Prospective randomized study comparing everolimus and mycophenolate sodium in de novo kidney transplant recipients from expanded criteria deceased donor
Alexandra Nicolau Ferreira
Nephrology Division, Hospital do Rim, Universidade Federal de São Paulo, São Paulo, Brazil
Search for more papers by this authorClaudia Rosso Felipe
Nephrology Division, Hospital do Rim, Universidade Federal de São Paulo, São Paulo, Brazil
Search for more papers by this authorMarina Cristelli
Nephrology Division, Hospital do Rim, Universidade Federal de São Paulo, São Paulo, Brazil
Search for more papers by this authorLaila Viana
Nephrology Division, Hospital do Rim, Universidade Federal de São Paulo, São Paulo, Brazil
Search for more papers by this authorJuliana Mansur
Nephrology Division, Hospital do Rim, Universidade Federal de São Paulo, São Paulo, Brazil
Search for more papers by this authorMayara de Paula
Nephrology Division, Hospital do Rim, Universidade Federal de São Paulo, São Paulo, Brazil
Search for more papers by this authorDaniel Wagner
Infectious Diseases Division, Hospital do Rim, Universidade Federal de São Paulo, São Paulo, Brazil
Search for more papers by this authorRenato de Marco
Immunogenetics, Instituto de Imunogenética – AFIP, São Paulo, Brazil
Search for more papers by this authorMaria Gerbase-DeLima
Immunogenetics, Instituto de Imunogenética – AFIP, São Paulo, Brazil
Search for more papers by this authorHenrique Proença
Pathology Division, Hospital do Rim, Universidade Federal de São Paulo, São Paulo, Brazil
Search for more papers by this authorWilson Aguiar
Urology Division, Hospital do Rim, Universidade Federal de São Paulo, São Paulo, Brazil
Search for more papers by this authorJose Medina-Pestana
Nephrology Division, Hospital do Rim, Universidade Federal de São Paulo, São Paulo, Brazil
Search for more papers by this authorCorresponding Author
Helio Tedesco-Silva Junior
Nephrology Division, Hospital do Rim, Universidade Federal de São Paulo, São Paulo, Brazil
Correspondence
Helio Tedesco Silva Junior, Rua Borges Lagoa, 960- 11ª andar, CEP 04038-002 São Paulo Brazil.
Tel.: 55-11-50878113;
fax: 55-11-50878145;
e-mail: [email protected]
Search for more papers by this authorAlexandra Nicolau Ferreira
Nephrology Division, Hospital do Rim, Universidade Federal de São Paulo, São Paulo, Brazil
Search for more papers by this authorClaudia Rosso Felipe
Nephrology Division, Hospital do Rim, Universidade Federal de São Paulo, São Paulo, Brazil
Search for more papers by this authorMarina Cristelli
Nephrology Division, Hospital do Rim, Universidade Federal de São Paulo, São Paulo, Brazil
Search for more papers by this authorLaila Viana
Nephrology Division, Hospital do Rim, Universidade Federal de São Paulo, São Paulo, Brazil
Search for more papers by this authorJuliana Mansur
Nephrology Division, Hospital do Rim, Universidade Federal de São Paulo, São Paulo, Brazil
Search for more papers by this authorMayara de Paula
Nephrology Division, Hospital do Rim, Universidade Federal de São Paulo, São Paulo, Brazil
Search for more papers by this authorDaniel Wagner
Infectious Diseases Division, Hospital do Rim, Universidade Federal de São Paulo, São Paulo, Brazil
Search for more papers by this authorRenato de Marco
Immunogenetics, Instituto de Imunogenética – AFIP, São Paulo, Brazil
Search for more papers by this authorMaria Gerbase-DeLima
Immunogenetics, Instituto de Imunogenética – AFIP, São Paulo, Brazil
Search for more papers by this authorHenrique Proença
Pathology Division, Hospital do Rim, Universidade Federal de São Paulo, São Paulo, Brazil
Search for more papers by this authorWilson Aguiar
Urology Division, Hospital do Rim, Universidade Federal de São Paulo, São Paulo, Brazil
Search for more papers by this authorJose Medina-Pestana
Nephrology Division, Hospital do Rim, Universidade Federal de São Paulo, São Paulo, Brazil
Search for more papers by this authorCorresponding Author
Helio Tedesco-Silva Junior
Nephrology Division, Hospital do Rim, Universidade Federal de São Paulo, São Paulo, Brazil
Correspondence
Helio Tedesco Silva Junior, Rua Borges Lagoa, 960- 11ª andar, CEP 04038-002 São Paulo Brazil.
