Late Conversion to Everolimus with Calcineurin Inhibitor Minimization in Stable Kidney Transplant Recipients - Analysis of Factors Affecting ΔeGFR

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Abstract

Background

Immunosuppressive regimens that minimize exposure to calcineurin inhibitors (CNIs) following kidney transplantation have been widely investigated in order to reduce the burden of CNI-related complications. Recent trials have focused on the use of everolimus to facilitate CNI withdrawal or minimization. Previous studies had shown that late conversion to everolimus had no overall renal benefit. However, late conversion of kidney transplant recipients to everolimus has demonstrated renal improvement in patients with a baseline estimated glomerular filtration rate (eGFR) of above 50 ml/min/1.73m2 or in patients who remained on everolimus medication. The aim of this study is to analyze the factors affecting graft function after late conversion to everolimus with CNI minimization in kidney transplant recipients.

Patients and Methods

A 1-year retrospective pilot study of 56 kidney recipients converted from antimetabolites with standard exposure CNIs to everolimus with CNI minimization was performed. The recipients enrolled in this study had normal or slightly impaired renal function defined as a serum creatinine (S-Cr) value<2.0 mg/dl, and normal or slightly increased albuminuria defined as a urinary albumin excretion rate <100 mg/g Cr. For the assessment of graft function, we used ΔeGFR according to the formula ΔeGFR=(eGFR at 12 months after conversion)-(eGFR at conversion). We evaluated the relationship betweenΔeGFR and clinical parameters in kidney transplant recipients enrolled in this study.

Results

The average time from transplant to conversion was 42.9±44.1 months, and treatment with everolimus was stopped due to adverse events in 17 patients (30.3%). ΔeGFR was significantly higher in patients who remained on everolimus than in those who discontinued everolimus medication. Univariate linear regression analysis revealed that ΔeGFR correlated negatively with urinary albumin excretion (R=0.479, p=0.000216) and kidney age (donor age at transplantation+time from transplantation to conversion)(R=0.275, p=0.048). Multivariate linear regression analysis indicated that urinary albumin excretion and everolimus continuation were independently associated with ΔeGFR.

Conclusion

Our results suggested that late conversion of kidney transplant recipients to everolimus with CNI minimization may lead to improvement in graft function compared to standard CNI therapy, if they remained on everolimus treatment. Urinary albumin excretion may be a marker of generalized endothelial or vascular damage, and graft function in patients with renal or systemic endothelial damage may deteriorate due to late conversion to everolimus with CNI minimization.

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