Conversion from cyclosporine to azathioprine at three months reduces the incidence of chronic allograft nephropathy.
BACKGROUND
Conversion from cyclosporine to azathioprine after renal transplantation has been shown to be beneficial in terms of allograft function, cardiovascular risk factor profile, and the incidence of gout. A higher incidence of acute rejection, however, has also been reported and uncertainty still exists about the long-term outcome after conversion. We report on the extended follow-up of an open-label, randomized trial that examined conversion to azathioprine as early as three months after transplantation.


METHODS
One hundred twenty-eight patients were enrolled in this single-center study. Three months after transplantation they were randomly assigned to continue cyclosporine treatment (N = 68), or they were converted to azathioprine (N = 60). The steroid dose was temporarily increased in the patients who were converted.


RESULTS
Patient survival was not different in the two groups. Graft survival tended to be lower (64.7% vs. 76.5% at 15 years) in the cyclosporine continuation group (P = 0.14) when data were analyzed on an intention to treat basis. The graft survival of the patients that stayed on their assigned treatment was significantly higher in the azathioprine arm, starting at two years' post-transplantation. The glomerular filtration rate was significantly higher in the patients who were converted to azathioprine. More allograft biopsies were taken from patients remaining on cyclosporine for suspicion of cyclosporine-related nephrotoxicity and prompted a high rate of late conversions (19%). The relative risk of chronic allograft nephropathy was significantly higher in the group that continued cyclosporine [relative risk, 4.3 (95% CI, 1.4 to 12.9); P = 0.009]. Conversion to azathioprine reduced the need of blood pressure and lipid-lowering drugs.


CONCLUSIONS
Conversion to a calcineurin inhibitor-free immunosuppressive regiment three months after renal transplantation improved allograft function, reduced the need of cardiovascular risk factor-controlling medication, and reduced the incidence of chronic allograft nephropathy.
Bakker
Rene C
RC
Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
Hollander
Adrianus A M J
AA
Mallat
Marko J K
MJ
Bruijn
Jan A
JA
Paul
Leendert C
LC
de Fijter
Johan W
JW
D000328:Adult; D001379:Azathioprine / Q000627:therapeutic use*; D001706:Biopsy; D002318:Cardiovascular Diseases / Q000209:etiology; D002423:Cause of Death; D002908:Chronic Disease; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D007674:Kidney Diseases / Q000517:prevention & control*; D016030:Kidney Transplantation / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000209:etiology; D010349:Patient Compliance; D011507:Proteinuria; D012307:Risk Factors; D016019:Survival Analysis; D013997:Time Factors; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D001379:Azathioprine