Nephrology Dialysis Transplantation, Vol 12, Issue 9 1949-1955, Copyright © 1997 by Oxford University Press
A Beik, R Higgins, F Lam and A Morris
Background. Even in low doses, long-term steroid
immunosuppression is known to cause serious complications. However, the
safety of steroid withdrawal has not been proven in randomized clinical
trials. This study examines donor-specific hyporesponsive transplant
recipients before and after steroid withdrawal, to see if reduction in
immunosuppression was associated with consistent changes in antidonor
immunological reactivity. Methods. Using limiting
dilution assays, the circulating precursor frequency of donor and
third-party-reactive helper T lymphocytes (HTLpf) were determined in 21
consecutive cadaveric renal allograft recipients on standard triple
therapy, before (pre-tx) and at different time points after transplantation
(post-tx). Patients were selected for steroid withdrawal by clinical
criteria (stable graft function and no or only one very mild rejection
episode). Results. Of 21 patients studied, steroids
were successfully withdrawn in nine (steroid withdrawn group, SWG) for at
least 187 days (mean: 380±168.5), and were not withdrawn in 12
patients (steroid continued group, SCG). In the SWG seven of nine patients
developed at least fivefold reduction of post-tx donor-reactive HTLpf
(range 5-17), relative to pre-tx, as compared to two of twelve patients in
the SCG, P=0.01. In both groups, the third-party-reactive HTLpf in most of
these patients remained largely unchanged throughout the study period. In
the SWG, no significant difference of serum creatinine level was found
before and at 6 months after steroid withdrawal (mean: 138±24
versus 132±40, P=0.45).
Conclusions. Patients who developed donor-specific
hyporeactivity as evidenced by low donor-reactive HTLpf had stable graft
function and stable HTLpf levels after complete steroid withdrawal.
Keywords: donor-specific hyporeactivity; limiting
dilution analysis; renal transplantation; steroid withdrawal; T helper
lymphocytes
ORIGINAL ARTICLES
Steroid withdrawal and donor-specific hyporeactivity after cadaveric renal allotransplantation on maintenance triple therapy
Department of Surgery and Renal Unit, Walsgrave Hospital, and Clinical Sciences Laboratory, Department of Biological Sciences, Warwick University, Coventry, UK; Corresponding author at: Clinical Sciences Laboratory, Department of Biological Sciences, Warwick University, Gibbet Hill Road, Coventry CV4 7AL, UK
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