Association between Noninvasive Liver Biomarkers and Graft Outcomes in Kidney Transplant Recipients

Background: Though studies have suggested that metabolic risk profiles may be prognostic factors in kidney transplant recipients (KTRs), the prognostic significance of fatty liver severity, a known surrogate of metabolic risk, in KTRs has not been previously investigated. This study aimed to evaluate the association between non-invasive liver biomarkers and graft outcomes in KTRs. Methods: Patients who underwent deceased or living donor kidney transplantation (KT) between January 2000 and December 2022 were collected. Hepatic fibrosis burdens of KTRs were assessed using the Fibrosis-4 (FIB-4) score and the non-alcoholic fatty liver disease fibrosis score (NFS), one month after KT. The primary outcome was a composite of 50% estimated glomerular filtration rate (eGFR) decline and graft failure. Secondary outcomes included individual outcomes of 50% eGFR decline, graft failure, and acute rejection including both cellular and antibody-mediated rejection. Results: A total of 3,092 patients were grouped into three categories according to FIB-4 scores. During a mean follow-up of 6.0 years, the composite outcome occurred in 519 (2.8/100 person-years) patients. For the secondary outcomes, incidence rates for 50% eGFR decline, acute rejection, and graft failure were 2.3, 2.3, and 1.5 per 100 person-years, respectively. The cumulative incidences of all outcomes were higher in patients with higher FIB-4 scores (all P <0.05; Fig 1). In multivariate Cox models, the highest score group (FIB-4≥2.67) had a 2.05-fold (95% confidence interval [CI], 1.44-2.91; P<0.001) higher risk of the composite outcome compared to the lowest score group (FIB-4<1.30). The highest score group showed higher risk of the secondary outcomes compared to the lowest score group, with risk ratios of 1.75 (95% CI, 1.16-2.66), 1.62 (95% CI, 1.06-2.46), 2.23 (95% CI, 1.43-3.46). Similar findings were observed for NFS. Conclusion: Higher liver fibrosis scores were associated with unfavorable graft outcomes in KTRs.Figure 1. Cumulative incidence of graft outcomes according to FIB-4 score