Öz
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.
Anahtar Kelimeler
Amphotericin B Acute kindey injury N-acetylcysteine Febrile neutropenia
Kaynakça
- 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: 10.1056/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: 3100-2. 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: 10.1093/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: 32760. 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. Clin Infect Dis 1999; 29: 1402-7. doi: 10.1086/313498
- 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: 1445-8.
- Bullock WE, Luke RG, Nuttall CE, Bhathena D. Can mannitol reduce amphotericin B nephrotoxicity? Doubleblind 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 low dose 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- 005-0783-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, placebo controlled, 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
Öz
Amaç: Daha önceki bir hayvan çalışmasında, N-asetilsistein (NAC)’in amfoterisin B (DAmB) ilişkili renal tubuler hasarı azalttığını gösterdik. Bu çalışmada, DAmB ile tedavi edilen invaziv pulmoner aspergillozlu febril nötropenik hastalarda NAC’in akut böbrek hasarı (ABH)’nı önlemedeki etkisini göstermeyi amaçladık. Hastalar ve Yöntem: Otuz üç hasta çalışmaya dahil edildi. Randomize olarak 17 hasta DAmB grubuna ve 16 hasta DAmB ve NAC grubuna alındı. Bulgular: Hastaların karakteristik özellikleri, DAmB tedavi süreleri ve kümülatif dozları, ek olarak aldıkları nefrotoksik ilaç ve bazal serum kreatinin (SCr) değerleri benzer bulundu. Bazal SCrdeğerlerinde 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
Anahtar Kelimeler
Amfoterisin B Akut böbrek hasarı N-asetilsistein Febril nötropeni
Kaynakça
- 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: 10.1056/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: 3100-2. 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: 10.1093/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: 32760. 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. Clin Infect Dis 1999; 29: 1402-7. doi: 10.1086/313498
- 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: 1445-8.
- Bullock WE, Luke RG, Nuttall CE, Bhathena D. Can mannitol reduce amphotericin B nephrotoxicity? Doubleblind 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 low dose 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- 005-0783-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, placebo controlled, 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