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. 1990 Jul;65(7):732–738. doi: 10.1136/adc.65.7.732

Nephrotoxicity after ifosfamide.

R Skinner 1, A D Pearson 1, L Price 1, M G Coulthard 1, A W Craft 1
PMCID: PMC1792439  PMID: 2386379

Abstract

Eleven children and adolescents with previously normal renal function who received ifosfamide for the treatment of extrarenal solid tumours underwent detailed investigation of glomerular and renal tubular function to assess the incidence and extent of renal damage. None had received cisplatin. Glomerular filtration rate (measured by plasma clearance of 51Cr labelled edetic acid) was reduced in six children. All 11 patients had evidence of proximal, and six of distal, tubular damage. Proximal tubular toxicity was indicated by phosphaturia and hypophosphataemia (n = 4), glycosuria (n = 5), increased urine beta 2 microglobulin excretion (n = 11), and generalised aminoaciduria (n = 10); distal tubular damage caused a reduction of the osmolality of the urine in an early morning sample. Two children developed clinical hypophosphataemic rickets, and one of these also had severe nephrogenic diabetes insipidus. Glomerular and tubular nephrotoxicity are common and potentially serious complications of ifosfamide treatment in children.

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Selected References

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  1. Antman K. H., Montella D., Rosenbaum C., Schwen M. Phase II trial of ifosfamide with mesna in previously treated metastatic sarcoma. Cancer Treat Rep. 1985 May;69(5):499–504. [PubMed] [Google Scholar]
  2. Branch R. A. Prevention of amphotericin B-induced renal impairment. A review on the use of sodium supplementation. Arch Intern Med. 1988 Nov;148(11):2389–2394. [PubMed] [Google Scholar]
  3. Brodehl J., Gellissen K., Weber H. P. Postnatal development of tubular phosphate reabsorption. Clin Nephrol. 1982 Apr;17(4):163–171. [PubMed] [Google Scholar]
  4. Brodehl J., Krause A., Hoyer P. F. Assessment of maximal tubular phosphate reabsorption: comparison of direct measurement with the nomogram of Bijvoet. Pediatr Nephrol. 1988 Apr;2(2):183–189. doi: 10.1007/BF00862587. [DOI] [PubMed] [Google Scholar]
  5. Cohn S. L., Lincoln S. T., Rosen S. T. Present status of serum tumor markers in diagnosis, prognosis, and evaluation of therapy. Cancer Invest. 1986;4(4):305–327. doi: 10.3109/07357908609017511. [DOI] [PubMed] [Google Scholar]
  6. Davies S. M., Pearson A. D., Craft A. W. Toxicity of high-dose ifosfamide in children. Cancer Chemother Pharmacol. 1989;24 (Suppl 1):S8–10. doi: 10.1007/BF00253229. [DOI] [PubMed] [Google Scholar]
  7. DeFronzo R. A., Abeloff M., Braine H., Humphrey R. L., Davis P. J. Renal dysfunction after treatment with isophosphamide (NSC-109724). Cancer Chemother Rep. 1974 May-Jun;58(3):375–382. [PubMed] [Google Scholar]
  8. Fillastre J. P., Viotte G., Morin J. P., Moulin B. Nephrotoxicity of antitumoral agents. Adv Nephrol Necker Hosp. 1988;17:175–218. [PubMed] [Google Scholar]
  9. Fosså S. D., Talle K. Treatment of metastatic renal cancer with ifosfamide and mesnum with and without irradiation. Cancer Treat Rep. 1980 Oct-Nov;64(10-11):1103–1108. [PubMed] [Google Scholar]
  10. Goren M. P., Wright R. K., Horowitz M. E., Pratt C. B. Ifosfamide-induced subclinical tubular nephrotoxicity despite mesna. Cancer Treat Rep. 1987 Feb;71(2):127–130. [PubMed] [Google Scholar]
  11. Goren M. P., Wright R. K., Pratt C. B., Horowitz M. E., Dodge R. K., Viar M. J., Kovnar E. H. Potentiation of ifosfamide neurotoxicity, hematotoxicity, and tubular nephrotoxicity by prior cis-diamminedichloroplatinum(II) therapy. Cancer Res. 1987 Mar 1;47(5):1457–1460. [PubMed] [Google Scholar]
  12. Hacke M., Schmoll H. J., Alt J. M., Baumann K., Stolte H. Nephrotoxicity of cis-diamminedichloroplatinum with or without ifosfamide in cancer treatment. Clin Physiol Biochem. 1983;1(1):17–26. [PubMed] [Google Scholar]
  13. Hadidi A. H., Coulter C. E., Idle J. R. Phenotypically deficient urinary elimination of carboxyphosphamide after cyclophosphamide administration to cancer patients. Cancer Res. 1988 Sep 15;48(18):5167–5171. [PubMed] [Google Scholar]
  14. Hilgard P., Burkert H. Sodium-2-mercaptoethanesulfonate (MESNA) and ifosfamide nephrotoxicity. Eur J Cancer Clin Oncol. 1984 Nov;20(11):1451–1452. doi: 10.1016/0277-5379(84)90067-1. [DOI] [PubMed] [Google Scholar]
