Metabolic Syndrome, Nonalcoholic Fatty Liver Disease, and Graft Inflammation: An Unaddressed Pathogenic Link after Kidney Transplantation.

Kidney transplantation (KT) is the treatment of choice for chronic kidney disease patients, but there is a continued loss of grafts in the long-term (50% at 10 years) due to either patient death or chronic allograft dysfunction. Metabolic syndrome (MS) is very prevalent after KT (30-40%) and its components contribute to the appearance of nonalcoholic fatty liver disease/metabolic dysfunction-associated fatty liver disease (NAFLD/MAFLD) and nonalcoholic steatohepatitis (NASH), which represent the hepatic component of MS. Furthermore, about 20-40% of KT recipients present early graft inflammation, including subclinical inflammation. Thus, the relationship between NAFLD-MAFLD/NASH and graft inflammation may be bidirectional, though no definite link between NAFLD-NASH and graft inflammation is currently known. Additionally, MS-related risk factors are associated with modern immunosuppressants and a negative synergistic effect on graft and patient survival seems plausible. Indeed, proinflammatory cytokines and adipokines released by adipose tissue can generate a low-grade inflammatory state and endothelial dysfunction, both involved in the appearance of CVD, and these disorders are associated with worsening liver lesions and subclinical and clinical atheromatosis. In this review, we discuss the recent clinical evidence regarding the prevalence and risk factors of MS and NAFLD/MAFLD following KT. Additionally, we propose the potential linking mechanism between NAFLD/MAFLD-NASH and post-KT graft inflammation, as well as alternative therapies for NAFLD after KT. Prevention of long-term life-threatening complications in this particular population rests upon better understanding and management of these severe clinical complications.