CHAPTER 90: Pediatric Kidney Transplant Rejection

OVERVIEW

• Definition: A recipient’s immune response to foreign antigens expressed by the donor that if unresolved will lead to graft loss

• Incidence:

  • According to Organ Procurement Transplant Network (OPTN) and Scientific Registry of Transplant Recipients (SRTR), in the 2016–2017 cohort, incidence of acute rejection within 1 year was 11.4% overall.¹

  • According to the North American Pediatric Renal Transplant Cooperative Study (NAPRTICS), in the 2012–2017 cohort, probability rate of first acute rejection within 1 year was 12.7% for living donors and 13.2% for deceased donors.²

• Significance:

  • According to NAPRTICS, chronic rejection and acute rejection are the leading causes of graft failure in children.² Therefore prevention as well as early diagnosis and treatment are important in improving long-term outcomes.³

    • From 2008 to 2017, 21.3% and 16.4% of index graft failures were secondary to chronic and acute rejection, respectively.²

TYPES OF REJECTION

• Hyperacute rejection: Occurs within minutes to hours of transplantation when preformed antibodies (HLA or non-HLA) in sensitized patients cause vascular injury via antibody-dependent cytotoxicity.⁴

• Acute rejection (AR): Usually occurs within months, sometimes days or years, of transplantation.⁴ Can be antibody mediated, T-cell mediated, or mixed.

  • Antibody-mediated rejection (AMR): Caused by recipient antibodies against donor-specific molecules (HLA or non-HLA).⁴ The main targets of these antibodies are donor MHC antigens on the endothelium of peritubular and glomerular capillaries.⁵ AMR is the leading cause of graft failure if there is a donor–host antigenic disparity.⁴ Pathologic Banff classifications requirements are listed here and in Table 90-1.⁶

    • Active AMR (the following four criteria must be met):

      • At least one indicator of AMR activity from Group 1

      • At least one indicator of antibody interaction with tissues from Group 2.

      • At least one indicator of donor-specific antibody (DSA) or equivalents from Group 3

      • No indicators of AMR chronicity from Group 4

  • T-cell-mediated rejection (TCMR): Caused by T-cell recognition of donor MHC molecules and resulting T-cell-derived lymphokines or T-cell-mediated cell lysis.^4,5 Pathologic Banff classifications are listed here.⁶

    • Suspicious (borderline) for acute TCMR – one of the two following criteria:

      • Interstitial inflammation in ≤25% of unscarred cortical parenchyma (i0 or i1) and tubulitis with ≥1 mononuclear cells per tubular cross section (t1, t2, or t3)

      • Interstitial inflammation in >25% of unscarred cortical parenchyma (i2 or i3) and tubulitis with one to four mononuclear cells per tubular cross-section (t1)

    • Acute TCMR IA – Interstitial inflammation in >25% of unscarred cortical parenchyma (i2 or i3) and focal moderate tubulitis with 5–10 mononuclear cells per tubular cross-section (t2)

    • Acute TCMR IB – Interstitial inflammation in >25% of unscarred cortical parenchyma (i2 or i3) and severe tubulitis with >10 mononuclear cells per tubular cross section (t3)

    • Acute TCMR IIA – Mild to moderate intimal arteritis in one or more arterial cross-sections (v1)

    • Acute TCMR IIB – ...