Long-term results of a randomized study comparing three immunosuppressive schedules with cyclosporine in cadaveric kidney transplantation.
In this randomized controlled trial started in October 1990, 354 cadaveric kidney transplant recipients were assigned to receive either cyclosporine (CsA) monotherapy (115 patients), CsA + steroids (117 patients), or CsA + steroids + azathioprine (122 patients). The median follow-up was 85.1 mo. Thirty-one deaths occurred (infection, 12; cardiovascular disease, 11; neoplasia, 4; and others, 4), and 65 grafts were lost, mostly due to acute (15) or chronic rejection (50). The cumulative graft half-life was 18.1 yr. According to the "intention-to-treat," the 9-yr actuarial patient and graft survival were 94.0% and 73.3%, respectively, in monotherapy, 87.3% and 65.9% in dual therapy, and 87% and 72.2% in triple therapy (P = 0.647). At the last follow-up, the percentage of patients who remained with the original treatment was 51.2% in monotherapy, 81.7% in dual therapy, and 63.3% in triple therapy. At the seventh year, the mean creatinine clearances were 54.9 +/- 17.6 ml/min in monotherapy, 57.9 +/- 23.4 in dual therapy, and 60.6 +/- 20.7 in triple therapy (P = 0.375). Cataracts (P = 0.000), osteoporosis (P = 0.000), and cardiovascular complications (P = 0.000) were more frequent in dual or triple therapy than in monotherapy. Actuarial graft survival at 9 yr in patients on monotherapy who had to have steroids added was similar to that of the other two groups (62.2% versus 69.3%, P = 0.134). In conclusion, actuarial patient and graft survivals did not differ among the three schemes. The long-term renal function and survival were not affected in the patients on monotherapy who needed the addition of steroids. Monotherapy was associated with a lower incidence of extrarenal complications than the other two regimens.
Montagnino
Giuseppe
G
Divisione di Nefrologia e Dialisi IRCCS Ospedale Maggiore, Milan, Italy.
Tarantino
Antonio
A
Divisione di Nefrologia e Dialisi IRCCS Ospedale Maggiore, Milan, Italy.
Segoloni
Giuseppe P
GP
Divisione di Nefrologia e Dialisi, A.O.S. Giovanni Battista, Turin, Italy.
Cambi
Vincenzo
V
Cattedra di Nefrologia Università di Parma, Parma, Italy.
Rizzo
Gaetano
G
U.O. Nefrologia e Trapianti, Ospedale S. Chiara, Pisa, Italy.
Altieri
Paolo
P
Divisione di Nefrologia e Dialisi, Ospedale Brotzu, Cagliari, Italy.
Castagneto
Marco
M
Cattedra di Chirurgia Sostitutiva e del Trapianto d'Organo, Università Cattolica, Rome, Italy.
Salvadori
Maurizio
M
Divisione di Nefrologia e Dialisi, Policlinico Careggi, Firenze, Italy.
Cossu
Maria
M
Divisione di Nefrologia e Dialisi, Ospedale Civile, Sassari, Italy.
Pisani
Francesco
F
Università di "Tor Vergata" and Divisione di Clinica Chirurgica, Ospedale S. Eugenio, Rome (FP), Italy.
Carmellini
Mario
M
Istituto di Scienze Chirurgiche, Università di Siena, Siena, Italy.
Mastrangelo
Francesco
F
Divisione di Nefrologia e Dialisi, Ospedale Fazzi, Lecce, Italy.
Ferrara
Roberto
R
Novartis Farma SpA, Origgio, Italy.
Ponticelli
Claudio
C
Divisione di Nefrologia e Dialisi IRCCS Ospedale Maggiore, Milan, Italy.
D000293:Adolescent; D000328:Adult; D000368:Aged; D001379:Azathioprine / Q000009:adverse effects / Q000627:therapeutic use; D002102:Cadaver; D003401:Creatine / Q000378:metabolism; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000401:mortality; D008137:Longitudinal Studies; D008875:Middle Aged; D013256:Steroids / Q000009:adverse effects / Q000627:therapeutic use; D016019:Survival Analysis; D013997:Time Factors
D007166:Immunosuppressive Agents; D013256:Steroids; D016572:Cyclosporine; D001379:Azathioprine; D003401:Creatine