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2017 Update of Banff Diagnostic Categories for Renal Allograft Biopsies |
| Category 1: Normal or Nonspecific Changes |
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| Category 2: Antibody-Mediated Changes |
| 2a. Active antibody-mediated rejection |
All 3 criteria must be present |
Criterion 1: Evidence of tissue injury to include at least 1 of the following: |
Microvascular inflammation 1 or higher with g>0 and/or ptc>0 if there is no glomerulonephritis |
| Microvascular inflammation 1 or higher with g>0 and ptc >0 if there is borderline inflammation, acute T cell mediated rejection, or infection (note that in these cases ptc>0 alone is not sufficient and g must be at least 1) |
| Any arteritis (v>0) |
| Acute thrombotic microangiopathy in the absence of other causes |
| Acute tubular injury in the absence of other causes |
Criterion 2: Evidence of current or recent antibody: endothelial interaction to include at least 1 of the following: |
Linear C4d staining in peritubular capillaries (C4d2 or C4d3 byimmunofluorescence on frozen section or C4d>0 by paraffin immunohistochemistry) |
| Microvascular inflammation 2 or higher if there is no glomerulonephritis |
| Microvascular inflammation 2 or higher with g>0 if there is borderline inflammation, acute T cell mediated rejection, or infection (note that in these cases ptc >1 alone is not sufficient and g must be at least 1) |
| Increased expression of biopsy-derived gene transcripts or classifiers strongly associated with active antibody mediated rejection, if thoroughly validated. (Molecular testing, although encouraged, is not yet approved for diagnosis) |
Criterion 3: Evidence of donor specific antibody (DSA) or an alternative (substitute) marker to include at least 1 of the following: |
Serologic evidence of donor-specific antibody to HLA or other antigen (e.g. anti-angiotensin type I receptor) |
| Linear C4d staining in peritubular capillaries (C4d2 or C4d3 byimmunofluorescence on frozen section or C4d>0 by paraffin immunohistochemistry) can substitute for DSA. (Note: if criteria 1 and 2 above are met, thorough DSA testing is strongly advised, including non-HLA antibodies if HLA antibody is negative) |
| Increased expression of biopsy-derived gene transcripts or classifiers strongly associated with active antibody mediated rejection, if thoroughly validated, can substitute for DSA. (Note: if Criteria 1 and 2 above are met, thorough DSA testing is strongly advised, including non-HLA antibodies if HLA antibody is negative) (Molecular testing, although encouraged, is not yet approved for diagnosis) |
| 2b. Chronic active antibody-mediated rejection |
All 3 criteria must be present |
Criterion 1: Evidence of chronic tissue injury to include at least 1 of the following: |
Transplant glomerulopathy cg=1 or greater (includes cg1a recognizable by electron microscopy alone) if there is no glomerulonephritis or thrombotic microangiopathy |
| Severe peritubular capillary basement membrane multilayering by electron microscopy (7 or more layers in one cortical peritubular capillary and 5 or more layers in 2 additional capillaries, avoiding tangentially cut areas) |
| Arterial intimal fibrosis of new onset if other causes are excluded (Note: leukocytes in sclerotic intima are helpful to favor this in the absence of a history of T cell mediated rejection but are not necessary) |
| Criterion 2: Evidence of current or recent antibody: endothelial interaction to include at least 1 of the following: |
Linear C4d staining in peritubular capillaries (C4d2 or C4d3 byimmunofluorescence on frozen section or C4d>0 by paraffin immunohistochemistry) |
| Microvascular inflammation 2 or higher if there is no glomerulonephritis |
| Microvascular inflammation 2 or higher with g>0 if there is borderline inflammation, acute T cell mediated rejection, or infection (note that in these cases ptc >1 alone is not sufficient and g must be at least 1) |
| Increased expression of biopsy-derived gene transcripts or classifiers strongly associated with active antibody mediated rejection, if thoroughly validated. (Molecular testing, although encouraged, is not yet approved for diagnosis) |
| Criterion 3: Evidence of donor specific antibody (DSA) or an alternative (substitute) marker to include at least 1 of the following: |
Serologic evidence of donor-specific antibody to HLA or other antigen (e.g. anti-angiotensin type I receptor) |
