Influence of sirolimus on proteinuria in de novo kidney transplantation with expanded criteria donors: comparison of two CNI-free protocols.
BACKGROUND
The contribution of mammalian target of rapamycin (mTOR) inhibitors to proteinuria is controversial. The aim was to analyse proteinuria in suboptimal kidney calcineurin inhibitor-(CNI) free de novo immunosuppression.


METHODS
All patients from our centre with donors >60 years and CNI-free treatment were included (n = 108). Patients were divided into two groups: (i) SRL group: sirolimus (SRL) + prednisone + mycophenolate mofetil (MMF) + antiCD25; (ii) MMF group: prednisone + MMF w/ or w/o antiCD25 (n = 75). Follow-up was 12 months.


RESULTS
Donors were slightly younger in the SRL group (68 vs 71 years; P < 0.05), receptor age (67 vs 65 years) was not significantly different. Patient survival in the MMF group was 88 vs 94% in the SRL group, however, these differences did not reach statistical significance. One-year graft survival censored for death was 83% in the MMF group and 94% in the SRL group. Acute rejection rate was 45% in the MMF and 15% in the SRL group (P < 0.01). The incidence of CNI introduction was higher in the MMF-group (35 vs 5; P < 0.05). The intention-to-treat analysis revealed significant differences of proteinuria [SRL vs MMF at 12 months: 461 (163-6988) vs 270 (53-3029) mg/day], which did not exist in the on-therapy (OT) analysis [SRL vs MMF at 12 months: 357 (199-1428) vs 279 (53-3029) mg/day]. New onset nephrotic range proteinuria seemed to occur slightly more frequently in SRL patients (3/33 vs 1/75; P = 0.049), however, all four cases occurred in a context of recurrent disease, or previous drug-independent damage or non-adherence. All of these patients were converted to CNI.


CONCLUSIONS
SRL-based compared with MMF-based treatment in kidney transplantation with advanced age donors is associated with an acceptable outcome, however, with increased proteinuria in the intention-to-treat analysis. A large subgroup of the patients in the MMF group experienced acute rejection and required conversion to CNI.
Diekmann
Fritz
F
Department of Nephrology and Renal Transplantation, Hospital Clínic, Villarroel, 170, E-08036 Barcelona, Spain. fdiekman@clinic.ub.es
Gutiérrez-Dalmau
Alex
A
López
Sonia
S
Cofán
Federico
F
Esforzado
Núria
N
Ricart
María José
MJ
Rossich
Esther
E
Saval
Núria
N
Torregrosa
José Vicente
JV
Oppenheimer
Federico
F
Campistol
Josep M
JM
D000368:Aged; D065095:Calcineurin Inhibitors; D006085:Graft Survival; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D016030:Kidney Transplantation / Q000009:adverse effects / Q000379:methods*; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D011241:Prednisone / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D011507:Proteinuria / Q000139:chemically induced*; D020123:Sirolimus / Q000009:adverse effects* / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases; D013997:Time Factors
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D009173:Mycophenolic Acid; D011241:Prednisone; D020123:Sirolimus