Good outcomes with cyclosporine very low exposure with everolimus high exposure in renal transplant patients.
BACKGROUND
The aim of the study was to compare efficacy of cyclosporine (CsA) very low exposure with everolimus high exposure, with respect to CsA standard exposure with enteric-coated mycophenolate sodium (EC-MPS) therapy.


METHODS
In a randomized, prospective, single-center, open-label study, patients were enrolled to receive either everolimus (C0 (trough level) 8-12 ng/mL) + CsA (C2 (CsA level 2 hours after drug administration) 250-300 ng/mL) + steroids, or EC-MPS (1,440 mg/day) + CsA (C2 500-700 ng/mL) + steroids. Fifty-six patients were enrolled in the everolimus group, 50 in the EC-MPS group. Efficacy was evaluated at 3 and 12 months.


RESULTS
Characteristics of groups were similar. Biopsy-proven acute rejection (BPAR) rates were similar in both groups (everolimus 18.8% vs. EC-MPS 18.2%). Everolimus patients had a lower incidence of delayed graft function (DGF) than EC-MPS patients (22.6% vs. 40.9%; p<0.05; relative risk [RR] = 0.65). One-year graft survival was 95% in the everolimus group and 88% in the EC-MPS group (p=NS). CsA dose at 1 year was lower in the everolimus group (1.52 ± 0.67 vs. 2.55 ± 0.79 mg/kg; p<0.0001). Estimated glomerular filtration rate (eGFR; Cockcroft-Gault) was higher in the everolimus group (81.64 ± 32.67 vs. 62.62 ± 22.81 ml/min; p<0.001). Systolic blood pressure was lower in the everolimus group (124.9 ± 14.64 mm Hg vs. 131.1 ± 13.23 mm Hg; p=0.03). Hemoglobin blood levels were slightly lower in the everolimus group (12.62 ± 1.42 vs. 13.01 ± 1.3 g/L; p=NS; for anemia, RR=1.302). Serum cholesterol was similar in both groups (everolimus 219.1 ± 47.20 vs. EC-MPS 207.2 ± 38.8 mg/dL; p=NS), but everolimus patients used more statins (RR=1.49). Twenty-four-hour proteinuria was higher in the everolimus group (519.7 ± 77.31 vs. 296.7 ± 33.42 mg/24 hours; p=0.01).


CONCLUSIONS
Everolimus regimen compared with EC-MPS regimen is associated with lower incidence of DGF, slightly better 1-year graft survival rate, a significantly higher GFR and lower systolic blood pressure.
Renal Unit, Careggi University Hospital, Viale Pieraccini 18, Florence, Italy. elisabettabertoni@gmail.com
Elisabetta
E
Bertoni
Aida
A
Larti
Giuseppina
G
Rosso
Maria
M
Zanazzi
Lorenzo
L
Di Maria
Maurizio
M
Salvadori
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D016009:Chi-Square Distribution; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects; D051799:Delayed Graft Function / Q000209:etiology; D004359:Drug Therapy, Combination; D000068338:Everolimus; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006084:Graft Rejection / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007558:Italy; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D011446:Prospective Studies; D011507:Proteinuria / Q000209:etiology; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013997:Time Factors; D016896:Treatment Outcome
D015415:Biomarkers; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D009173:Mycophenolic Acid; D020123:Sirolimus