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Effect of Increasing Baseline Immunosuppression on the Prevalence of Clinical and Subclinical Rejection

A Pilot Study

PETER NICKERSON^*,, JOHN JEFFERY^*, JAMES GOUGH, PAUL GRIMM^,§, RACHEL MCKENNA^*,, PATRICIA BIRK^§ and DAVID RUSH^*

^* Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada.
Department of Pathology, University of Manitoba, Winnipeg, Manitoba, Canada.
^§ Department of Pediatrics, University of Manitoba, Winnipeg, Manitoba, Canada.

Correspondence to Dr. Peter Nickerson, Department of Medicine, GG549-820 Sherbrook Street, Winnipeg, Manitoba, Canada, R3A 1R9. Phone: 204-787-7251; Fax: 204-783-6780; E-mail: pnickerson{at}hsc.mb.ca

Abstract

Abstract. This group has reported that treatment of subclinical rejection in the first 3 mo posttransplant with corticosteroids decreases late clinical rejections and improves graft function at 2 yr in renal transplant recipients. The current study was performed to determine whether an increase in baseline immunosuppression would decrease the prevalence of early subclinical rejections, as well as the incidence of early and late clinical rejections. Patients received mycophenolate mofetil (MMF) and Neoral cyclosporin A (CsA) posttransplant (n = 29), of which 17 underwent protocol biopsies at months 1, 2, 3, and 6 (Neoral + MMF Protocol Biopsy [Bx]), while 12 declined protocol biopsies (Neoral + MMF Control). These individuals were compared with 72 historical control patients treated with Sandimmune CsA and Imuran, of which 36 had undergone protocol biopsies at months 1, 2, 3, and 6 (Sandimmune + Azathioprine [AZA] Protocol Bx), and 36 had a protocol biopsy at month 6 (Sandimmune + AZA Control). Baseline immunosuppression with Neoral + MMF decreased the incidence of early clinical rejections (0 to 3 mo) and cumulative corticosteroid exposure, but had no impact on the prevalence of early subclinical rejection. Moreover, to maximally decrease the risk of developing late clinical rejections (months 7 to 12) in Neoral + MMF patients required that protocol biopsies be done and that subclinical rejection be treated. The paradoxical finding of recent clinical trials that a reduction in acute clinical rejection has not improved long-term graft outcome may be explained in part by the failure to control subclinical rejection.

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