Skip to main content
SpringerLink
Log in

Prevention of amphotericin-B-induced nephrotoxicity by loading with sodium chloride: A report of 1291 days of treatment with amphotericin B without renal failure

  • Originals
  • Published:
Klinische Wochenschrift Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

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

  1. Andrioli TE, Mohahan M (1968) The interaction of polyene antibiotics with thin lipid membranes. J Gen Physiol 52:300–325

    Google Scholar 

  2. 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

    Google Scholar 

  3. 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

    Google Scholar 

  4. 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

    Google Scholar 

  5. 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

    Google Scholar 

  6. 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

    Google Scholar 

  7. 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

    Google Scholar 

  8. Burgess JL, Birchall R (1972) Nephrotoxicity of amphotericin B, with emphasis on changes in tubular function. Am J Med 53:77–84

    Google Scholar 

  9. 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

    Google Scholar 

  10. Curry CR, Quie PG (1971) Fungal septicemia in patients receiving parenteral hyperalimentation. N Engl J Med 285:1221–1225

    Google Scholar 

  11. 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

    Google Scholar 

  12. Feely J, Heidemann H, Gerkens J, Roberts LJ, Branch RA (1981) Sodium depletion enhances nephrotoxicity of amphotericin B. Lancet I:1422–1423

    Google Scholar 

  13. Fields BT, Bates JH, Abernathy RS (1970) Amphotericin B serum concentrations during therapy. Appl Microbiol 19:955–959

    Google Scholar 

  14. 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

    Google Scholar 

  15. 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

    Google Scholar 

  16. Hawkins C, Armstrong D (1984) Fungal infections in the immunocompromised host. Clin Haematol 13:599–630

    Google Scholar 

  17. 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

    Google Scholar 

  18. 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

    Google Scholar 

  19. Heidemann H, Brune KH (1987) Verhinderung der Amphotericin-B-induzierten Nephrotoxizität durch parenteral verabreichtes Flucytosin. Therapiewoche 37:4158–4166

    Google Scholar 

  20. 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

    Google Scholar 

  21. 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

    Google Scholar 

  22. Lampen JO, Arnow PM, Safferman RS (1960) Mechanisms of protection by sterols against polyene antibiotics. J Bacteriol 80:200–211

    Google Scholar 

  23. 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

    Google Scholar 

  24. Mandell GL, Douglas RG Jr, Bennett JR (1985) Principles and practice of infectious diseases (2nd edn). Wiley, New York

    Google Scholar 

  25. Medoff G, Kobayashi GS (1980) Strategies in the treatment of systemic fungal infections. N Engl J Med 302:145–155

    Google Scholar 

  26. Meunier-Carpentier F, Kiehn TE, Armstrong D (1981) Fungemia in the immunocompromised host. Changing patterns, antigenemia, high mortality. Am J Med 71:363–370

    Google Scholar 

  27. 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

    Google Scholar 

  28. Osswald H, Hermes HH, Nabakowski G (1982) Role of adenosine in signal transmission of tubuloglomerular feedback. Kidney Int 22:136–142

    Google Scholar 

  29. Paul-Ehrlich-Gesellschaft Study Group (1985) Intervention therapy for infections in immunocompromised patients. Z Antimikr Antineoplast Chemother 3:127–206

    Google Scholar 

  30. 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

    Google Scholar 

  31. 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

    Google Scholar 

  32. Simon C, Stille W (1985) Antibiotika-Therapie in Klinik und Praxis (6. Aufl.). Schattauer, Stuttgart New York

    Google Scholar 

  33. 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

    Google Scholar 

  34. 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

    Google Scholar 

  35. 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

    Google Scholar 

  36. 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

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medizinische Klinik und Poliklinik, Abteilung für Hämatologie, Onkologie und Klinische Immunologie, Heinrich-Heine-Universität Düsseldorf, Germany

    M. Arning & R. E. Scharf

  2. Dept. of Basic and Clinical Research, BCR-5, Scripps Clinic and Research Foundation, 10666 North Torrey Pines Road, 92037, La Jolla, California, USA

    R. E. Scharf

Authors
  1. M. Arning
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. E. Scharf
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01727003

Key words

Search

Navigation