Update to Diagnostic Categories for Renal Allograft Biopsies ('97)
Kidney Transplantation

Update of Banff Kidney Components
1. Glomerulitis (g): Complete or partial occlusion of one or more glomerular capillary by leukocyte infiltration and endothelial cell enlargement (BANFF 2013).
Type (Grade)
Histopathological Findings
g0
No glomerulitis.
g1
Glomerulitis in less than 25% of glomeruli.
g2
Segmental or global glomerulitis in 25 to 75% of glomeruli.
g3
Glomerulitis (mostly global) in more than 75% of glomeruli.
2. Interstitial inflammation (i): Mononuclear cell interstitial inflammation in at least 10% of the non-scarred cortex as a threshold for grading (BANFF 1997).
Type (Grade)
Histopathological Findings
i0
No or less than 10% inflammation.
i1
10 to 25% of parenchyma inflamed.
i2
26 to 50% of parenchyma inflamed.
i3
More than 50% of parenchyma inflamed.
  • Note 1. The i-score excludes areas that are fibrotic, subcapsular cortex and adventitia around large veins and lymphatics (see ti scoring). In our experience this leads to significant under grading of late rejection. The fibrosis in these cases is frequently not 'non-specific' but the direct result of a smoldering chronic T-cell mediated rejection, which requires optimization of immunosuppression (see ti scoring).
  • Note 2. The inflammatory cells should consist of T lymphocytes and monocyte/macrophages. If more than 5 to 10% of infiltrate is composed of eosinophils and or plasma cells and or neutrophils an * should be placed by the (i) indicating other possible differential diagnoses such as (hypersensitivity and or infection).
Proposed (optional) scoring of total inflammation in renal allograft to include all cortical tissue: including subcapsular cortex, fibrotic and perivascular areas (BANFF 2007).
Type (Grade)
Histopathological Findings
ti0
No or less than 10% inflammation.
ti1
10 to 25% of parenchyma inflamed.
ti2
26 to 50% of parenchyma inflamed.
ti3
More than 50% of parenchyma inflamed.
  • Note: This proposal first appeared following the BANFF 2007 and incorporation of Ti score into routine reporting of renal transplant biopsies remains an important goal of the Banff Working group.
3. Tubulitis (t): More than one focus with mononuclear cells that have breached the basement membrane and lying beneath or in-between tubular epithelial cells. Graded in the most inflamed tubules (BANFF 1997).
Type (Grade)
Histopathological Findings
t0
No mononuclear cells in tubules.
t1
Foci with 1 to 4 cells/tubular cross section (or 10 tubular cells).
t2
Foci with 5 to 10 cells/tubular cross section.
t3
Foci with more than 10 cells/tubular cross section or presence of at LEAST TWO areas of tubular basement membrane destruction accompanied by i2/i3 inflammation and t2 tubulitis else-where in the biopsy.
  • Note: Tubulitis should not be graded in moderately to severely atrophic tubules, i.e. tubules reduced in caliber by 50% or more.
4. Intimal arteritis (v): Lymphocytic infiltration beneath the endothelium (BANFF 1997).
Type (Grade)
Histopathological Findings
v0
No arteritis.
v1
Mild to moderate intimal arteritis in at least one arterial cross section.
v2
Severe intimal arteritis with at least 25% luminal area lost in at least one arterial cross section.
v3
Transmural arteritis and or arterial fibrinoid change and medial smooth muscle necrosis with lymphocytic infiltrate in vessel.
  • Note 1: Arteriolitis is not officially recognized in the grading of acute rejection, but in our experience is indicative of more refractory rejection and worse outcome.
  • Note 2: Analogous to tubulitis scoring, arteritis is graded in the most severely involved vessel.
  • Note 3: Total number of arteries and inflamed arteries should be recoded.
  • Note 4: Interstitial hemorrhage and infarction are possible manifestations of arteritis and should be denoted with * following the (v) score.
5. Peritubular capillaritis (ptc): Scored only if inflammatory cells are present in more than 10% of cortical peritubular capillaries (BANFF 2007).
