Metabolomic and Proteomic Analysis of Renal Function After Liver Transplantation

Xiaoling Wang^1*Nadja Grobe¹Barbara Franchin²Josh Levitsky³Paolo Cravedi²Peter Kotanko^1,2

• ¹Renal Research Institute, New York, United States
• ²Icahn School of Medicine at Mount Sinai, New York, New York, United States
• ³Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States

AbstractBackground: Renal dysfunction is a common and serious complication in patients with end-stage liver diseases. While some patients recover renal function after liver transplantation (LT), others do not. Additionally, patients with normal kidney function (Normal-KF) before LT may develop post-transplant renal dysfunction. Early identification of patients at risk for impaired kidney function (Impaired-KF) post-LT is critical to improving outcomes. This study integrated metabolomic and proteomic analyses to investigate molecular profiles distinguishing Normal-KF from Impaired-KF post-LT. Methods: Nine LT recipients were classified into Normal-KF (n=5) and Impaired-KF (n=4) groups. One additional recipient with pre-transplant renal function impairment who recovered renal function after LT, was analyzed separately. Plasma samples were collected at 2- and 5-weeks post-LT. The metabolomic and proteomic profiles were assessed by untargeted liquid chromatography-tandem mass spectrometry.Results: Metabolomic analysis identified 29 significantly altered metabolites between Normal-KF and Impaired-KF (fold change>2, p<0.05). Proteomic analysis revealed 45 differentially expressed proteins (fold change>1.25, p<0.05). For the recovered patient, the metabolomic profile closely resembled Normal-KF, whereas the proteomic profile remained aligned with Impaired-KF at both 14- and 35-days post-LT. From week 2 to week 5, both the metabolomic and proteomic profiles of the recovered patient showed trends toward the Normal-KF. Conclusion: This study revealed distinct metabolomic and proteomic signatures associated with renal dysfunction post-LT. Proteomic profiles indicated a delayed recovery compared to metabolomic profiles, suggesting a dynamic and muti-layered renal recovery process. Further research is warranted to elucidate the functional implications of the differential proteins and metabolites for improved monitoring and therapeutic strategies.