Work

Gray matter atrophy in the middle frontal gyrus mediates post-traumatic stress symptoms in post-kidney transplant patients: The role of elevated urea levels

Year: 2025

Type: article

Abstract: BACKGROUND: Kidney transplant recipients (KTRs) face numerous stressors including the risk of graft rejection, life-threatening infections, and long-term immunosuppressive therapy, which often contribute to post-traumatic stress symptoms (PTSS) that significantly impair psychological well-being and recovery. While there is evidence linking PTSS to brain gray matter volume (GMV), research on KTR populations remains limited. Additionally, most transplanted kidneys fail to recover completely and cannot function at the level of kidneys in healthy individuals, with evidence indicating consequent neurotoxic effects. However, the relationship between renal function, brain GMV, and PTSS remains poorly understood. METHODS: A cohort of KTRs was assessed for PTSS using the Impact of Event Scale-Revised (IES-R), and 3D-T1 magnetic resonance imaging (MRI) scans were analyzed using voxel-based morphometry to measure GMV. Renal function was also quantified, and regression and mediation analyses were conducted to explore the relationship between renal function, GMV, and PTSS. RESULTS: The analysis revealed significant reductions in GMV in the prefrontal cortex regions of KTRs with higher PTSS scores. Elevated urea levels were correlated with both reduced GMV and increased PTSS severity. Notably, mediation analysis indicated that decreased GMV mediated the relationship between high urea levels and increased PTSS. CONCLUSION: This study provides novel evidence linking elevated urea levels with increased PTSS via decreased GMV in the frontal lobe of KTRs. These findings suggest that GMV changes may serve as biomarkers for PTSS in KTRs, and that urea levels may be a contributing factor to GMV alterations and PTSS.

Source: Journal of Affective Disorders

DOI: 10.1016/j.jad.2025.04.168