Journal of Research in Pharmacy Practice

Pentoxifylline in Prevention of Amphotericin B-induced Nephrotoxicity and Electrolyte Abnormalities

Document Type : Original Article

Authors

. Mahsa Panahi‑Shokouh 1
. Azadeh Moghaddas 1
. Shirinsadat Badri 2
. Saeedeh Jabalameli 1
. Mahnaz Momenzadeh 1
. Valiollah Mehrzad 3
. Farzaneh Ashrafi 3

1 Department of Clinical Pharmacy and Pharmacy Practice, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Clinical Pharmacy and Pharmacy Practice, Isfahan University of Medical Sciences, Isfahan, Iran Isfahan Kidney Diseases Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

3 Department of Oncology/ Hematology, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract
Objective: Amphotericin B is an antifungal agent used to treat serious fungal 
infections mainly in critically ill patients. Despite its adverse effects including 
renal toxicity and electrolyte imbalances, amphotericin B remains one of the best 
choices for antifungal treatment. Information from animal studies has provided a 
strong scientific basis for the use of pentoxifylline as lowering nephroprotective 
agent. The present study was designed to evaluate the efficacy of pentoxifylline in 
preventing renal toxicity and electrolytes imbalances induced by amphotericin B. 
Methods: This study was conducted as a randomized controlled trial on 44 patients 
admitted to Sayyedoshohada Hospital, Isfahan, Iran, from October 2016 to August 
2018. Patients were assigned to one of the two groups: Pentoxifylline, 400 mg 
twice a day, or matching placebo, from the 1st day of amphotericin B therapy till 
minimum of 7 days. All patients’ information including lab data (serum and urine 
levels of Mg, Na, and K, serum creatinine level, blood urea nitrogen [BUN] and 
urinary creatinine excretion) were gathered at the time of drug initiation and during 
the study period. The results were analyzed by SPSS v. 20 software and Repeated 
measures test was used to assess the differences between groups Findings: This 
study did not show any significant differences between the two groups in terms of 
all the assessed variables, including serum and urinary levels of electrolytes, and 
creatinine, as well as the number of cases presented acute kidney injury during 
the study period. Conclusion: Despite the positive effects of pentoxifylline in 
preventing renal complications in previous studies, this study could not show a 
definitive result in salt wasting or renal damage induced by amphotericin B. So, 
Designing robust studies with more included samples would be valuable.