| Linear C4d staining in peritubular capillaries (C4d2 or C4d3 byimmunofluorescence on frozen section or C4d>0 by paraffin immunohistochemistry) can substitute for DSA. (Note: if criteria 1 and 2 above are met, thorough DSA testing is strongly advised, including non-HLA antibodies if HLA antibody is negative) |
| Increased expression of biopsy-derived gene transcripts or classifiers strongly associated with active antibody mediated rejection, if thoroughly validated, can substitute for DSA. (Note: if Criteria 1 and 2 above are met, thorough DSA testing is strongly advised, including non-HLA antibodies if HLA antibody is negative) (Molecular testing, although encouraged, is not yet approved for diagnosis) |
| 2c. C4d staining without evidence of rejection |
| All 4 criteria must be present |
| Criterion 1: Evidence of current or recent antibody: endothelial interaction: |
Linear C4d staining in peritubular capillaries (C4d2 or C4d3 byimmunofluorescence on frozen section or C4d>0 by paraffin immunohistochemistry) |
| Criterion 2: No evidence of acute or chronic tissue injury (i.e., Criterion 1 for active or chronic active antibody mediated rejection not met). Includes the following: |
Microvascular inflammation = 0 if there is no glomerulonephritis (g=0, ptc=0) |
| No evidence of glomerulitis (g0) if there is borderline inflammation, acute T cell mediated rejection, or infection |
| No evidence of transplant glomerulopathy (cg0) if there is no glomerulonephritis or thrombotic microangiopathy |
| No evidence of arteritis (v0) |
| No evidence of acute thrombotic microangiopathy in the absence of other causes |
| No evidence of acute tubular injury in the absence of other causes |
| No evidence of severe peritubular capillary basement membrane multilayering by electron microscopy (7 or more layers in one cortical peritubular capillary and 5 or more layers in 2 additional capillaries, avoiding tangentially cut areas) |
| No evidence of arterial intimal fibrosis of new onset if other causes are excluded |
| Criterion 3: No molecular evidence for active or chronic active antibody mediated rejection |
No evidence of increased expression of biopsy-derived gene transcripts or classifiers strongly associated with active antibody mediated rejection, if thoroughly validated.(Molecular testing, although encouraged, is not yet approved for diagnosis) |
| Criterion 4: No evidence of borderline changes, acute T cell mediated rejection or chronic active T cell mediated rejection |
Diagnostic features of Categories 3, 4a and 4b are not present |
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| Category 3. Borderline Changes |
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Suspicious (Borderline) for acute T cell mediated rejection (both features must be present) |
Minor interstitial inflammation (i0, i1) with foci of tubulitis (t>0) or moderate to severe interstitial inflammation (i2, i3)with mild tubulitis (t1). (Note: Banff 2005 criteria retaining the i1 threshold for borderline with t>0, i.e., i2 t2 threshold for rejection not met, is permitted but must be noted in reports and publications) |
| No evidence of arteritis (v0) |
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| Category 4. T-cell Mediated Rejection |
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4a. Acute T-cell-mediated rejection |
| Grade |
Diagnostic Features |
| IA |
(i2 or i3) and (t2): interstitial inflammation >25% of nonsclerotic cortical parenchyma with moderate tubulitis involving 1 or more tubules, not counting severely atrophic tubules (severe atrophy = each of the following: a) diameter <25% of unaffected/minimally affected tubules, b) undifferentited appearing flattened or cuboidal epithelium, c) tubular basement membrane with pronounced wrinkling and/or thickening) |
| IB |
(i2 or i3) and (t3): interstitial inflammation >25% of nonsclerotic cortical parenchyma with severe tubulitis involving 1 or more tubules, not counting severely atrophic tubules (severe atrophy = each of the following: a) diameter <25% of unaffected/minimally affected tubules, b) undifferentiated appearing flattened or cuboidal epithelium, c) tubular basement membrane with pronounced wrinkling and/or thickening) |
| IIA |
(v1): mild to moderate intimal arteritis with or without interstitial inflammation, tubulitis (note: arterial lesions can occur in T cell mediated rejection, antibody mediated rejection, or mixed antibody and T cell mediated rejection) |
| IIB |
(v2): severe intimal arteritis with or without interstitial inflammation, tubulitis (note: arterial lesions can occur in T cell mediated rejection, antibody mediated rejection, or mixed antibody and T cell mediated rejection) |
