Studies on the survival of simultaneous canine renal and segmental pancreatic allografts

Walter Severyn, Les Olson, Joshua Miller, George Kyriakides, Alex Rabinovitch, Cathy Flaa, Daniel Mintz*

*Corresponding author for this work

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Prolonged survival of the vascularized free-draining intraperitoneal pancreatic segmental allografts (FDPS) has been observed previously in immunosuppressed beagle littermates matched for low mixed lymphocyte culture (MLC) reactivity. When rejection (hyperglycemia) did occur, it was abrupt, unpredictable, and irreversible. This contrasts with renal allograft rejection in which elevations of serum creatinine are reversible with increased immunosuppression. In the present experiments, low MLC-reactive littermate pairs underwent simultaneous transplantation of kidney and FDPS allografts from the same donor. Increases in serum creatinine from 0.5 mg/dl to 1.5 mg/dl (renal rejection) occurred 4 to 5 days after transplantation (mean = 20.5 ± 4.1) and preceded the onset of hyperglycemia by 6 to 22 days (mean = 10.6 ± 4.6) in nonimmunosuppressed animals. At the onset of kidney rejection but before hyperglycemia developed, renal allograft biopsies revealed generalized mononuclear infiltration, while FDPS biopsies showed diffuse interstitial infiltration, but islets of Langerhans appeared to be spared. Treatment intervention with azathioprine and corticosteroids at the time of creatinine elevation prevented the onset of hyperglycemia from 46 to >260 days in four of nine animals. Biopsies after 2 weeks of therapy showed resolution of the lymphoid infiltrates in the kidney and limitation of infiltrates to perivascular areas in the FDPS allografts. Immunological monitoring of peripheral blood lymphocyte function demonstrated the development of positive in vitro cell-mediated lymphocytoxicity shortly before the onset of hyperglycemia but only after creatinine elevation was well established and biopsies revealed evidence of rejection in both the renal and FDPS allografts.

Original languageEnglish (US)
Pages (from-to)606-612
Number of pages7
JournalTransplantation
Volume33
Issue number6
DOIs
StatePublished - Jan 1 1982

ASJC Scopus subject areas

  • Transplantation

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