A low-grade systemic inflammatory environment early after kidney transplantation is associated with long-term kidney graft loss, a new study finds.
Investigations examined the associations between 21 inflammatory biomarkers measured in serum at 10 weeks after transplantation and protocol or indicated biopsy findings at 6 weeks and 1 year in 699 kidney transplant recipients. Overall, 12.2% of patients experienced death-censored graft loss due to rejection while on immunosuppression (67.9%), recurrence of the primary kidney disease (15.5%), de novo glomerulonephritis (4.8%), and other causes (11.9%).
An overall inflammation score based on 11 biomarkers was significantly associated with long-term death-censored kidney graft loss both as a continuous and categorical variable, Torbjørn F. Heldal, MD, PhD, of Telemark Hospital Trust in Skien, Norway, and colleagues reported in Frontiers in Immunology. The top quartile of the overall inflammation score was significantly associated with a 3.2-fold increased risk for graft loss compared with the bottom quartile. Adding biopsy findings of inflammation and interstitial fibrosis and tubular atrophy (IFTA) to the overall inflammation score strengthened the associations with graft loss. The results held even after adjustment for de novo/pre-existing donor-specific antibodies and delayed graft function.
The investigators also examined 5 pathway-specific inflammation scores. The top vs bottom quartile of the vascular/general inflammation score was significantly associated with biopsy findings and a 2.8-fold increased risk of graft loss. Among the vascular biomarkers, sTNFR1, which reflects activity of the tumor necrosis factor system, stood out. The top quartile of fibrogenesis activity also was significantly associated with a 2.1-fold increased risk of graft loss. Of these biomarkers, GDF-15 and osteopontin were the most consequential.
“Our findings describe strong associations between subclinical low-grade systemic inflammation in the early phase after transplantation and death-censored graft loss, especially for markers reflecting fibrogenesis activity and vascular inflammation,” Dr Heldal’s team wrote.
Heldal TF, Åsberg A, Ueland T, et al. Systemic inflammation early after kidney transplantation is associated with long-term graft loss: a cohort study. Front Immunol. 2023;2;14:1253991. doi:10.3389/fimmu.2023.1253991