| III |
(v3): transmural arteritis and/or arterial fibrinoid necrosis of media with associated mononuclear cell intimal arteritis with or without interstitial inflammation, tubulitis (note: arterial lesions can occur in T cell mediated rejection, antibody mediated rejection, or mixed antibody and T cell mediated rejection) |
| 4b. Chronic active T-cell-mediated rejection |
Grade |
Diagnostic Features |
| IA |
(ti2 or ti3) and (i-IFTA2 or i-IFTA3) and (t2): Interstitial inflammation >25% of total cortex (ti2, ti3) AND interstitial inflammation >25% of sclerotic cortex (i-IFTA2, i-IFTA3) AND t2 tubulitis in at least one tubule, excluding severely atrophic tubules (severe atrophy = each of the following: a) diameter <25% of unaffected/minimally affected tubules, b) undifferentiated appearing flattened or cuboidal epithelium, c) tubular basement membrane with pronounced wrinkling and/or thickening). Must also exclude other known causes of i-IFTA. |
| IB |
(ti2 or ti3) and (i-IFTA2 or i-IFTA3) and (t3):Interstitial inflammation >25% of total cortex (ti2, ti3) AND interstitial inflammation >25% of sclerotic cortex (i-IFTA2, i-IFTA3) AND t3 tubulitis in at least one tubule, excluding severely atrophic tubules (severe atrophy = each of the following: a) diameter <25% of unaffected/minimally affected tubules, b) undifferentiated appearing flattened or cuboidal epithelium, c) tubular basement membrane with pronounced wrinkling and/or thickening). Must also exclude other known causes of i-IFTA. |
II |
Chronic allograft arteriopathy (arterial intimal fibrosis with mononuclear cell infiltration in fibrosis and formation of neo-intima) |
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Category 5. Interstitial Fibrosis and Tubular Atrophy |
| Grade |
Diagnostic Features |
I |
Mild interstitial fibrosis and tubular atrophy (25% or less of cortical area)
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II |
Moderate interstitial fibrosis and tubular atrophy (26-50% of cortical area)
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| III |
Severe interstitial fibrosis and tubular atrophy/loss (>50% of cortical area) |
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Category 6. Other Changes Not Considered to be Due to Acute or Chronic Rejection |
Diagnosis |
Comments |
| BK virus nephropathy |
See BK and JC virus infection page |
| Posttransplant lymphoproliferative disorders |
See WHO 2017 PTLD Classification page |
| Calcineurin inhibitor nephrotoxicity |
Arteriolar hyalinosis with peripheral hyaline nodules and/or progressive increase in the absence of hypertension or diabetes. Tubular cell injury with isometric vacuolization or lymphatics; see calcineurin toxicity page |
| Acute tubular injury |
See acute tubular necrosis page |
| Recurrent disease |
See pre-existing disease page |
| De novo glomerulopathy other than transplant glomerulopathy |
See de novo glomerulonephritis page |
| Pyelonephritis |
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| Drug induced interstitial nephritis |
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References
- Haas M, Loupy A, Lefaucheur C, Roufosse C, Glotz D, Seron D, Nankivell BJ, Halloran PF, Colvin RB, Akalin E, Alachkar N, Bagnasco S, Bouatou Y, Becker JU, Cornell LD, Duong va Huenn JP, Gibson IW, Kraus ES, Mannon RB, Naesens M, Nickeleit V, Nickerson P, Segev DL, Singh HK, Stegall M, Randhawa P, Racusen L, Solez K, Mengel M. The Banff 2017 kidney meeting report: Revised diagnostic criteria for chronic active T cell-mediated rejection, antibody-mediated rejection, and prospects for integrative endpoints for next-generation clinical trials. Am J Transplant 2018;18:293-307.
- Loupy A, Haas M, Solez K, Racusen L, Glotz D, Seron D, Nankivell BJ, Colvin RB, Afrouzian M, Akalin E, Alachkar N, Bagnasco S, Becker JU, Cornell L, Drachenberg C, Dragun D, de Kort H, Gibson IW, Kraus ES, Lefaucheur C, Legendre C, Liapis H, Muthukumar T, Nickeleit V, Orandi B, Park W, Rabant M, Randhawa P, Reed EF, Roufosse C, Seshan SV, Sis B, Singh HK, Schinstock C, Tambur A, Zeevi Z, Mengel M. The Banff 2015 kidney meeting report: Current challenges in rejection classification and prospects for adopting molecular pathology. Am J Transplant 2017;17:28-41.
- Roufosse C, Simmonds N, Clahsen-van Groningen M, Haas M, Henriksen KJ, Horsfield C, Loupy A, Mengel M, Perkowska-Ptasinska A, Rabant M, Racusen LC, Solez K, Becker JU. A 2018 reference guide to the Banff classification of renal allograft pathology. Transplantation 2018 102(11):1795-1814
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