RENAL INJURY CONTINUUM IN LIVER TRANSPLANTATION: THE ROLE OF MESENCHYMAL STEM CELLS IN MINIMIZING TACROLIMUS NEPHROTOXICITY

Abstract

Background. Acute kidney injury (AKI) is a common complication occurring in up to 95% of liver transplantations and carrying a 2.96-fold increased risk of mortality and a 3.76-fold higher risk of liver graft failure. Objective. To present the concept of renal injury continuum in liver transplantation and evaluate the effectiveness of mesenchymal stem cells (MSCs) in minimizing tacrolimus nephrotoxicity. Materials and methods. Liver transplant patients were studied using KDIGO criteria for diagnosing acute kidney injury (AKI) and chronic kidney disease (CKD). Results. AKI developed in 39-58% of liver recipients. The main risk factors included initial condition severity (Child-Pugh ≥10 points), intraoperative blood loss (≥1200 ml) and tacrolimus nephrotoxicity (58% of cases). In the long term, 68.2% of patients developed stage 3 CKD, which correlated with high tacrolimus concentrations. There has been detected an association between the degree of renal dysfunction and the risk of immunological complications (up to 40% in CKD stage 3C). The use of MSCs allowed for the reduction of tacrolimus concentration without rejection rate increase, it accelerated renal function recovery, and reduced the incidence of CKD in the long term. The immunomodulatory effect of MSCs was confirmed by a decreased number of effector cells (CD16+56+ NK cells, CD3+CD4+ TEM, CD3+CD8+TEMRA) as well as by reduced anti-HLA antibody levels. Conclusions. Renal injury in liver transplantation represents a continuum of interrelated processes covering all stages of transplantation. The use of MSCs promotes immunological tolerance formation, allowing for safe tacrolimus dosage tapering and nephrotoxicity reduction, thus improving both renal and overall clinical outcomes in liver transplant recipients.