Summary
An open, prospective study was performed to evaluate the clinical usefulness of sodium chloride loading for prevention of amphotericin-B-induced nephrotoxicity in 37 patients requiring 44 courses of amphotericin B treatment. The median duration of the treatment course was 22 days (range, 9–136 days), and mean cumulative dose per patient was 1117 mg (range, 231–7831 mg). During amphotericin B treatment, all patients received 50 to 100 ml of 10% sodium chloride (85 to 171 mmol NaCl) via an intravenous line for prevention of amphotericin-B-induced nephrotoxicity evaluated by serum creatinine levels. Using this regimen, none of the patients developed significant nephrotoxicity (increase in serum creatinine of more than twice baseline level, or serum creatinine level ≥2.0 mg/dl, respectively) despite the co-administration of other potentially nephrotoxic drugs. It was not necessary to discontinue treatment with amphotericin B in any of the patients. There were no side effects due to sodium chloride loading. Our results demonstrate that sodium chloride loading is useful for the prevention of amphotericin-B-induced nephrotoxicity.
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Abbreviations
- acla:
-
aclacinomycin
- ALL:
-
acute lymphoblastic leukemia
- ami:
-
aminoglycoside
- AML:
-
acute myeloid leukemia
- BMFT:
-
Bundesministerium für Forschung und Technologie
- BUN:
-
blood urea nitrogen
- ce:
-
cephalosporin
- Co/Imu:
-
cortison/Imurek
- GFR:
-
glomerular filtration rate
- HAM:
-
high-dose cytosine arabinoside and mitoxantrone
- imi:
-
imipenem
- ITP:
-
immune thrombocytopenic purpura
- ld-A:
-
low-dose cytosine arabinoside
- NHL:
-
non-Hodgkin's lymphoma
- RAEB:
-
refractory anemia with excess of blasts
- RBF:
-
renal blood flow
- TAD:
-
thioguanine, cytosine arabinoside, daunorubicin
- TGF:
-
tubuloglomerular feedback
- van:
-
vancomycin
References
Andrioli TE, Mohahan M (1968) The interaction of polyene antibiotics with thin lipid membranes. J Gen Physiol 52:300–325
Bennett JE, Dismukes WE, Duma RJ, Medoff G, Sande MA, Gallis H, Leonard J, Fields BT, Bradshaw M, Haywood H, McGee ZA, Cate TR, Cobbs CG, Warner JF, Alling DW (1979) A comparison of amphotericin B alone and combined with flucytosine in the treatment of cryptococcal meningitis. N Engl J Med 301:126–131
Bhatena DB, Bullock WE, Nuttall CE, Luke RG (1978) The effects of amphotericin B therapy on the intrarenal vasculature and renal tubules in man. Clin Nephrol 9:103–110
Boerner U, Szasz G, Bablok W, Busch EW (1979) Referenzwerte für Kreatinin im Serum, ermittelt mit einer spezifischen enzymatischen Methode. J Clin Chem Clin Biochem 17:679–682
Branch RA, Jackson EK, Jacqz E, Stein R, Ray WA, Ohnhaus EE, Meusers P, Heidemann H (1987) Amphotericin B nephrotoxicity in humans decreased by sodium supplements with coadministration of Ticarcillin or intravenous saline. Klin Wochenschr 65:500–506
Büchner T, Urbanitz D, Hiddemann W, Rühl H, Ludwig WD, Fischer J, Aul C, Vaupel HA, Kuse R, Zeile G, Nowrousian MR, König HJ, Walter M, Wendt FC, Sodomann H, Hossfeld K, von Paleske A, Löffler H, Gassmann W, Hellriegel KP, Fülle HH, Lunscken CH, Emmerich B, Pralle H, Pees HW, Pfreundschuh M, Bartels H, Koeppen KM, Schwerdtfeger R, Donhuijsen-Ant R, Mainzer K, Bonfert B, Köppler H, Zurborn KH, Ranft K, Thiel E, Heinecke A (1985) Intensified induction and consolidation with or without maintenance chemotherapy for acute myeloid leukemia (AML). J Clin Oncol 3:1583–1589
Bullock WE, Luke RG, Nuttall CE, Bhatena D (1976) Can mannitol reduce amphotericin B nephrotoxicity? Double-blind study and description of a new vascular lesion in kidneys. Anitmicrob Agents Chemother 10:555–563
Burgess JL, Birchall R (1972) Nephrotoxicity of amphotericin B, with emphasis on changes in tubular function. Am J Med 53:77–84
Butler WT, Bennett JE, Ailing DW, Wertlake PT, Utz JP, Hill GJ (1964) Nephrotoxicity of amphotericin B: early and late effects in 81 patients. Ann Intern Med 61:175–187
Curry CR, Quie PG (1971) Fungal septicemia in patients receiving parenteral hyperalimentation. N Engl J Med 285:1221–1225
Dismukes WE, Cloud G, Gallis HA, Kerkering TM, Medoff G, Craven PC, Kaplowitz LG, Fisher JF, Gregg CR, Bowles CA, Shamody S, Stamm AM, Diasio RB, Kaufman L, Soong SJ, Blackwelder WC, and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (1987) Treatment of cryptococcal meningitis with combination amphotericin B and flucytosine for four as compared with six weeks. N Engl J Med 317:334–341
Feely J, Heidemann H, Gerkens J, Roberts LJ, Branch RA (1981) Sodium depletion enhances nephrotoxicity of amphotericin B. Lancet I:1422–1423
