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

Year 2016, Volume: 29 Issue: 2, 73 - 78, 01.04.2016

Buket Erturk Sengel Elif Tukenmez Tigen Tayfur Toptas İsik Atagunduz Ayse Tulin Tuglular Mehmet Onder Ergönül Zekaver Odabası

https://doi.org/10.5472/MMJoa.2902.02

Abstract

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.Keywords: Amphotericin

References

  • Von Eiff M, Roos N, Schulten R, Hesse M, Zuhlsdorf M, van de Loo J. Pulmonary aspergillosis: early diagnosis improves survival. Respiration; International Review of Thoracic Diseases 1995; 62: 341-7. doi:10.1159/000196477
  • Wong-Beringer A, Jacobs RA, Guglielmo BJ. Lipid formulations of amphotericin B: clinical efficacy and toxicities. Clin Infect Dis 1998; 27: 603-18. doi: 10.1086/514704
  • Varlam DE, Siddiq MM, Parton LA, Rüssmann H. Apoptosis contributes to amphotericin B-induced nephrotoxicity. Antimicrob Agents Chemother 2001; 45: 679-85. doi: 10.1128/AAC.45.3.679-685.2001
  • Tepel M, van der Giet M, Schwarzfeld C, Laufer U, Liermann D, Zidek W. Prevention of radiographic-contrast-agentinduced reductions in renal function by acetylcysteine. N Engl J Med 2000; 343: 180-4. doi: 0.1056/NEJM200007203430304
  • Marenzi G, Assanelli E, Marana I, et al. N-acetylcysteine and contrast-induced nephropathy in primary angioplasty. N Engl J Med 2006; 354: 2773-82. doi: 10.1056/NEJMoa054209
  • Kay J, Chow WH, Chan TM, et al. Acetylcysteine for prevention of acute deterioration of renal function following elective coronary angiography and intervention: a randomized controlled trial. JAMA 2003; 289: 553-8. doi: 10.1001/
  • jama.289.5.553
  • Odabasi Z, Karaalp A, Cermik H, et al. Reduction of amphotericin B-induced renal tubular apoptosis by N-acetylcysteine. Antimicrob Agents Chemother 2009; 53
  • -2. doi: 10.1128/AAC.00001-09
  • Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis 2011; 52: e56-93. doi
  • 1093/cid/cir073
  • Khwaja A. KDIGO Clinical Practice Guidelines for Acute Kidney Injury. Nephron Clin Pract 2012; 120: c179-84. doi:10.1159/000339789
  • Walsh TJ, Anaissie EJ, Denning DW, et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 2008; 46: 327-60. doi: 10.1086/525258
  • Maertens J, Marchetti O, Herbrecht R, et al. European guidelines for antifungal management in leukemia and hematopoietic stem cell transplant recipients: summary of the ECIL 3--2009 update. Bone Marrow Transplant 2011; 46:709-18. doi: 10.1038/bmt.2010.175
  • Bates DW, Su L, Yu DT, et al. Mortality and costs of acute renal failure associated with amphotericin B therapy. Clin Infect Dis 2001; 32: 686-93. doi: 10.1086/319211
  • Wingard JR, Kubilis P, Lee L, et al. Clinical significance of nephrotoxicity in patients treated with amphotericin B for suspected or proven aspergillosis.
  • Luke RG, Boyle JA. Renal effects of amphotericin B lipid complex. Am J Kidney Dis 1998; 31: 780-5. doi: 10.1016/S0272-6386(98)70046-0
  • Walsh TJ, Finberg RW, Arndt C, et al. Liposomal amphotericin B for empirical therapy in patients with persistent fever and neutropenia. National Institute of Allergy and Infectious Diseases Mycoses Study Group. N Engl J Med 1999; 340: 764-71. doi: 10.1056/NEJM199903113401004
  • Nucci M, Loureiro M, Silveira F, et al. Comparison of the toxicity of amphotericin B in 5% dextrose with that of
  • amphotericin B in fat emulsion in a randomized trial with cancer patients. Antimicrob Agents Chemother 1999; 43
  • -8.
  • Bullock WE, Luke RG, Nuttall CE, Bhathena D. Can mannitol reduce amphotericin B nephrotoxicity? Double blind study and description of a new vascular lesion in kidneys. Antimicrob Agents Chemother 1976; 10: 555-63.
  • doi: 10.1128/AAC.10.3.555
  • Camp MJ, Wingard JR, Gilmore CE, et al. Efficacy of lowdose dopamine in preventing amphotericin B nephrotoxicity in bone marrow transplant patients and leukemia patients.Antimicrob Agents Chemother 1998; 42: 3103-6.
  • Deray G. Amphotericin B nephrotoxicity. J Antimicrob Chemother 2002; 49 Suppl 1: 37-41. doi: 10.1093/jac/49
  • Girmenia C, Cimino G, Di Cristofano F, Micozzi A, Gentile G, Martino P. Effects of hydration with salt repletion on renal toxicity of conventional amphotericin B empirical therapy: a prospective study in patients with hematological malignancies.Support Care Cancer 2005; 13: 987-92. doi: 10.1007/s00520-
  • -0783-x
  • Mistro S, Maciel Ide M, de Menezes RG, Maia ZP, Schooley RT, Badaro R. Does lipid emulsion reduce amphotericin B nephrotoxicity? A systematic review and meta-analysis. Clin Infect Dis 2012; 54: 1774-7. doi: 10.1093/cid/cis290
  • Girmenia C, Gentile G, Micozzi A, Martino P. Nephrotoxicity of amphotericin B desoxycholate. Clin Infect Dis 2001; 33:915-6. doi: 10.1086/322716
  • Fanos V, Cataldi L. Amphotericin B-induced nephrotoxicity: a review. J Chemother 2000; 12: 463-70. doi: 10.1179/joc.2000.12.6.463
  • Karimzadeh I, Khalili H, Dashti-Khavidaki S, et al. N-acetyl cysteine in prevention of amphotericin- induced electrolytes imbalances: a randomized, double-blinded, placebocontrolled, clinical trial. Eur J Clin Pharmacol 2014; 70: 399-408. doi: 10.1007/s00228-014-1642-9
  • Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P, workgroup ADQI. Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 2004; 8: R204-12. doi: 10.1186/cc2872
  • Mehta RL, Kellum JA, Shah SV, et al. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007; 11: R31. doi: 10.1186/cc5713

