Superior outcomes in renal transplantation after early cyclosporine withdrawal and sirolimus maintenance therapy, regardless of baseline renal function.
BACKGROUND
It has become increasingly important to refine therapeutic strategies according to individual patient characteristics. We evaluated the long-term impact of renal function at the time of withdrawing cyclosporine (CsA) in renal allograft recipients receiving sirolimus (SRL), CsA, and steroids (ST).


METHODS
At 3 months+/-2 weeks, 430 of 525 patients were eligible to be randomized to remain on triple-therapy (SRL-CsA-ST, n=215) or to have CsA withdrawn (SRL-ST, n=215). Patients were divided into quartiles according to their baseline (last value before randomization) calculated GFR: <or=45 ml/min (quartile 1, n=104), >45 to 56 ml/min (quartile 2, n=105), >56 to 67 ml/min (quartile 3, n=112), and >67 ml/min (quartile 4, n=107). All data were included (ITT analysis).


RESULTS
At 4 years, calculated GFR for SRL-CsA-ST vs. SRL-ST was 22.1 vs. 37.7 ml/min (P=0.017), 38.6 vs. 56.6 ml/min (P<0.001), 50.7 vs. 66.8 ml/min (P=0.006), and 62.7 vs. 71.4 ml/min (P=0.436), for quartiles 1 to 4, respectively. Death-censored graft loss ranged from 21.2% vs. 7.7% (SRL-CsA-ST vs. SRL-ST, P=0.092) in quartile 1 to 5.5% vs. 1.9% (P=0.618) in quartile 4. The incidence of death and biopsy-confirmed acute rejection also decreased with increasing baseline GFR, but was not significantly different between treatments. Overall, more patients remained on therapy in the SRL-ST group (46.3% vs. 57.9%, P=0.020).


CONCLUSIONS
Early and complete withdrawal of CsA from a combination of SRL, CsA, and steroids was preferable to continuing on this regimen, regardless of baseline renal function. The benefit was most marked in patients with a baseline calculated GFR<or=45 ml/min.
Russ
Graeme
G
The Queen Elizabeth Hospital, Woodville, South Australia, Australia., and Hospitais da Universidade de Coimbra, Coimbra, Portugal. graeme.russ@nwahs.sa.gov.au
Segoloni
Giuseppe
G
Oberbauer
Rainer
R
Legendre
Christophe
C
Mota
Alfredo
A
Eris
Josette
J
Grinyó
Josep M
JM
Friend
Peter
P
Lawen
Joseph
J
Hartmann
Anders
A
Schena
Francesco P
FP
Lelong
Magali
M
Burke
James T
JT
Neylan
John F
JF
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000453:epidemiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D015994:Incidence; D007668:Kidney / Q000503:physiopathology*; D016030:Kidney Transplantation / Q000276:immunology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D020123:Sirolimus / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D013256:Steroids / Q000627:therapeutic use; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D013256:Steroids; D016572:Cyclosporine; D020123:Sirolimus