Impact of Subclinical Borderline Inflammation on Kidney Transplant Outcomes

Michael E Seifert, Gaurav Agarwal, Miriam Bernard, Ellen Kasik, S Sikandar Raza, Huma Fatima, Robert S Gaston, Vera Hauptfeld-Dolejsek, Bruce A Julian, Clifton E Kew, Vineeta Kumar, Shikha Mehta, Song Ong, Frida Rosenblum, Graham Towns, Roslyn B Mannon

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Background: Surveillance biopsies permit early detection of subclinical inflammation before clinical dysfunction, but the impact of detecting early subclinical phenotypes remains unclear.

Methods: We conducted a single-center retrospective cohort study of 441 consecutive kidney transplant recipients between 2015 and 2018 with surveillance biopsies at 6 months post-transplant. We tested the hypothesis that early subclinical inflammation (subclinical borderline changes, T cell-mediated rejection, or microvascular injury) is associated with increased incidence of a composite endpoint including acute rejection and allograft failure.

Results: Using contemporaneous Banff criteria, we detected subclinical inflammation in 31%, with the majority (75%) having a subclinical borderline phenotype (at least minimal inflammation with mild tubulitis [>i0t1]). Overall, subclinical inflammation was independently associated with the composite endpoint (adjusted hazard ratio, 2.88; 1.11-7.51; P = 0.03). The subgroup with subclinical borderline inflammation, predominantly those meeting the Banff 2019 i1t1 threshold, was independently associated with 5-fold increased hazard for the composite endpoint (P = 0.02). Those with concurrent subclinical inflammation and subclinical chronic allograft injury had worse outcomes. The effect of treating subclinical inflammation was difficult to ascertain in small heterogeneous subgroups.

Conclusions: Subclinical acute and chronic inflammation are common at 6 months post-transplant in kidney recipients with stable allograft function. The subclinical borderline phenotype with both tubulitis and interstitial inflammation was independently associated with poor long-term outcomes. Further studies are needed to elucidate the role of surveillance biopsies for management of allograft inflammation in kidney transplantation.

Original languageEnglish (US)
Pages (from-to)e663
JournalTransplantation Direct
Issue number2
StatePublished - Feb 2021


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