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

Year 2016, Volume: 29 Issue: 2, 73 - 78, 01.04.2016

Buket Erturk Sengel Elif Tukenmez Tigen Tayfur Toptas İsik Atagunduz Ayse Tulin Tuglular Mehmet Onder Ergönül Zekaver Odabası

https://doi.org/10.5472/MMJoa.2902.02

Abstract

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.Keywords: Amphotericin

Keywords

Amfoterisin B Akut böbrek hasarı N-asetilsistein Febril nötropeni

References

  • Von Eiff M, Roos N, Schulten R, Hesse M, Zuhlsdorf M, van de Loo J. Pulmonary aspergillosis: early diagnosis improves survival. Respiration; International Review of Thoracic Diseases 1995; 62: 341-7. doi:10.1159/000196477
  • Wong-Beringer A, Jacobs RA, Guglielmo BJ. Lipid formulations of amphotericin B: clinical efficacy and toxicities. Clin Infect Dis 1998; 27: 603-18. doi: 10.1086/514704
  • Varlam DE, Siddiq MM, Parton LA, Rüssmann H. Apoptosis contributes to amphotericin B-induced nephrotoxicity. Antimicrob Agents Chemother 2001; 45: 679-85. doi: 10.1128/AAC.45.3.679-685.2001
  • Tepel M, van der Giet M, Schwarzfeld C, Laufer U, Liermann D, Zidek W. Prevention of radiographic-contrast-agentinduced reductions in renal function by acetylcysteine. N Engl J Med 2000; 343: 180-4. doi: 0.1056/NEJM200007203430304
  • Marenzi G, Assanelli E, Marana I, et al. N-acetylcysteine and contrast-induced nephropathy in primary angioplasty. N Engl J Med 2006; 354: 2773-82. doi: 10.1056/NEJMoa054209
  • Kay J, Chow WH, Chan TM, et al. Acetylcysteine for prevention of acute deterioration of renal function following elective coronary angiography and intervention: a randomized controlled trial. JAMA 2003; 289: 553-8. doi: 10.1001/
  • jama.289.5.553
  • Odabasi Z, Karaalp A, Cermik H, et al. Reduction of amphotericin B-induced renal tubular apoptosis by N-acetylcysteine. Antimicrob Agents Chemother 2009; 53
  • -2. doi: 10.1128/AAC.00001-09
  • Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis 2011; 52: e56-93. doi
  • 1093/cid/cir073
  • Khwaja A. KDIGO Clinical Practice Guidelines for Acute Kidney Injury. Nephron Clin Pract 2012; 120: c179-84. doi:10.1159/000339789
  • Walsh TJ, Anaissie EJ, Denning DW, et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 2008; 46: 327-60. doi: 10.1086/525258
  • Maertens J, Marchetti O, Herbrecht R, et al. European guidelines for antifungal management in leukemia and hematopoietic stem cell transplant recipients: summary of the ECIL 3--2009 update. Bone Marrow Transplant 2011; 46:709-18. doi: 10.1038/bmt.2010.175
  • Bates DW, Su L, Yu DT, et al. Mortality and costs of acute renal failure associated with amphotericin B therapy. Clin Infect Dis 2001; 32: 686-93. doi: 10.1086/319211
