Subclinical Inflammation Increases Long-Term Rejection and Graft Loss

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Markers of subclinical inflammation detected on surveillance kidney allograft biopsies are associated with elevated long-term risk of rejection and graft loss, reports a pre-proof paper in Kidney International.

From a cohort of 1000 sequential kidney transplant recipients at the authors’ center from 2013 to 2017, the analysis included 586 patients who underwent surveillance biopsy in the first year after transplantation and did not experience clinical rejection. Of these, 304 patients were found to have subclinical inflammation with tubulitis (SCI-T). This group was further classified as having subclinical borderline changes (182 patients) or subclinical T-cell-mediated rejection (122 patients; based on a Banff 2019 classification of 1A or higher.).

Over a median follow-up of 5 years, clinical and immunologic events were analyzed in terms of the presence and type of subclinical inflammation. The primary outcomes were clinical biopsy-proven acute rejection (C-BPAR) after the index biopsy and death-censored graft loss.

Episodes of C-BPAR were observed at a median follow-up of 2 years. This outcome was significantly more frequent in the combined SCI-T group compared with patients with no subclinical inflammation (17% vs. 4.6%; adjusted odds ratio [OR], 3.8). Patients with SCI-T were also at higher risk for death-censored graft loss (OR, 1.99). Alloimmune injury was more likely to be the cause of graft loss in the SCI-T group (67% vs. 50%).

Previous studies have suggested that low-level inflammation early after transplantation may be associated with an increased risk of adverse outcomes. However, there are few data on how subclinical inflammation on surveillance biopsies affects long-term allograft survival.

This 5-year follow-up study shows increased risks of C-BPAR and death-censored graft loss in kidney transplant recipients. Early surveillance biopsies may identify patients at higher risk for poor long-term outcomes, potentially enabling more personalized approaches to immunosuppression. The researchers note, “[T]he prognosis of SCI-T in general is good if not followed by subsequent clinical rejection” [Mehta RB, et al. Long-term immunological outcomes of early subclinical inflammation on surveillance kidney allograft biopsies. Kidney Int, published online ahead of print August 29, 2022. doi: 10.1016/j.kint.2022.07.030;].