Abstract
Forty-six children with the nephrotic syndrome whose renal biopsy specimens showed minimal changes and whose response to corticosteroid therapy was unsatisfactory were treated with cyclophosphamide. Three patients were completely steroid-resistant from the outset and the remainder were steroid-dependent. In several patients steroids controlled the condition less effectively with time. Most patients showed signs of steroid toxicity, and growth retardation was striking.
A moderate leucopenia was induced with cyclophosphamide, and treatment was maintained for three to four months in the majority of cases. Thirty-eight children (83%) have remained in complete remission off all treatment for periods of 3 to 23 months, 33 after one course of cyclophosphamide and five after a second course. Two other patients who remitted but relapsed later are still on treatment. In only six patients was full remission not obtained, and three of these were steroid-resistant from the start. Two died from pneumonia and adrenal failure and four continued to have proteinuria, though in one an impressive reduction occurred.
The results indicate that cyclophosphamide therapy is an effective alternative for nephrotic children with normal glomeruli on light microscopy who develop steroid dependence or resistance, and who exhibit toxic effects of steroid therapy.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Adams D. A., Gordon A., Maxwell M. H. Azathioprine treatment of immunological renal disease. JAMA. 1967 Feb 13;199(7):459–463. [PubMed] [Google Scholar]
- Arneil G. C., Lam C. N. Long-term assessment of steroid therapy in childhood nephrosis. Lancet. 1966 Oct 15;2(7468):819–821. doi: 10.1016/s0140-6736(66)92253-7. [DOI] [PubMed] [Google Scholar]
- BLAINEY J. D., BREWER D. B., HARDWICKE J., SOOTHILL J. F. The nephrotic syndrome. Diagnosis by renal biopsy and biochemical and immunological analyses related to the response to steroid therapy. Q J Med. 1960 Apr;29:235–256. [PubMed] [Google Scholar]
- CHASIS H., GOLDRING W., BALDWIN D. S. The effect of nitrogen mustard on renal manifestations of human glomerulonephritis. J Clin Invest. 1950 Jun;29(6):804–804. [PubMed] [Google Scholar]
- COLDBECK J. H. EXPERIENCE WITH ALKYLATING AGENTS IN THE TREATMENT OF CHILDREN WITH THE NEPHROTIC SYNDROME. Med J Aust. 1963 Dec 14;2:987–989. [PubMed] [Google Scholar]
- Cameron J. S., Blandford G. The simple assessment of selectivity in heavy proteinuria. Lancet. 1966 Jul 30;2(7457):242–247. doi: 10.1016/s0140-6736(66)92539-6. [DOI] [PubMed] [Google Scholar]
- Cameron J. S. Histology, protein clearances, and response to treatment in the nephrotic syndrome. Br Med J. 1968 Nov 9;4(5627):352–356. doi: 10.1136/bmj.4.5627.352. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cottom D. G., Newman C. G. Dystonic reactions to phenothiazine derivatives. Arch Dis Child. 1966 Oct;41(219):551–553. doi: 10.1136/adc.41.219.551. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Drummond K. N., Michael A. F., Good R. A., Vernier R. L. The nephrotic syndrome of childhood: immunologic, clinical, and pathologic correlations. J Clin Invest. 1966 Apr;45(4):620–630. doi: 10.1172/JCI105376. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Etteldorf J. N., Roy S., 3rd, Summitt R. L., Sweeney M. J., Wall H. P., Berton W. M. Cyclophosphamide in the treatment of idiopathic lipoid nephrosis. J Pediatr. 1967 May;70(5):758–766. doi: 10.1016/s0022-3476(67)80327-5. [DOI] [PubMed] [Google Scholar]
- FOX M. SUPPRESSION OF TISSUE IMMUNITY BY CYCLOPHOSPHAMIDE. Transplantation. 1964 Jul;2:475–486. doi: 10.1097/00007890-196407000-00004. [DOI] [PubMed] [Google Scholar]
- Grupe W. E., Heymann W. Cytotoxic drugs in steroid-resistant renal disease. Alkylating and antimetabolic agents in the treatment of nephrotic syndrome, lupus nephritis, chronic glomerulonephritis, and purpura nephritis in children. Am J Dis Child. 1966 Nov;112(5):448–458. doi: 10.1001/archpedi.1966.02090140120011. [DOI] [PubMed] [Google Scholar]
- HEYMANN W. Pathogenesis of the nephrotic syndrome: considerations based on clinical and experimental studies. J Pediatr. 1961 May;58:609–619. doi: 10.1016/s0022-3476(61)80112-1. [DOI] [PubMed] [Google Scholar]
- JOACHIM G. R., CAMERON J. S., SCHWARTZ M., BECKER E. L. SELECTIVITY OF PROTEIN EXCRETION IN PATIENTS WITH THE NEPHROTIC SYNDROME. J Clin Invest. 1964 Dec;43:2332–2346. doi: 10.1172/JCI105107. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lagrue G., Bariéty J., Canlorbe P., Vassal J., Milliez P. La chimiothérapie dite immuno-dépressive dans les syndromes néphrotiques primitifs de l'enfant. Presse Med. 1967 Sep 2;75(35):1773–1777. [PubMed] [Google Scholar]
- Marazzini F., Macchi L. Antiblastici e gravidanza. A proposito di un caso trattato prima e durante la gravidanza con ciclofosfamide per neoplasia linfatica maligna e con nascita di un feto vivo e vitale a termine, e seguito da altra gravidanza con esito analogo. Ann Ostet Ginecol Med Perinat. 1966 Nov;88(11):825–834. [PubMed] [Google Scholar]
- PAGE A. R., CONDIE R. M., GOOD R. A. Effect of 6-mercaptopurine on inflammation. Am J Pathol. 1962 May;40:519–530. [PMC free article] [PubMed] [Google Scholar]
- Rubin J. S., Rubin R. T. Cyclophosphamide hemorrhagic cystitis. J Urol. 1966 Sep;96(3):313–316. doi: 10.1016/S0022-5347(17)63260-9. [DOI] [PubMed] [Google Scholar]
- Russell P. J., Hicks J. D. Cyclophosphamide treatment of renal disease in (NZB x NZW) F1 hybrid mice. Lancet. 1968 Mar 2;1(7540):440–441. doi: 10.1016/s0140-6736(68)92778-5. [DOI] [PubMed] [Google Scholar]
- White R. H., Cameron J. S., Trounce J. R. Immunosuppressive therapy in steroid-resistant proliferative glomerulonephritis accompanied by the nephrotic syndrome. Br Med J. 1966 Oct 8;2(5518):853–860. doi: 10.1136/bmj.2.5518.853. [DOI] [PMC free article] [PubMed] [Google Scholar]
- White R. H. Cytotoxic drug therapy in steroid-resistant glomerulonephritis. Proc R Soc Med. 1967 Nov 1;60(11 Pt 1):1164–1168. [PMC free article] [PubMed] [Google Scholar]
- White R. H. Cytotoxic drug therapy in steroid-resistant glomerulonephritis. Proc R Soc Med. 1967 Nov 1;60(11 Pt 1):1164–1168. [PMC free article] [PubMed] [Google Scholar]