Multi-Omics Identification of Acute Phase Drivers of Kidney Injury After Liver Transplantation

The highest incidences of kidney injury and chronic renal failure that occur after liver transplantation. More than 50% of patients get affected by chronic kidney diseases within 5 years of liver transplantation adding to the burden of kidney transplantation, for which more than 80,000 people are already waiting for a donor. Early identification and management of kidney injury after liver transplantation can increase the success rate and long-term survival of the patients. Therefore, we planned a detailed multi-omics study to understand the mechanisms behind the liver-kidney crosstalk and identify the early markers or drivers. In this study we performed orthotopic liver transplantation (OLT) using inbred male C57BL/6 mice. Blood, urine, kidney tissue and liver graft samples were collected at 24 hours after the transplantation. Liver chemistry and kidney injury markers were measured and lipidomics, transcriptomics, proteomics and metabolomics of liver and kidney tissue were analyzed in OLT and sham groups, and integrated multi-omics analyses were performed. The plasma levels of ALT, AST and ALP were significantly higher in the OLT group as compared to the sham group. There was a higher trend of plasma creatine and BUN/creatinine ratio in the OLT group. Multi-omics analysis revealed several common markers elevated in both OLT liver and kidney as compared to the sham. The lipidomics proteomics, transcriptomics and metabolomics profiles were all significantly affected in the kidney 24 hours after OLT. Many of these markers are related to inflammation, recovery and homeostasis. Acute inflammatory response proteins and complement & coagulation cascade were commonly found to be activated in both liver and kidney after OLT. Kidney inflammatory lipid mediator PGF2a was positively, while pro-resolving RvE1 was negatively associated with plasma ALT. Several of these common drivers including Slc4a1, Bpgm, Lgals3, Srxn1, have human orthologues which can give future direction to early identification and management of kidney injury after liver transplantation. Our study demonstrates that kidney injury begins as early as 24 hours after liver transplantation in mice. Multi-omics analysis revealed coordinated changes in liver and kidney. The results were promising and provided a foundation for understanding the mechanisms driving kidney injury after liver transplantation and for developing future screening and therapeutic strategies. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.