A randomized trial with steroids and antithymocyte globulins comparing cyclosporine/azathioprine versus tacrolimus/mycophenolate mofetil (CATM2) in renal transplantation.
BACKGROUND
The best immunosuppressive regimen in benefit-risk ratio in renal transplantation is debated. Nowadays, tacrolimus (Tac) and mycophenolate mofetil (MMF) are considered more efficient than cyclosporine A (CsA) and MMF, but recent studies have challenged this assumption.


METHODS
We conducted a monocentric, prospective, open-labeled, randomized, and controlled trial comparing CsA/azathioprine (Aza) versus Tac/MMF in 289 kidney transplant recipients treated with antithymocyte globulins and prednisone. Primary outcome was the number of patients with clinically suspected acute rejection at 1 year. Secondary outcomes were the number of patients with biopsy-proven acute rejection (BPAR), estimated glomerular filtration rate (eGFR), patient and graft survivals, and adverse events at 1 and 3 years.


RESULTS
During the first year, 21 patients had clinically suspected acute rejection with CsA/Aza (14.4%) vs. 11 (7.7%) with Tac/MMF (P=0.07). BPAR, including borderline, was more frequent in the CsA/Aza group (14.4%) than in the Tac/MMF group (5.6%; P=0.013). At 1 year, patient and graft survivals were not different, and eGFR was 48±1 in the CsA/Aza group and 53±1 mL/min/1.73 m in the Tac/MMF group (P=0.007). There was no significant difference in diabetes after transplantation (16.8% and 18.8%, respectively).


CONCLUSIONS
With antithymocyte globulins and steroids, clinically suspected acute rejections did not differ between CsA/Aza and Tac/MMF arms. Analysis of secondary endpoints showed a lower rate of BPAR, including border line, and a higher eGFR in the Tac/MMF group. CsA/Aza allowed a low acute rejection rate, but Tac/MMF seemed as a better regimen regarding severe secondary outcomes.
APHM, Hôpital de la Conception, Centre de Nephrologie et Transplantation Rénale, Marseille, France. hvacher@ap-hm.fr
Henri
H
Vacher-Coponat
Valerie
V
Moal
Monica
M
Indreies
Raj
R
Purgus
Anderson
A
Loundou
Stephane
S
Burtey
Philippe
P
Brunet
Julie
J
Moussi-Frances
Laurent
L
Daniel
Bertrand
B
Dussol
Yvon
Y
Berland
D000328:Adult; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D001379:Azathioprine / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000453:epidemiology; D015331:Cohort Studies; D016572:Cyclosporine / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000502:physiology; D006084:Graft Rejection / Q000453:epidemiology / Q000517:prevention & control*; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007668:Kidney / Q000502:physiology; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011241:Prednisone / Q000627:therapeutic use; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013256:Steroids / Q000627:therapeutic use*; D016559:Tacrolimus / Q000627:therapeutic use*
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D013256:Steroids; D016572:Cyclosporine; D009173:Mycophenolic Acid; D001379:Azathioprine; D011241:Prednisone; D016559:Tacrolimus