  • Wingard JR, Kubilis P, Lee L, et al. Clinical significance of nephrotoxicity in patients treated with amphotericin B for suspected or proven aspergillosis.
  • Luke RG, Boyle JA. Renal effects of amphotericin B lipid complex. Am J Kidney Dis 1998; 31: 780-5. doi: 10.1016/S0272-6386(98)70046-0
  • Walsh TJ, Finberg RW, Arndt C, et al. Liposomal amphotericin B for empirical therapy in patients with persistent fever and neutropenia. National Institute of Allergy and Infectious Diseases Mycoses Study Group. N Engl J Med 1999; 340: 764-71. doi: 10.1056/NEJM199903113401004
  • Nucci M, Loureiro M, Silveira F, et al. Comparison of the toxicity of amphotericin B in 5% dextrose with that of
  • amphotericin B in fat emulsion in a randomized trial with cancer patients. Antimicrob Agents Chemother 1999; 43
  • -8.
  • Bullock WE, Luke RG, Nuttall CE, Bhathena D. Can mannitol reduce amphotericin B nephrotoxicity? Double blind study and description of a new vascular lesion in kidneys. Antimicrob Agents Chemother 1976; 10: 555-63.
  • doi: 10.1128/AAC.10.3.555
  • Camp MJ, Wingard JR, Gilmore CE, et al. Efficacy of lowdose dopamine in preventing amphotericin B nephrotoxicity in bone marrow transplant patients and leukemia patients.Antimicrob Agents Chemother 1998; 42: 3103-6.
  • Deray G. Amphotericin B nephrotoxicity. J Antimicrob Chemother 2002; 49 Suppl 1: 37-41. doi: 10.1093/jac/49
  • Girmenia C, Cimino G, Di Cristofano F, Micozzi A, Gentile G, Martino P. Effects of hydration with salt repletion on renal toxicity of conventional amphotericin B empirical therapy: a prospective study in patients with hematological malignancies.Support Care Cancer 2005; 13: 987-92. doi: 10.1007/s00520-
  • -0783-x
  • Mistro S, Maciel Ide M, de Menezes RG, Maia ZP, Schooley RT, Badaro R. Does lipid emulsion reduce amphotericin B nephrotoxicity? A systematic review and meta-analysis. Clin Infect Dis 2012; 54: 1774-7. doi: 10.1093/cid/cis290
  • Girmenia C, Gentile G, Micozzi A, Martino P. Nephrotoxicity of amphotericin B desoxycholate. Clin Infect Dis 2001; 33:915-6. doi: 10.1086/322716
  • Fanos V, Cataldi L. Amphotericin B-induced nephrotoxicity: a review. J Chemother 2000; 12: 463-70. doi: 10.1179/joc.2000.12.6.463
  • Karimzadeh I, Khalili H, Dashti-Khavidaki S, et al. N-acetyl cysteine in prevention of amphotericin- induced electrolytes imbalances: a randomized, double-blinded, placebocontrolled, clinical trial. Eur J Clin Pharmacol 2014; 70: 399-408. doi: 10.1007/s00228-014-1642-9
  • Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P, workgroup ADQI. Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 2004; 8: R204-12. doi: 10.1186/cc2872
  • Mehta RL, Kellum JA, Shah SV, et al. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007; 11: R31. doi: 10.1186/cc5713
There are 33 citations in total.