  15. Jung K., Scholz D. An optimized assay of alanine aminopeptidase activity in urine. Clin Chem. 1980 Aug;26(9):1251–1254. [PubMed] [Google Scholar]
  16. Knapp M. L., Hadid O. Investigations into negative interference by jaundiced plasma in kinetic Jaffé methods for plasma creatinine determination. Ann Clin Biochem. 1987 Jan;24(Pt 1):85–97. doi: 10.1177/000456328702400114. [DOI] [PubMed] [Google Scholar]
  17. Magrath I., Sandlund J., Raynor A., Rosenberg S., Arasi V., Miser J. A phase II study of ifosfamide in the treatment of recurrent sarcomas in young people. Cancer Chemother Pharmacol. 1986;18 (Suppl 2):S25–S28. doi: 10.1007/BF00647446. [DOI] [PubMed] [Google Scholar]
  18. Marti C., Kroner T., Remagen W., Berchtold W., Cserhati M., Varini M. High-dose ifosfamide in advanced osteosarcoma. Cancer Treat Rep. 1985 Jan;69(1):115–117. [PubMed] [Google Scholar]
  19. Miser J. S., Kinsella T. J., Triche T. J., Tsokos M., Jarosinski P., Forquer R., Wesley R., Magrath I. Ifosfamide with mesna uroprotection and etoposide: an effective regimen in the treatment of recurrent sarcomas and other tumors of children and young adults. J Clin Oncol. 1987 Aug;5(8):1191–1198. doi: 10.1200/JCO.1987.5.8.1191. [DOI] [PubMed] [Google Scholar]
  20. Moncrieff M. W., Brenton D. P., Arthur L. J. Case of tumour rickets. Arch Dis Child. 1978 Sep;53(9):740–745. doi: 10.1136/adc.53.9.740. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Moncrieff M., Foot A. Fanconi syndrome after ifosfamide. Cancer Chemother Pharmacol. 1989;23(2):121–122. doi: 10.1007/BF00273531. [DOI] [PubMed] [Google Scholar]
  22. Morgan D. B. Assessment of renal tubular function and damage and their clinical significance. Ann Clin Biochem. 1982 Jul;19(Pt 4):307–313. doi: 10.1177/000456328201900422. [DOI] [PubMed] [Google Scholar]
  23. Newbury-Ecob R. A., Noble V. W., Barbor P. R. Ifosfamide-induced Fanconi syndrome. Lancet. 1989 Jun 10;1(8650):1328–1328. doi: 10.1016/s0140-6736(89)92719-0. [DOI] [PubMed] [Google Scholar]
  24. Patterson W. P., Khojasteh A. Ifosfamide-induced renal tubular defects. Cancer. 1989 Feb 15;63(4):649–651. doi: 10.1002/1097-0142(19890215)63:4<649::aid-cncr2820630408>3.0.co;2-z. [DOI] [PubMed] [Google Scholar]
  25. Pinkerton C. R., Rogers H., James C., Bowman A., Barbor P. R., Eden O. B., Pritchard J. A phase II study of ifosfamide in children with recurrent solid tumours. Cancer Chemother Pharmacol. 1985;15(3):258–262. doi: 10.1007/BF00263897. [DOI] [PubMed] [Google Scholar]
  26. Pratt C. B., Horowitz M. E., Meyer W. H., Etcubanas E., Thompson E. I., Douglass E. C., Wilimas J. A., Hayes F. A., Green A. A. Phase II trial of ifosfamide in children with malignant solid tumors. Cancer Treat Rep. 1987 Feb;71(2):131–135. [PubMed] [Google Scholar]
  27. Sangster G., Kaye S. B., Calman K. C., Dalton J. F. Failure of 2-mercaptoethane sulphonate sodium (mesna) to protect against ifosfamide nephrotoxicity. Eur J Cancer Clin Oncol. 1984 Mar;20(3):435–436. doi: 10.1016/0277-5379(84)90093-2. [DOI] [PubMed] [Google Scholar]
  28. Sawyer M. H., Webb D. E., Balow J. E., Straus S. E. Acyclovir-induced renal failure. Clinical course and histology. Am J Med. 1988 Jun;84(6):1067–1071. doi: 10.1016/0002-9343(88)90313-0. [DOI] [PubMed] [Google Scholar]
  29. Skillen A. W., Buamah P. K., Cantwell B. M., Cornell C., Hodson A. W., Harris A. L. Urinary protein and enzyme excretion in patients receiving chemotherapy with the cis-platinum analogs carboplatin (CBDCA, JM8) and iproplatin (CHIP, JM9). Cancer Chemother Pharmacol. 1988;22(3):228–234. doi: 10.1007/BF00273416. [DOI] [PubMed] [Google Scholar]
  30. Skinner R., Pearson A. D., Price L., Cunningham K., Craft A. W. Hypophosphataemic rickets after ifosfamide treatment in children. BMJ. 1989 Jun 10;298(6687):1560–1561. doi: 10.1136/bmj.298.6687.1560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Smeitink J., Verreussel M., Schröder C., Lippens R. Nephrotoxicity associated with ifosfamide. Eur J Pediatr. 1988 Nov;148(2):164–166. doi: 10.1007/BF00445929. [DOI] [PubMed] [Google Scholar]
  32. Van Dyk J. J., Falkson H. C., Van der Merwe A. M., Falkson G. Unexpected toxicity in patients treated with iphosphamide. Cancer Res. 1972 May;32(5):921–924. [PubMed] [Google Scholar]
  33. de Kraker J., Voûte P. A. The role of ifosfamide in paediatric soft tissue sarcomas. Cancer Chemother Pharmacol. 1986;18 (Suppl 2):S23–S24. doi: 10.1007/BF00647445. [DOI] [PubMed] [Google Scholar]

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