Immunosuppression in liver transplant recipients with renal impairment

Abstract

Renal injury has been recognized as an increasingly prevalent complication of liver transplantation (LT) over the last decade. Both acute and chronic renal injuries occur with high frequency in liver transplant recipients and are associated with increased morbidity and mortality. The risk of immediate post-LT kidney dysfunction is increased in patients with pre-transplant kidney failure, hepato-renal syndrome (HRS), and intra-operative or post-operative hypotension. Thus with the improvement in life expectancy after LT, chronic kidney disease (CKD) has emerged as an increasingly prevalent complication among long-term survivors. Although post-LT renal injury is often multifactorial, one of the dominant mediators is the use of calcineurin inhibitors (CNI), namely Cyclosporine (CsA) and Tacrolimus (Tac), which are the cornerstone of immunosuppression in LT recipients. These drugs indeed intrinsically share a variety of renal toxicities, ranging from oligoanuric acute renal failure to chronic kidney disease. Optimization of immunosuppression for protection of kidney function must, therefore, be considered a major goal after LT, in particular for patients with already impaired renal function. The aim of this article is to review the epidemiology, risk factors, and consequences of post-LT renal dysfunction and to discuss the current approaches to overcome CNI toxicity after LT, both in the early post-operative period and in the long-term, focusing on manipulation of immunosuppressive agents. The issue of combined liver/kidney transplantation in LT candidates with renal failure is beyond the scope of this review and will not be considered herein.