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24-month monitoring to a late conversion from a Calcineurin inhibitor regime to everolimus in kidney transplant recipients

Montero, Camilo | 2015-11-10

Introduction: Graft survival has remained stable in the long term, without significant increase in recent years. Among the main causes of renal graft loss after the first year are death with functioning kidney graft from cardiovascular, infectious and neoplastic causes, and chronic graft injury for immunological and non-immunological causes. This has been attributed to the chronic use of calcineurin inhibitors (CNI), increased cardiovascular risk, the incidence of certain infections and increased incidence of post-transplant malignancies. Also, reports show the increased frequency of histological lesions related to nephrotoxicity caused by these drugs. The switch from CNI to mTOR inhibitors may decrease some of these effects in the long term. We conducted a retrospective study of conversion to mTOR inhibitors in patients with a CNI-based scheme. Materials and methods: A retrospective single-center case study was conducted, including renal transplantation patients with more than 6 months of transplantation, who were switched to everolimus, after an abrupt withdrawal of calcineurin inhibitor with a previous biopsy of the renal graft. Patients with evidence in the biopsy of changes of acute rejection, glomerular disease or relapse of acute tubular necrosis were excluded. Similarly, patients with proteinuria over 1 g in 24 hours and patients with clinical acute rejection within 3 months prior to conversion were excluded. A total of 40 patients were included, monitoring of variables such as glomerular filtration rate, proteinuria, lipids, use of antihypertensive drugs and adverse effects was performed after conversion until Day 720.Results: The results, after 720 days of monitoring, show an increased glomerular filtration rate in 65% of the patients and a decrease in 30% of them. The proteinuria increased with respect to the pre-conversion values in all the patients, however proteinuria >1 g was present in 6 of the 40 patients after the same monitoring time. Of the 6 patients with proteinuria, 5 patients had more than 5 years of transplantation and moderate to severe interstitial fibrosis in the pre-conversion biopsy, which would be linked to the increase in proteinuria. The incidence of post-conversion acute rejection was 5%. The conversion tolerance was adequate, with a low frequency of adverse events that could lead to discontinuance of therapy. Conclusion: Late conversion to everolimus in patients with kidney transplant from a CNI-based scheme is safe, improves renal function without a significant increase in the degree of proteinuria, associated with pre-conversion biopsies evidencing no significant degrees of interstitial chronicity. The tolerance to the scheme is appropriate and the frequency of acute rejection was not significantly increased.