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Wound Healing Complications in Kidney Transplant Recipients Receiving Everolimus

Ueno, Priscilla MS; Felipe, Claudia PharmD; Ferreira, Alexandra MD; Cristelli, Marina MD; Viana, Laila MD; Mansur, Juliana MD; Basso, Geovana MD; Hannun, Pedro MS; Aguiar, Wilson MD; Tedesco Silva, Helio Jr MD; Medina-Pestana, Jose MD

doi: 10.1097/TP.0000000000001392
Original Clinical Science-General

Background: De novo use of mammalian target of rapamycin inhibitors after kidney transplantation is associated with a concentration-dependent incidence of wound healing adverse events (WHAE). The objective of this analysis was to compare the incidence of WHAE in patients receiving everolimus (EVR) or mycophenolate sodium (MPS).

Methods: This was a predefined subanalysis of a single-center prospective randomized study in which 288 kidney transplant recipients receiving tacrolimus and prednisone were randomized for 3 different regimens: rabbit antithymocyte globulin (r-ATG)/EVR (N = 85); basiliximab (BAS)/EVR (N = 102); BAS/MPS (N = 101). Clinical WHAE were prospectively collected using a prespecified case report form in all study visits. Abdominal ultrasound was performed at 30 days posttransplant to capture subclinical abnormalities. Surgeons were blinded to randomized treatment and no specific surgical procedures were implemented.

Results: A higher proportion of patients in BAS/EVR showed at least 1 clinical WHAE (22.3% vs 35.3% vs 22.0%, P = 0.03) and total clinical and subclinical WHAE (35% vs 42% vs 26%, P = 0.014) compared with BAS/MPS, respectively. A higher proportion of patients in r-ATG/EVR showed subclinical WHAE (13% vs 7% vs 4%, P = 0.025) compared with BAS/MPS, respectively. Patients receiving EVR showed a higher risk of developing clinical or subclinical WHAE (r-ATG/EVR vs BAS/MPS hazard ratio 1.30; BAS/EVR vs BAS/MPS hazard ratio 1.73, P = 0.028).

Conclusions: In this cohort of de novo kidney transplant recipients receiving tacrolimus and prednisone, the use of EVR was associated with higher incidence of combined clinical and subclinical WHAE compared with MPS.

In a single-center prospective randomized study, 288 de novo kidney transplant recipients receiving everolimus, tacrolimus and prednisone show higher incidence of combined clinical and subclinical wound healing adverse events compared to mycophenolate sodium.

1 Nephrology Division, Hospital do Rim, Universidade Federal de Sao Paulo, São Paulo, SP, Brazil.

2 Urology Division, Hospital do Rim, Universidade Federal de Sao Paulo, São Paulo, SP, Brazil.

Received 2 February 2016. Revision received 24 May 2016.

Accepted 9 June 2016.

Clinical Trial Notation: Efficacy and Safety of Induction Strategies Combined With Low Tacrolimus Exposure in Kidney Transplant Recipients Receiving Everolimus or Sodium Mycophenolate. Number NCT01354301.

The following authors of this manuscript have conflicts of interest to disclose: H.T.-S. has received speaker's fees travel or accommodation expenses for development of educational presentations scientific advice from Novartis, Pfizer Roche. Jose Medina-Pestana has received speaker's fees travel or accommodation expenses for development of educational presentations scientific advice from Bristol- Myers Squibb, Novartis, Pfizer Roche. Claudia Felipe has received speaker's fees for development of educational presentations travel or accommodation expenses from Novartis Pfizer. Marina Cristelli has received speaker's fees for development of educational presentations travel or accommodation expenses from Novartis Pfizer. The institution, Hospital do Rim, has received Research Grants for clinical studies from Novartis, Pfizer, Astellas, Bristol-Myers Squibb, Roche LifeCycle Pharma.

P.U., C.F., H.T.-S., J.M.-P. participated in research design. P.U., C.F., A.F., M.C., L.V., J.M., G.B., P.H., W.A., H.T.-S., J.M.-P. participated in the writing of the article. P.U. C.F., A.F., M.C., L.V., J.M., G.B., P.H., H.T.-S., J.M.-P. participated in the performance of the research. P.U., C.F., H.T.-S., J.M.-P. participated in data analysis.

Correspondence: Helio Tedesco-Silva Jr, MD, Nephrology Division, Hospital do Rim, Universidade Federal de São Paulo, Rua Borges Lagoa, 960-11° Andar, Zip code: 04038-002, São Paulo, Brazil. (heliotedesco@medfarm.com.br).

Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.transplantjournal.com).

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