- Design
- Multicentre observational cohort
- Population
- 5,762 adult kidney transplant recipients, 790 with early TCMR
- Primary outcome
- Death-censored graft loss
- Effect
- TCMR HR 2.84 (2.38–3.3); persistent vs responsive HR 3.21 (2.19–4.71)
This observational cohort, published in July, included all adult kidney transplant recipients from 2013 to 2019 at six centres in the United States and Europe: 5,762 patients and 9,780 biopsies.
T cell-mediated rejection occurred in 790 (13.6%) in the first year. Despite treatment, 32% still had rejection on follow-up biopsy and 36% deteriorated clinically. Clinical and histological response often disagreed: only half of those who improved clinically were free of rejection on biopsy, and over a third of those who worsened had none. Rejection was associated with nearly three times the risk of death-censored graft loss (HR 2.84, 95% CI 2.38–3.3), and persistent rejection with three times the risk of responsive rejection (HR 3.21, 2.19–4.71), independent of clinical response. Graft loss rose stepwise with persisting tubulointerstitial inflammation.
Early cellular rejection is often treated as a minor, easily reversed event. These data suggest it frequently resists treatment and that clinical response is a poor guide. The study is observational, but it supports biopsy-guided follow-up after treatment.
- Consider a follow-up biopsy after treating early T cell-mediated rejection rather than relying on clinical response.
- Treat persistent tubulointerstitial inflammation on biopsy as a high-risk finding needing escalation.
- Review immunosuppression levels and adherence at every rejection episode.
- Discuss the long-term significance of early rejection openly with recipients.
Why it matters
This challenges the assumption that early cellular rejection is benign once treated.
Don't overread it
This was observational; it does not show that biopsy-guided treatment improves graft survival.
The statistics, in plain English
An HR of 3.21 means persistent rejection carried about three times the graft loss of rejection that responded. The interval 2.19–4.71 is well clear of 1.0, and landmark analyses supported it.
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