Everolimus with very low-exposure cyclosporine a in de novo kidney transplantation: a multicenter, randomized, controlled trial.
BACKGROUND
In combination with everolimus (EVL), cyclosporine A (CsA) may be used at low exposure, so reducing the risk of renal dysfunction in renal transplant recipients (RTR). We evaluated whether higher exposure of EVL could allow a further reduction of CsA.


METHODS
De novo RTR were randomized to standard exposure EVL (C0 3-8 ng/mL) with low-concentration CsA (C2 maintenance levels 350-500 ng/mL, group A) or higher EVL exposure (C0 8-12 ng/mL) with very low-concentration CsA (C2 maintenance levels 150-300 ng/mL, group B). The primary endpoints were 6-month creatinine clearance (CrCl) and biopsy-proven acute rejection (BPAR) rate. After 6 months, patients were followed up (observational extension) to 12 months.


RESULTS
Two hundred eighty-five RTR (97% from deceased donors) were enrolled. Two patients per group died (1.4%). The 6-month death-censored graft survival was 90.2% in group A and 97.9% in group B and was unchanged at 12 months (P=0.007). There was no significant difference between groups at 6 months in CrCl (59.9 vs. 57.8 mL/min) and BPAR rates (14.7% vs. 11.9%) and also at 12 months (CrCl 62.5+/-20.7 vs. 61.3+/-22.0 mL/min, BPAR 14.7% vs. 14.1%). No significant differences were seen in treated acute rejections, steroid-resistant acute rejections, treatment failures, or delayed graft function, although there was a trend to better results in group B.


CONCLUSIONS
EVL given at higher exposure for 6 months plus very low CsA concentration may obtain low acute rejection rate and good graft survival in De novo renal transplantation. However, there was no difference between groups in CrCl.
Salvadori
Maurizio
M
Renal Transplant Unit, Careggi University Hospital, Florence, Italy. salvadorim@aou-careggi.toscana.it
Scolari
Maria Piera
MP
Bertoni
Elisabetta
E
Citterio
Franco
F
Rigotti
Paolo
P
Cossu
Maria
M
Dal Canton
Antonio
A
Tisone
Giuseppe
G
Albertazzi
Alberto
A
Pisani
Francesco
F
Gubbiotti
Giampiero
G
Piredda
Gianbenedetto
G
Busnach
Ghil
G
Sparacino
Vito
V
Goepel
Volker
V
Messa
Piergiorgio
P
Berloco
Pasquale
P
Montanaro
Domenico
D
Veroux
Pierfrancesco
P
Federico
Stefano
S
Bartezaghi
Marta
M
Corbetta
Giuseppe
G
Ponticelli
Claudio
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D016001:Confidence Intervals; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000097:blood / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D000068338:Everolimus; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology* / Q000401:mortality / Q000502:physiology; D019520:Living Donors; D008875:Middle Aged; D010349:Patient Compliance; D018579:Patient Selection; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D016019:Survival Analysis; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
D007166:Immunosuppressive Agents; D014280:Triglycerides; D016572:Cyclosporine; D000068338:Everolimus; D003404:Creatinine; D020123:Sirolimus