Unifying Concepts

Diagnostic Criteria of Acute Rejection in Kidney Transplants

The gold standard for diagnosing acute rejection in kidney transplant recipients is tissue biopsy. Indications to pursue graft biopsy over concern for acute rejection include either an acute, otherwise unexplained deterioration in graft function or the presence of a biomarker consistent with acute rejection.

Histologic criteria for diagnosing acute allograft rejection

Acute T cell–mediated rejection (TCR)

  • Ia: >25% Interstitial inflammation with moderate tubulitis (t2)
  • Ib: >25% Interstitial inflammation with severe tubulitis (t3)
  • IIa: Mild-to-moderate intimal arteritis (v1)
  • IIb: Severe intimal arteritis (v2)
  • III: Transmural arteritis and/or fibrinoid necrosis

Acute antibody-mediated rejection (AMR): all three criteria below required

  • Histologic evidence of tissue injury including one or more of the following:
    • Microvascular inflammation (g>0 and/or ptc>0)
    • Arteritis (v>0)
    • Thrombotic microangiopathy
    • Acute tubular injury
  • Evidence of current/recent antibody interaction with endothelium including one or more of the following:
    • Positive C4d staining of peritubular capillaries
    • Moderate microvascular inflammation (g+ptc ≥2)
    • Increased expression of gene transcripts in biopsy tissue strongly associated with AMR
  • Serologic evidence of donor-specific antibodies (DSA)
    • Positive C4d staining or presence of AMR-associated gene transcripts may substitute for DSA



  1. Cooper JE. Evaluation and Treatment of Acute Rejection in Kidney Allografts. Clin J Am Soc Nephrol. 2020 Mar 6;15(3):430-438. [Medline]
  2. Singh N, Samant H, Hawxby A, Samaniego MD. Biomarkers of rejection in kidney transplantation. Curr Opin Organ Transplant. 2019 Feb;24(1):103-110. [Medline]


Created Mar 17, 2022.

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