The effects of daily cyclophosphamide administration on the development and extent of primary experimental interstitial nephritis in rats

D. Agus, R. Mann, M. Clayman, C. Kelly, L. Michaud, D. Cohn, E. G. Neilson

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

We examined the effects of daily cyclophosphamide administration on the development and extent of tubulointerstitial nephritis produced in rats injected with tubular basement membranes in adjuvant. 15 mg/kg/day of cyclophosphamide completely blocked the development of interstitial lesions, while 2 mg/kg/day enhanced the degree of interstitial injury. When cyclophosphamide in the higher dose was started early in disease, 12 days after immunization, protection from progression was also observed as well as significant reductive improvement. If cyclophosphamide was administered late in disease, 21 days after immunization, no further progression was demonstrable, but substantial injury remained. In the latter two experiments, the beneficial effects of cyclophosphamide could not be explained by a reduction in anti-tubular basement membrane antibodies bound to the kidney. In groups of immunized rats that were tested, however, cyclophosphamide was able to non-specifically impair the delayed-type hypersensitivity response to tubular antigen and PPD. We conclude, therefore, that cyclophosphamide, in high but not low dosage, if given before damage is extensive and prolonged, may successfully inhibit the cellular immune response producing primary interstitial nephritis.

Original languageEnglish (US)
Pages (from-to)635-640
Number of pages6
JournalKidney international
Volume29
Issue number3
DOIs
StatePublished - 1986

ASJC Scopus subject areas

  • Nephrology

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