Details

Subjects Clinical Sciences
Other ID JA93GN75BN
Journal Section Review Makaleler
Authors

Buket Erturk Sengel This is me

Elif Tukenmez Tigen This is me

Tayfur Toptas This is me

İsik Atagunduz This is me

Ayse Tulin Tuglular This is me

Mehmet Onder Ergönül This is me

Zekaver Odabası This is me

Publication Date April 1, 2016
Published in Issue Year 2016 Volume: 29 Issue: 2

Cite

APA Sengel, B. E., Tigen, E. T., Toptas, T., Atagunduz, İ., et al. (2016). Efficacy of N-acetylcysteine in preventing amphotericin B induced acute kidney injury. Marmara Medical Journal, 29(2), 73-78. https://doi.org/10.5472/MMJoa.2902.02
AMA Sengel BE, Tigen ET, Toptas T, Atagunduz İ, Tuglular AT, Ergönül MO, Odabası Z. Efficacy of N-acetylcysteine in preventing amphotericin B induced acute kidney injury. Marmara Med J. April 2016;29(2):73-78. doi:10.5472/MMJoa.2902.02
Chicago Sengel, Buket Erturk, Elif Tukenmez Tigen, Tayfur Toptas, İsik Atagunduz, Ayse Tulin Tuglular, Mehmet Onder Ergönül, and Zekaver Odabası. “Efficacy of N-Acetylcysteine in Preventing Amphotericin B Induced Acute Kidney Injury”. Marmara Medical Journal 29, no. 2 (April 2016): 73-78. https://doi.org/10.5472/MMJoa.2902.02.
EndNote Sengel BE, Tigen ET, Toptas T, Atagunduz İ, Tuglular AT, Ergönül MO, Odabası Z (April 1, 2016) Efficacy of N-acetylcysteine in preventing amphotericin B induced acute kidney injury. Marmara Medical Journal 29 2 73–78.
IEEE B. E. Sengel, E. T. Tigen, T. Toptas, İ. Atagunduz, A. T. Tuglular, M. O. Ergönül, and Z. Odabası, “Efficacy of N-acetylcysteine in preventing amphotericin B induced acute kidney injury”, Marmara Med J, vol. 29, no. 2, pp. 73–78, 2016, doi: 10.5472/MMJoa.2902.02.
ISNAD Sengel, Buket Erturk et al. “Efficacy of N-Acetylcysteine in Preventing Amphotericin B Induced Acute Kidney Injury”. Marmara Medical Journal 29/2 (April 2016), 73-78. https://doi.org/10.5472/MMJoa.2902.02.
JAMA Sengel BE, Tigen ET, Toptas T, Atagunduz İ, Tuglular AT, Ergönül MO, Odabası Z. Efficacy of N-acetylcysteine in preventing amphotericin B induced acute kidney injury. Marmara Med J. 2016;29:73–78.
MLA Sengel, Buket Erturk et al. “Efficacy of N-Acetylcysteine in Preventing Amphotericin B Induced Acute Kidney Injury”. Marmara Medical Journal, vol. 29, no. 2, 2016, pp. 73-78, doi:10.5472/MMJoa.2902.02.
Vancouver Sengel BE, Tigen ET, Toptas T, Atagunduz İ, Tuglular AT, Ergönül MO, Odabası Z. Efficacy of N-acetylcysteine in preventing amphotericin B induced acute kidney injury. Marmara Med J. 2016;29(2):73-8.