T. Beveridge et Ry. Calne, CYCLOSPORINE (SANDIMMUN(R)) IN CADAVERIC RENAL-TRANSPLANTATION - 10-YEAR FOLLOW-UP OF A MULTICENTER TRIAL, Transplantation, 59(11), 1995, pp. 1568-1570
Cyclosporine (CsA) was first used clinically as an immunosuppressant i
n organ transplantation 16 years ago (1). While this initial study dem
onstrated the potent immunosuppressive properties of the drug, it also
identified, for the first time, the nephrotoxic side effect which has
influenced the subsequent development of protocols for the use of thi
s agent. As a result of this initial pilot study, a prospective random
ized multicenter trial of CsA monotherapy against azathioprine and ste
roids was undertaken by 8 transplant centers located throughout Europe
. The results from this trial demonstrated the superiority of CsA immu
nosuppression over the ''conventional'' arm (2). With the passage of t
ime, many different CsA protocols, combining CsA with a variety of oth
er immunosuppressants, have been developed and the immunosuppressive v
alue of CsA in organ transplantation has been confirmed repeatedly by
many centers. The major concern now is how best to deploy CsA so as to
limit its nephrotoxicity while retaining its immunosuppressive potenc
y. Debate also surrounds the use of CsA monotherapy compared with comb
ination protocols. In particular, the immunosuppressive value of long-
term adjunctive steroid treatment and whether this is worth the penalt
y of the steroid side effects await clarification. The issue now to be
addressed, therefore, is how best to treat transplant recipients with
a view to obtaining very long-term graft survival with minimal morbid
ity. Thus, those patients selected for that original European multicen
ter trial become a valuable source of information on the long-term eff
ects of CsA therapy. In particular, it allows one to question whether
the nephrotoxic effects of CsA lead to an unacceptable level of toxic
damage to the renal transplant. In addition, the possibility that the
immunosuppressive power of the drug may result in a high incidence of
tumor development can also be investigated in this patient population.
The 8 centers involved in the trial have continued to follow the prog
ress of the patients selected for both arms of the study. This article
describes the result of a 10-year follow-up analysis.