubey S. Pharmacovigilance study of amphotericin B for mucormycosis in post-COVID and non-COVID patients at a tertiary care hospital in Eastern India. Indian J Pharmacol. 2022 Nov-Dec;54(6):417-422. https://doi.org/10.4103/ijp.ijp_474_22
19. Tiwari S, Vakil Z. Reacciones adversas a los antifúngicos utilizados en el tratamiento de la mucormicosis rino-orbitocerebral asociada a la COVID-19. Rev Farmacol Farmacoter. 2022;13(2):197-202. https://doi.org/10.1177/0976500X221105759
20. Kato H, Hagihara M, Yamagishi Y, Shibata Y, Kato Y, Furui T, Watanabe H, Asai N, Koizumi Y, Mikamo H. The evaluation of frequency of nephrotoxicity caused by liposomal amphotericin B. J Infect Chemother. 2018 Sep;24(9):725-728. https://doi.org/10.1016/j.jiac.2018.04.014
21. Meiring S, Fortuin-de Smidt M, Kularatne R, Dawood H, Govender NP; GERMS-SA. Prevalence and hospital management of amphotericin B deoxycholate-related toxicities during treatment of HIV-associated cryptococcal meningitis in South Africa. PLoS Negl Trop Dis. 2016 Jul 28;10(7):e0004865. https://doi.org/10.1371/journal.pntd.0004865
22. Rocha PN, Kobayashi CD, de Carvalho Almeida L, de Oliveira dos Reis C, Santos BM, Glesby MJ. Incidence, predictors, and impact on hospital mortality of amphotericin B nephrotoxicity defined using newer acute kidney injury diagnostic criteria. Antimicrob Agents Chemother. 2015 Aug;59(8):4759-69. https://doi.org/10.1128/AAC.00525-15
23. Geersing TH, Franssen EJ, Spronk PE, van Kan HJM, den Reijer M, van der Voort PHJ. Nephrotoxicity of continuous amphotericin B in critically ill patients with abdominal sepsis: a retrospective analysis with propensity score matching. J Antimicrob Chemother. 2022;77:246-252. https://doi.org/10.1093/jac/dkab372
24. Ibrahim SM, Adlan N, Alomair SM, Butaiban I, Alsalman A, Bawazeer A, Alqahtani M, Mohamed D, Emeka PM. Evaluation of systemic antifungal prescribing knowledge and practice in the critical care setting among ICU physicians and clinical pharmacists: A cross-sectional study. Antibiotics (Basel). 2023 Jan 23;12(2):238. https://doi.org/10.3390/antibiotics12020238
25. Geersing TH, Franssen EJ, Spronk PE, Van Kan HJM, Den Reijer M, Van der Voort PHJ. Nephrotoxicity of continuous amphotericin B in critically ill patients with abdominal sepsis: a retrospective analysis with propensity score matching. J Antimicrob Chemother. 2021;77(1):246-252. https://doi.org/10.1093/jac/dkab372
26. Mayer J, Doubek M, Doubek J, Horky D, Scheer P, Štěpánek M. Reduced nephrotoxicity of conventional amphotericin B therapy after minimal nephroprotective measures: animal experiments and clinical study. J Infect Dis. 2002;186(3):379-88. https://doi.org/10.1086/341662
27. Sridhar S, Ramesh S, Nandini P, Gayatri Jayan, Gangadhara KS. Efficacy of combination therapy of amphotericin and posaconazole in treatment of mucormicosis. J Appl Pharm Res. 2023;11(1):9-14. DOI: 10.18231/j.joapr.2023.11.1.9.14
28. Zurita F, Bombicino D, Estrada C, Núñez G. Insuficiencia renal aguda secundaria a anfotericina B desoxicolato con posterior mejoría de la función renal al rotar a anfotericina B liposomal para el tratamiento de la criptococosis meníngea. A propósito de un caso y revisión de la literatura. Rev Argent Med. 2022;10(3):195-9. http://id.caicyt.gov.ar/ark:/s26184311/fyyfswhia
29. Ríos León OM. Reacciones adversas a la anfotericina B desoxicolato en pacientes VIH (+) con diagnóstico de micosis sistémica en el servicio de Infectología del hospital nacional Edgardo Rebagliati Martins - Lima. Universidad Nacional de Trujillo; 2014. Disponible en: https://hdl.handle.net/20.500.14414/1302
30. Herrera P, Cruz R. Amphotericin B deoxicolate, therapeutic experience in meningeal cryptococcosis in HIV adult patients of Carlos Van Buren Hospital. Boletín Micológico. 2009;24:89-94. Disponible en: https://doi.org/10.22370/bolmicol.2009.24.0.110
31. Botero Aguirre JP, Restrepo Hamid AM. Amphotericin B deoxycholate versus liposomal amphotericin B: effects on kidney function. Cochrane Database Syst Rev. 2015;(11):CD010481. Disponible en: https://doi.org/10.1002/14651858.CD010481.pub2
32. Prieto Yerro C, Vargas Castrillo E, et al. Utilización de anfotericina b no convencional en el hospital clínico de San Carlos. Revista Española Salud Pública. 2000; 74; 35 l-359. http://scielo.isciii.es/scielo.php?script=sci_arttext&pid=S1135-57272000000400005&lng=es&tlng=es
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