Keywords

Amphotericin B
electrolytes imbalance
nephrotoxicity
Pentoxifylline
1. Fanos V, Cataldi L. Amphotericin B-induced nephrotoxicity: 
A review. J Chemother 2000;12:463-70.
2. Laniado-Laborín R, Cabrales-Vargas MN. Amphotericin B: Side 
effects and toxicity. Rev Iberoam Micol 2009;26:223‑7.
3. Ulozas E. Amphotericin B-induced nephrotoxicity. Compr 
Toxicol 2010;7:347-57.
4. Gallis HA, Drew RH, Pickard WW. Amphotericin B: 30 years of 
clinical experience. Rev Infect Dis 1990;12:308-29.
5. Harbarth S, Pestotnik SL, Lloyd JF, Burke JP, Samore MH. The 
epidemiology of nephrotoxicity associated with conventional 
amphotericin B therapy. Am J Med 2001;111:528-34.
6. Karimzadeh I, Khalili H, Farsaei S, Dashti-Khavidaki S, 
Sagheb MM. Role of diuretics and lipid formulations in the 
prevention of amphotericin B-induced nephrotoxicity. Eur J Clin 
Pharmacol 2013;69:1351-68.
7. Karimzadeh I, Farsaei S, Khalili H, Dashti-Khavidaki S. Are salt 
loading and prolonging infusion period effective in prevention of 
amphotericin B-induced nephrotoxicity? Expert Opin Drug Saf 2012;11:969-83.
8. Samlaska CP, Winfield EA. Pentoxifylline. J Am Acad Dermatol 
1994;30:603-21.
9. Kreth S, Ledderose C, Luchting B, Weis F, Thiel M. 
Immunomodulatory properties of pentoxifylline are mediated via 
adenosine-dependent pathways. Shock 2010;34:10-6.
10. Heystek HC, Thierry AC, Soulard P, Moulon C. 
Phosphodiesterase 4 inhibitors reduce human dendritic cell 
inflammatory cytokine production and Th1‑polarizing capacity. 
Int Immunol 2003;15:827-35.
11. Nasiri-Toosi Z, Dashti-Khavidaki S, Khalili H, 
Lessan‑Pezeshki M. A review of the potential protective effects 
of pentoxifylline against drug-induced nephrotoxicity. Eur J Clin 
Pharmacol 2013;69:1057-73.
12. Rao KM, Currie MS, McCachren SS, Cohen HJ. 
Pentoxifylline and other methyl xanthines inhibit interleukin-2 
receptor expression in human lymphocytes. Cell Immunol 
1991;135:314-25.
13. Rieckmann P, Weber F, Günther A, Martin S, Bitsch A, 
Broocks A, et al. Pentoxifylline, a phosphodiesterase inhibitor, 
induces immune deviation in patients with multiple sclerosis. 
J Neuroimmunol 1996;64:193-200.
14. Strutz F, Heeg M, Kochsiek T, Siemers G, Zeisberg M, Müller 
GA. Effects of pentoxifylline, pentifylline and gamma‑interferon 
on proliferation, differentiation, and matrix synthesis of human 
renal fibroblasts. Nephrol Dial Transplant 2000;15:1535‑46.
15. Berens KL, Luke DR. Pentoxifylline in the isolated perfused rat 
kidney. Transplantation 1990;49:876-9.
16. Sullivan GW, Carper HT, Mandell GL. Pentoxifylline modulates 
activation of human neutrophils by amphotericin B in vitro. 
Antimicrob Agents Chemother 1992;36:408-16.
17. Bates DW, Su L, Yu DT, Chertow GM, Seger DL, Gomes DR, 
et al. Correlates of acute renal failure in patients receiving 
parenteral amphotericin B. Kidney Int 2001;60:1452-9.
18. Tolins JP, Raij L. Chronic amphotericin B nephrotoxicity in the 
rat: Protective effect of calcium channel blockade. J Am Soc 
Nephrol 1991;2:98-102.
19. Karimzadeh I, Khalili H, Dashti‑Khavidaki S, Sharifian R, 
Abdollahi A, Hasibi M, et al. N-acetyl cysteine in prevention 
of amphotericin-induced electrolytes imbalances: A randomized, 
double-blinded, placebo-controlled, clinical trial. Eur J Clin 
Pharmacol 2014;70:399-408.
20. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D.
A more accurate method to estimate glomerular filtration rate 
from serum creatinine: A new prediction equation. Modification 
of Diet in Renal Disease Study Group. Ann Intern Med 
1999;130(6):461-70.
21. Kidney Disease: Improving Global Outcomes (KDIGO) Acute 
Kidney Injury Work Group. KDIGO Clinical Practice Guideline 
for Acute Kidney Injury. Kidney Int Suppl 2012;2:1.
22. Lin SL, Chen YM, Chiang WC, Tsai TJ, Chen WY. 
Pentoxifylline: A potential therapy for chronic kidney disease. 
Nephrology (Carlton) 2004;9(4):198-204.
23. Lin SL, Chiang WC, Chen YM, Lai CF, Tsai TJ, Hsieh BS. 
The renoprotective potential of pentoxifylline in chronic kidney 
disease. J Chin Med Assoc 2005;68(3):99-105.
24. Chen YM, Lin SL, Chiang WC, Wu KD, Tsai TJ. Pentoxifylline 
ameliorates proteinuria through suppression of renal monocyte 
chemo-attractant protein-1 in patients with proteinuric primary 
glomerular diseases. Kidney Int 2006;69(8):1410-5.
25. Luke DR, Wasan KM, McQueen TJ, Lopez-Berestein G. 
Enhancement of the treatment of experimental candidiasis 
with vascular decongestants. Journal of Infectious Diseases 
1990;162(1):211-4.
26. Wasan K, Vadiei K, Lopez-Berestein G, Verani R, Luke D. 
Pentoxifylline in amphotericin B toxicity rat model. 
Antimicrobial agents and chemotherapy 1990;34(2):241-4.
27. Galindo-Rodríguez G, Bustamante R, Esquivel-Nava G, 
Salazar‑Exaire D, Vela‑Ojeda J, Vadillo‑Buenfil M, et al. 
Pentoxifylline in the treatment of refractory nephrotic syndrome 
secondary to lupus nephritis. J Rheumatol 2003;30:2382-4.
28. Badri S, Dashti-Khavidaki S, Ahmadi F, Mahdavi-Mazdeh M, 
Abbasi MR, Khalili H. Effect of add‑on pentoxifylline on 
proteinuria in membranous glomerulonephritis: A 6-month 
placebo-controlled trial. Clin Drug Investig 2013;33:215-22.
29. Mayer J, Doubek M, Doubek J, Horký D, Scheer P, Stepánek M. 
Reduced nephrotoxicity of conventional amphotericin B therapy 
after minimal nephroprotective measures: Animal experiments 
and clinical study. J Infect Dis 2002;186:379-88.
Journal of Research in Pharmacy Practice
Volume 9, Issue 3
Summer 2020
Pages 135-139

Home

Guide for Authors

Submit Manuscript

Reviewers

Contact Us