Type (Grade)
Histopathological Findings
ptc0
No significant cortical peritubular capillaritis or less than 10% of peritubular capillaries with inflammation.
ptc1
More than 10% of peritubular capillaries with capillaritis, with max 3 to 4 luminal inflammatory cells.
ptc2
More than 10% of peritubular capillaries with capillaritis, with max 5 to 10 luminal inflammatory cells.
ptc3
More than 10% of peritubular capillaries with capillaritis, with more than 10 luminal inflammatory cells.
  • Note 1:Note 1: Inflammation in less than 10% of peritubular capillaries regardless of intensity is considered ptc0.
  • Note 2: ptc should not be scored in medulla, areas of pyelonephritis, adjacent to infarcts or around nodular lymphoid aggregates.
  • Note 3: it should be denoted if ptc is diffuse (more than 50% of peritubular capillaries) or focal (50% or less of peritubular capillaries).
6. Interstitial fibrosis (ci) (BANFF 1997):
Type (Grade)
Histopathological Findings
ci0
Interstitial fibrosis in up-to 5% of cortical area.
ci1
Mild- interstitial fibrosis in 6 to 25% of cortical area.
ci2
Moderate- interstitial fibrosis in 26 to 50% of cortical area.
ci3
Severe- interstitial fibrosis in more than 50% of cortical area.
7. Tubular atrophy (ct) (BANFF 1997):
Type (Grade)
Histopathological Findings
ct0
No tubular atrophy.
ct1
Tubular atrophy in up to 25% of the area of cortical tubules.
ct2
Tubular atrophy involving 26 to 50% of the area of cortical tubules.
ci3
Tubular atrophy in more than 50% of the area of cortical tubules.
8. Chronic transplant glomerulopathy (cg): Basement membrane double contours in one or more capillary loops in the most severely affected glomerulus in a biopsy (BANFF 2013).
Type (Grade)
Histopathological Findings
cg0
No GBM double contours by light microscopy or EM.
cg1a
No GBM double contours by light microscopy but GBM double contours (incomplete or circumferential) in at least three glomerular capillaries by EM with associated endothelial swelling and/or subendothelial electronlucent widening.
cg1b
One or more glomerular capillaries with GBM double contours in one or more nonsclerotic glomerulus by light microscopy (involving less than 25% of peripheral capillary loops).
cg2
Double contours affecting 26 to 50% of peripheral capillary loops in the most affected of non-sclerotic glomeruli.
cg3
Double contours affecting more than 50% of peripheral capillary loops in the most affected of non-sclerotic glomeruli.
  • Note: The BANFF 2013 introduced cg1a and cg1b, the remainder of the component remains unchanged from 1997. The threshold for calling cg was also lowered in 2013 to one or more capillary loops as opposed to the previous threshold of 10% or more of capillary loops in the most severely involved glomerulus. Inflammation in less than 10% of peritubular capillaries regardless of intensity is considered ptc0.
9. Mesangial matrix increase (mm): (at least moderate matrix increase): Moderate mesangial matrix increase is defined as expansion of the matrix in the mesangial interspace between adjacent glomerular capillaries to exceed the width of two mesangial cells in at least two lobules (BANFF 1997).
Type (Grade)
Histopathological Findings
mm0
No mesangial matrix increase.
mm1
Up to 25% of non-sclerotic glomeruli affected.
mm2
26 to 50% of non-sclerotic glomeruli affected.
mm3
50% of non-sclerotic glomeruli affected.
10. Vascular fibrous intimal thickening (cv): Changes specific for chronic rejection include disruption of elastic lamina, inflammatory cells in fibrotic intima, proliferation of myofibroblasts and formation of neointima. Graded in worst affected vessel (BANFF 1997).
Type (Grade)
Histopathological Findings
cv0
No chronic vascular changes.
cv1
Vascular narrowing of up to 25% luminal area by fibrointimal thickening of arteries +/- breach of internal elastic lamina or presence of foam cells or occasional mononuclear cells.
cv2
Increased severity of features described above with 26 to 50% narrowing of vascular luminal area.
cv3
Severe vascular changes with more than 50% narrowing of vascular luminal area.
