AI Article Synopsis

  • Many kidney transplant patients are classified as having no rejection after biopsy, but some may actually have undetected rejection activities.
  • A study of over 5,000 biopsies found that more than half were marked as no rejection, yet many showed signs of subthreshold T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR).
  • Patients with these hidden rejection activities are at increased risk of future graft issues, as higher levels of TCMR and ABMR correlate with worse kidney function and higher chances of rejection in subsequent biopsies.

Article Abstract

Most kidney transplant patients who undergo biopsies are classified as having no rejection based on consensus thresholds. However, we hypothesized that because these patients have normal adaptive immune systems, T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR) may exist as subthreshold activity in some transplants currently classified as no rejection. To examine this question, we studied genome-wide microarray results from 5086 kidney transplant biopsies (from 4170 patients). An updated molecular archetypal analysis designated 56% of biopsies as no rejection. Subthreshold molecular TCMR and/or ABMR activity molecular activity was detectable as elevated classifier scores in many biopsies classified as no rejection, with ABMR activity in many TCMR biopsies and TCMR activity in many ABMR biopsies. In biopsies classified as no rejection histologically and molecularly, molecular TCMR classifier scores correlated with increases in histologic TCMR features and molecular injury, lower estimated glomerular filtration rate, and higher risk of graft loss, and molecular ABMR activity correlated with increased glomerulitis and donor-specific antibody. No rejection biopsies with high subthreshold TCMR or ABMR activity had a higher probability of having TCMR or ABMR, respectively, diagnosed in a future biopsy. We conclude that many kidney transplant recipients have unrecognized subthreshold TCMR or ABMR activity, with significant implications for future problems.

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http://dx.doi.org/10.1016/j.ajt.2024.07.034DOI Listing

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