Tel.: 55-11-50878113;
fax: 55-11-50878145;
e-mail: [email protected]
Search for more papers by this authorSummary
The optimal immunosuppressive regimen for recipients of expanded criteria donor (ECD) kidneys has not been identified. In this single-center study, 171 recipients of ECD kidney transplants were randomized to receive antithymocyte globulin induction, and delayed introduction of reduced dose tacrolimus, prednisone and everolimus (r-ATG/EVR, n = 88), or mycophenolate (r-ATG/MPS, n = 83). No cytomegalovirus (CMV) pharmacological prophylaxis was used. The primary endpoint was the incidence of CMV infection/disease at 12 months. Secondary endpoints included treatment failure [first biopsy-proven acute rejection (BPAR), graft loss, or death] and safety. Patients treated with EVR showed a 89% risk reduction (13.6 vs. 71.6%; HR 0.11, 95% CI 0.06–0.220, P < 0.001) in the incidence of first CMV infection/disease. Incidences of BPAR (16% vs. 5%, P = 0.021), graft loss (11% vs. 1%, P = 0.008), death (10% vs. 1%, P = 0.013), and treatment discontinuation (40% vs. 28%, P = 0.12) were higher in the r-ATG/EVR, leading to premature study termination. Mean glomerular filtration rate was lower in r-ATG/EVR (31.8 ± 18.8 vs. 42.6 ± 14.9, P < 0.001). In recipients of ECD kidney transplants receiving no CMV pharmacological prophylaxis, the use of everolimus was associated with higher treatment failure compared with mycophenolate despite the significant reduction in the incidence of CMV infection/disease (ClinicalTrials.gov.NCT01895049).
Conflict of interest
The institution “Hospital do Rim” received research grants from Novartis and Sanofi to conduct this study.
Alexandra Nicolau Ferreira, Claudia Rosso Felipe, Marina Cristelli, Laila Viana, Juliana Mansur, Mayara de Paula, Daniel Wagner, Renato de Marco, Maria Gerbase-DeLima, Henrique Proença, Wilson Aguiar, and Jose Medina-Pestana have no conflict of interest. Helio Tedesco-Silva received research grants from Novartis and Sanofi.
Supporting Information
| Filename | Description |
|---|---|
| tri13478-sup-0001-FigS1.pptxapplication/mspowerpoint, 67.7 KB | Figure S1. Proportion of patients receiving kidneys with increasing KDPI percentage range in each group. |
| tri13478-sup-0002-FigS2.pptxapplication/mspowerpoint, 80.3 KB | Figure S2. Proportion of patients with 1–4 doses of 1.5 mg/kg of r-ATG in each group. |
| tri13478-sup-0003-FigS3.pptxapplication/mspowerpoint, 96.3 KB | Figure S3. Box-plot distribution of MPA plasma concentrations in each visit during the first year after transplantation (n = number of determinations in each visit). |
| tri13478-sup-0004-FigS4.pptxapplication/mspowerpoint, 131.6 KB | Figure S4. Kaplan Meier estimates and 95% confidence intervals for overall graft survival (A), death-censored graft survival (B) and patient survival (C). Differences between the two groups were identified using the Log-rank test. |
| tri13478-sup-0005-TableS1.docxWord document, 21.3 KB | Table S1. Proportion of patients with EVR and TAC whole blood trough concentrations below the lower limit of therapeutic range in each study visit. |
| tri13478-sup-0006-TableS2.docxWord document, 26.5 KB | Table S2. Individual data of patients with graft loss or death. |
| tri13478-sup-0007-TableS3.docWord document, 52.5 KB | Table S3. Renal function parameters during the first 12 months. |
| tri13478-sup-0008-TableS4.docxWord document, 21.9 KB | Table S4. Timing and drug concentrations of patients with first treated acute rejection episodes. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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