11. Arteriolar hyalinosis (ah) (BANFF 1997).
Type (Grade)
Histopathological Findings
ah0
No PAS-positive hyalin thickening.
ah1
Mild to moderate PAS-positive hyalin thickening in at least one arteriole.
ah2
Moderate to severe PAS-positive hyalin thickening in more than one arteriole.
ah3
Severe PAS-positive hyalin thickening in many arterioles.
  • Note: New onset hyalinosis especially if nodular may signify cyclosporine toxicity, but donor disease, hypertension, and diabetes mellitus need to be excluded.
Proposed alternative scoring of hyalin arteriolar thickening (aah) (BANFF 2007):
Type (Grade)
Histopathological Findings
aah0
No typical lesions of CNI arteriolopathy.
aah1
Replacement of degenerated smooth muscle cells by hyalin deposits present in only one arteriole, no circumferential involvement.
aah2
Replacement of degenerated smooth muscle cells by hyalin deposits present in more than one arteriole, but no circumferential involvement.
aah3
Replacement of degenerated smooth muscle cells by hyalin deposits with circumferential involvement, independent of the number of arterioles involved.
  • Note: This was adapted by BANFF from Michael Mihatsch system for CNI-arteriolopathy scoring. In a study with three pathologists from the same department, the new grading system for arteriolar hyalinosis improved the Kappa value from 0.52 to 0.67. In other studies Kappa values for arteriolar hyalinosis has been as low as 0.17, in part reflecting the very focal nature of the lesion. Nevertheless, whether an increase in the aah score from 1 to 2 has any clinical significance is unclear. Frequently biopsies with grades aah1 and aah2 are similar in histologic chronicity except for the number of arterioles that show very mild hyaline change. Likewise, biopsies graded as aah3 can contain many vessels with aah0 or aah1 changes, and even vessels with circumferential lesions vary widely in % of arteriolar lumen compromised.
Reference
  1. Solez, K., Axelsen, R. a, Benediktsson, H., Burdick, J. F., Cohen, a H., Colvin, R. B., ... Halloran, P. F. (1993). International standardization of criteria for the histologic diagnosis of renal allograft rejection: the Banff working classification of kidney transplant pathology. Kidney International, 44(2), 411-422. PMID: 8377384.
  2. Racusen, L. C., Solez, K., Colvin, R. B., Bonsib, S. M., Castro, M. C., Cavallo, T., ... Yamaguchi, Y. (1999). The Banff 97 working classification of renal allograft pathology. Kidney International, 55(2), 713-723. PMID: 9987096. doi: 10.1046/j.1523-1755.1999.00299.x.
  3. Bellamy, C. O. C., & Randhawa, P. S. (2000). Arteriolitis in renal transplant biopsies is associated with poor graft outcome. Histopathology, 36(6), 488-492. PMID: 10849089.
  4. Solez, K., Colvin, R. B., Racusen, L. C., Sis, B., Halloran, P. F., Birk, P. E., ... Weening, J. J. (2007). Banff '05 meeting report: Differential diagnosis of chronic allograft injury and elimination of chronic allograft nephropathy ("CAN"). American Journal of Transplantation, 7(3), 518-526. PMID: 17352710. doi: 10.1111/j.1600-6143.2006.01688.x.
  5. Solez, K., Colvin, R. B., Racusen, L. C., Haas, M., Sis, B., Mengel, M., ... Valente, M. (2008). Banff 07 classification of renal allograft pathology: Updates and future directions. American Journal of Transplantation, 8(4), 753-760. PMID: 18294345. doi: 10.1111/j.1600-6143.2008.02159.x.
  6. Haas, M., Sis, B., Racusen, L. C., Solez, K., Glotz, D., Colvin, R. B., ... Mengel, M. (2014). Banff 2013 meeting report: Inclusion of C4d-negative antibody-mediated rejection and antibody-associated arterial lesions. American Journal of Transplantation, 14(2), 272-283. PMID: 24472190. doi: 10.1111/ajt.12590.


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