Table 3.

Updated 2015 Banff classification categories

Category 1: Normal biopsy or nonspecific changes
Category 2: Antibody‐mediated changes
Acute/active ABMR	All three features must be present for diagnosis. Biopsies showing histological features plus evidence of current/recent antibody interaction with vascular endothelium or DSA, but not both, may be designated as suspicious for acute/active ABMR. Lesions may be clinically acute or smoldering or may be subclinical; it should be noted if the lesion is C4d‐positive or C4d‐negative, based on the following criteria: Histologic evidence of acute tissue injury, including one or more of the following: Microvascular inflammation (g >0 in the absence of recurrent or de novo glomerulonephritis, and/or ptc >0) Intimal or transmural arteritis (v >0)a Acute thrombotic microangiopathy in the absence of any other cause Acute tubular injury in the absence of any other apparent cause Evidence of current/recent antibody interaction with vascular endothelium, including at least one of the following: Linear C4d staining in peritubular capillaries (C4d2 or C4d3 by IF on frozen sections or C4d >0 by IHC on paraffin sections) At least moderate microvascular inflammation ([g + ptc] ≥2), although in the presence of acute TCMR, borderline infiltrate, or infection; ptc ≥2 alone is not sufficient, and g must be ≥1 Increased expression of gene transcripts in the biopsy tissue indicative of endothelial injury, if thoroughly validated Serologic evidence of DSAs (HLA or other antigens) Biopsies suspicious for ABMR on the basis of meeting criteria 1 and 2 should prompt expedited DSA testing
Chronic active ABMRb	All three features must be present for diagnosis. As with acute/active ABMR, biopsies showing histological features plus evidence of current/recent antibody interaction with vascular endothelium or DSA, but not both, may be designated as suspicious, and it should be noted if the lesion is C4d‐positive or C4d‐negative, based on the criteria listed: Histologic evidence of chronic tissue injury, including one or more of the following: TG (cg >0), if no evidence of chronic thrombotic microangiopathy; includes changes evident by EM only (cg1a; Table 4) Severe peritubular capillary basement membrane multilayering (requires EM)c Arterial intimal fibrosis of new onset, excluding other causes; leukocytes within the sclerotic intima favor chronic ABMR if there is no prior history of biopsy‐proven TCMR with arterial involvement but are not required Evidence of current/recent antibody interaction with vascular endothelium, including at least one of the following: Linear C4d staining in peritubular capillaries (C4d2 or C4d3 by IF on frozen sections, or C4d >0 by IHC on paraffin sections) At least moderate microvascular inflammation ([g + ptc] ≥2), although in the presence of acute TCMR, borderline infiltrate, or infection, ptc ≥2 alone is not sufficient and g must be ≥1 Increased expression of gene transcripts in the biopsy tissue indicative of endothelial injury, if thoroughly validated Serologic evidence of DSAs (HLA or other antigens): Biopsies suspicious for ABMR on the basis of meeting criteria 1 and 2 should prompt expedited DSA testing
C4d staining without evidence of rejection	All three features must be present for diagnosisd Linear C4d staining in peritubular capillaries (C4d2 or C4d3 by IF on frozen sections, or C4d >0 by IHC on paraffin sections) g = 0, ptc = 0, cg = 0 (by light microscopy and by EM if available), v = 0; no TMA, no peritubular capillary basement membrane multilayering, no acute tubular injury (in the absence of another apparent cause for this) No acute cell‐mediated rejection (Banff 1997 type 1A or greater) or borderline changes
Category 3: Borderline changes
Suspicious for acute TCMR	Foci of tubulitis (t1, t2, or t3) with minor interstitial inflammation (i0 or i1) or interstitial inflammation (i2, i3) with mild (t1) tubulitis; retaining the i1 threshold for borderline from Banff 2005 is permitted although this must be made transparent in reports and publications No intimal arteritis (v = 0)
Category 4: TCMR
Acute TCMR Grade	IA. Significant interstitial inflammation (>25% of nonsclerotic cortical parenchyma, i2 or i3) and foci of moderate tubulitis (t2) IB. Significant interstitial inflammation (>25% of nonsclerotic cortical parenchyma, i2 or i3) and foci of severe tubulitis (t3) IIA. Mild to moderate intimal arteritis (v1) with or without interstitial inflammation and tubulitis IIB. Severe intimal arteritis comprising >25% of the luminal area (v2) with or without interstitial inflammation and tubulitis III. Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic inflammation (v3)
Chronic active TCMR	Chronic allograft arteriopathy (arterial intimal fibrosis with mononuclear cell infiltration in fibrosis, formation of neointima); note that such lesions may represent chronic active ABMR as well as TCMR; the latter may also be manifest in the tubulointerstitial compartment
Category 5: Interstitial fibrosis and tubular atrophy
Grade	I. Mild interstitial fibrosis and tubular atrophy (≤25% of cortical area) II. Moderate interstitial fibrosis and tubular atrophy (26–50% of cortical area) III. Severe interstitial fibrosis and tubular atrophy (>50% of cortical area)
Category 6: Other changes not considered to be caused by acute or chronic rejection
	BK virus nephropathy Posttransplant lymphoproliferative disorders Calcineurin inhibitor nephrotoxicity Acute tubular injury Recurrent disease De novo glomerulopathy (other than transplant glomerulopathy) Pyelonephritis Drug‐induced interstitial nephritis

ABMR, antibody‐mediated rejection; cg, glomerular double contours; DSA, donor‐specific antibody; EM, electron microscopy; g, glomerulitis; i, inflammation; IF, immunofluorescence; IHC, immunohistochemistry; ptc, peritubular capillaritis; t, tubulitis; TCMR, T cell–mediated rejection; TG, transplant glomerulopathy; TMA, thrombotic microangiopathy; v, intimal arteritis.

^aIt should be noted that these arterial lesions may be indicative of ABMR, TCMR, or mixed ABMR/TCMR. The v lesions are only scored in arteries having a continuous media with two or more smooth muscle layers.

^bLesions of chronic, active ABMR can range from primarily active lesions with early TG evident only by EM (cg1a) to those with advanced TG and other chronic changes in addition to active microvascular inflammation. In the absence of evidence of current/recent antibody interaction with the endothelium (those features in the second section of Table 3), the term “active” should be omitted; in such cases, DSAs may be present at the time of biopsy or at any previous time after transplantation.

^cSeven or more layers in one cortical peritubular capillary and five or more in two additional capillaries, avoiding portions cut tangentially.

^dThe clinical significance of these findings may be quite different in grafts exposed to anti–blood group antibodies (ABO‐incompatible allografts), in which they do not appear to be injurious to the graft and may represent accommodation; however, with anti‐HLA antibodies, such lesions may progress to chronic ABMR and more outcome data are needed.