Improvement in the outcome of rejection with pentoxifylline in renal transplantation: a randomized controlled trial.
BACKGROUND
Pentoxifylline (PTX), a methylxantine phosphodiesterase inhibitor commonly used to treat peripheral vascular disease, has been shown to decrease the production of proinflammatory cytokines and reactive oxygen species and to reduce the toxic effects of cyclosporine. Thus, administration of PTX to transplant patients, as an adjunct to immunosuppressive therapy, could prevent numerous posttransplantation complications.


METHODS
One hundred forty consecutive patients receiving cadaveric kidney grafts were registered in a randomized double-blind study comparing PTX at a dose of 800 mg/day, then 1200 mg/day, versus placebo during the first 6 months after transplantation. All patients were followed up for 1 year.


RESULTS
Rejection episodes were validated as the only independent risk factor for graft loss in this study. We compared graft survival rates in each group according to the presence or absence of acute rejection. Acute rejection reduced graft survival in the control group (graft survival rate at 1 year, 59% vs. 97%, P < 0.001), but this adverse effect was blunted in the PTX group (72% vs. 89%, NS). This improvement was confirmed by multivariate analysis for risk factors, with graft survival rates being described at best as the interaction between rejection and treatment (PTX vs. placebo, P = 0.045).


CONCLUSIONS
Although PTX does not modify the incidence of any posttransplant complications, it weakens the consequences of rejection on graft survival.
Noel
C
C
Service de Néphrologie-Hémodialyse-Transplantation, Hôpital Calmette, CHRU Lille, France.
Hazzan
M
M
Labalette
M
M
Coppin
M C
MC
Jude
B
B
Dessaint
J P
JP
Lelievre
G
G
D000328:Adult; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000473:pathology / Q000502:physiology; D008297:Male; D015999:Multivariate Analysis; D010431:Pentoxifylline / Q000627:therapeutic use*; D010919:Placebos; D011183:Postoperative Complications / Q000453:epidemiology*; D015203:Reproducibility of Results; D012307:Risk Factors; D013997:Time Factors; D014665:Vasodilator Agents / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D010919:Placebos; D014665:Vasodilator Agents; D010431:Pentoxifylline