Renal protection strategies after heart transplantation

Abstract

Renal dysfunction caused by calcineurin inhibitor (CNI) nephrotoxicity occurs often and contributes significantly to late mortality after heart transplantation (HTx). Over the last decades, this has prompted many clinical studies in an effort to develop kidney-protecting immunosuppressive strategies including delayed CNI start, minimization, withdrawal, or even de novo CNI avoidance. In the past, these strategies often failed due to the lack of efficacy. Since 2009, novel CNI-reducing strategies have been under investigation. These strategies minimize renal damage using induction agents such as antithymocyte globulin and alternative immunosuppressive agents such as the mechanistic target of rapamycin inhibitors (sirolimus or everolimus) or mycophenolate.This review outlines the recent results of using these renal protection strategies including their drawbacks. We also discuss alternative approaches to optimize individual immunosuppressive therapies after HTx. K E Y W O R D Scalcineurin inhibitors, heart transplantation, immunosuppression, mechanistic target of rapamycin inhibitors, nephrotoxicity, renal protecting strategies

Imaging techniques to study drug transporter function in vivo

“…Moreover, radiolabeled drugs may find use in evaluating protective pharmacologic strategies to mitigate organ toxicities of certain drugs (e.g. nephrotoxicity) (Manohar & Leung, 2017;Reichart et al, 2017).…”

Comparing everolimus-based immunosuppression with reduction or withdrawal of calcineurin inhibitor reduction from 6 months after heart transplantation: The randomized MANDELA study

“…Heart transplant patients frequently have chronic renal failure prior to transplant, rendering them vulnerable to nephrotoxic insults such as calcineurin inhibitor (CNI)-related nephrotoxicity, and are at high risk for progression to end-stage renal disease with an associated reduction in survival. 1,2 The mammalian target of rapamycin (mTOR) inhibitor everolimus acts synergistically to CNI agents, 3 prompting an extensive program of research into how it can best be used to reduce or even avoid the need for CNI therapy 4 and thus alleviate CNI-related toxicity.…”

The Enigma of Heart-kidney Transplantation

“…Without doubt, calcineurin inhibitors (CNIs) are the most important contributors to end-stage renal disease in the long term, which has an incidence of up to 20% of HTx survivors within 10 y. 2 Therefore, the arising enigma in heart-kidney transplantation (HKT) is to identify pre-HTx patients with predominantly hemodynamically mediated renal failure, which may resolve spontaneously (or not) after successful HTx.…”

“…3 In the early and midterm follow-up period, post-HTx CNI minimization or even CNI-withdrawal immunosuppressive regimens based on the mammalian target of rapamycin inhibitor everolimus should be applied to protect renal function as successfully shown in randomized controlled trials. 2,4 Notably, it should be kept in mind that CNI-free patients have a higher risk of biopsy-proven acute cellular rejection, which is mainly of low histological grade and without hemodynamic compromise.…”

“…Without doubt, calcineurin inhibitors (CNIs) are the most important contributors to end-stage renal disease in the long term, which has an incidence of up to 20% of HTx survivors within 10 y. 2…”