Fields BT, Bates JH, Abernathy RS (1970) Amphotericin B serum concentrations during therapy. Appl Microbiol 19:955–959
Gerkens JF, Branch RA (1980) The influence of sodium status and furosemide on canine acute amphotericin B nephrotoxicity. J Pharm Exp Ther 214:306–311
Gerson SL, Talbot GH, Hurwitz S, Strom BL, Lusk EJ, Cassileth PA (1984) Prolonged granulocytopenia. The major risk factor for invasive pulmonary aspergillosis in patients with acute leukemia. Ann Intern Med 100:345–351
Hawkins C, Armstrong D (1984) Fungal infections in the immunocompromised host. Clin Haematol 13:599–630
Helger R, Rindfrey H, Hilgenfeldt J (1974) Eine Methode zur direkten Bestimmung des Kreatinins in Serum und Harn ohne Enteiweissung nach einer modifizierten Jaffé-Methode. Z Klin Chem Klin Biochem 12:344–349
Heidemann H, Gerkens JF, Spickard WA, Jackson E, Branch RA (1983) Amphotericin B nephrotoxicity in humans decreased by salt repletion. Am J Med 75:476–481
Heidemann H, Brune KH (1987) Verhinderung der Amphotericin-B-induzierten Nephrotoxizität durch parenteral verabreichtes Flucytosin. Therapiewoche 37:4158–4166
Hiddemann W, Kreutzmann H, Straif K, Ludwig WD, Mertelsmann R, Donhuijsen-Ant R, Lengfelder E, Arlin Z, Büchner Th (1987) High-dose cytosine arabinoside and mitoxantrone: a highly effective regimen in refractory acute myeloid leukemia. Blood 69:744–749
Hoelzer D, Thiel E, Löffler H, Bodenstein H, Plaumann L, Büchner T, Urbanitz D, Koch P, Heimpel H, Engelhardt R, Müller U, Wendt FC, Sodomann H, Rühl H, Herrmann F, Kaboth W, Dietzfelbinger H, Pralle H, Lunscken Ch, Hellriegel KP, Spors S, Nowrousian RM, Fischer J, Fülle H, Mitrou PS, Pfreundschuh M, Görg Ch, Emmerich B, Queisser W, Meyer P, Labedzki L, Essers U, König H, Mainzer K, Herrmann R, Messerer D, Zwingers T (1988) Intensified therapy in acute lymphoblastic and acute undifferentiated leukemia in adults. Blood 64:38–47
Lampen JO, Arnow PM, Safferman RS (1960) Mechanisms of protection by sterols against polyene antibiotics. J Bacteriol 80:200–211
Maddux MS, Barriere SL (1980) A review of complications of amphotericin B therapy: recommendations for prevention and management. Drug Intel Clin Pharm 14:177–181
Mandell GL, Douglas RG Jr, Bennett JR (1985) Principles and practice of infectious diseases (2nd edn). Wiley, New York
Medoff G, Kobayashi GS (1980) Strategies in the treatment of systemic fungal infections. N Engl J Med 302:145–155
Meunier-Carpentier F, Kiehn TE, Armstrong D (1981) Fungemia in the immunocompromised host. Changing patterns, antigenemia, high mortality. Am J Med 71:363–370
Mitrou PS, Kuse R, Anger H, Herrmann R, Bonfert B, Pralle H, Thiel E, Westerhausen M, Mainzer K, Bartels H, Löffler H (1985) Aclarubicin (Aclacinomycin) in the treatment of relapsing acute leukemia. Eur J Cancer Clin Oncol 21:919–929
Osswald H, Hermes HH, Nabakowski G (1982) Role of adenosine in signal transmission of tubuloglomerular feedback. Kidney Int 22:136–142
Paul-Ehrlich-Gesellschaft Study Group (1985) Intervention therapy for infections in immunocompromised patients. Z Antimikr Antineoplast Chemother 3:127–206
Pizzo PA, Robichaud KJ, Gill FA, Witebsky FG (1982) Empiric antibiotic and antifungal therapy for cancer patients with prolonged fever and granulocytopenia. Am J Med 72:101–111
Rhoades EG, Ginn HE, Muchmore HG, Smith WO, Hammarsten JF (1961) Effect of amphotericin B upon renal function in man. In: Gray P, Tabenkin B, Bradley SG (eds) Antimicrobiology agents annual 1960. Plenum Press, New York, pp 539–542
Simon C, Stille W (1985) Antibiotika-Therapie in Klinik und Praxis (6. Aufl.). Schattauer, Stuttgart New York
Szasz G, Boerner U, Busch EW, Bablok W (1979) Enzymatische Kreatinin-Bestimmung im Serum: Vergleich mit Jaffé-Methoden. J Clin Chem Clin Biochem 17:679–682
Stamm AM, Diasio RB, Dismukes WE (1987) Toxicity of amphotericin B plus flucytosine in 194 patients with cryptococcal meningitis. Am J Med 83:236–242
Weh HJ, Zschaber R, Hossfeld DK (1984) Low-dose cytosine arabinoside in the treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Blut 48:239–242
van Zuthphen H, van Deenen LLM, Kinsky SC (1966) The action of polyene antibiotics on bilayer lipid membranes. Biochem Biophys Res Commun 22:393–399
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Arning, M., Scharf, R.E. Prevention of amphotericin-B-induced nephrotoxicity by loading with sodium chloride: A report of 1291 days of treatment with amphotericin B without renal failure. Klin Wochenschr 67, 1020–1028 (1989). https://doi.org/10.1007/BF01727003
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DOI: https://doi.org/10.1007/BF01727003