Kidney and Liver Transplant - Update and Issues
Classifications and Schemas
Arthur H. Cohen, Juan Lechago and Cynthia C. Nast
Over the course of many years, various systems have been suggested to standardize
pathology of rejection. Although the initial ones had merit, they did not gain widespread acceptance.
In the early 1990s Solez led an effort to develop a schema which would be applicable to multicenter drug
trials and also could potentially be used for diagnostic purposes; as the conferences to establish
criteria, quantitative methods, etc. were held in Banff, Alberta, Canada, the resulting formulation is
known as the Banff Working Schema. Its main emphasis was on acute rejection, although information on
chronic rejection and other changes were components. First published in 1993, it initially gained
acceptance although it soon became readily evident that certain major deficiencies existed and several
subsequent meetings were held to modify the original formulation. Shortly after the original
publication, pathologists involved in an NIH funded multicenter study evaluating novel immunosuppression
strategies, known as Cooperative Clinical Trials in Transplantation (CCTT), devised a standardized
scoring system largely for acute rejection. This proved to be simple to use, highly reproducible with
good sensitivity and specificity and to avoid the deficiencies of the early Banff formulation. The
latest version of the Banff schema, known as Banff 97, incorporated the major components of CCTT thereby
resulting in a more useful classification. The individual features of this schema are too lengthy to
report here in detail; the reader is referred to the literature. Banff '97 has been updated to include
more precise information, characterization and classification of antibody-mediated rejection; this was
done to include C4d-associated acute rejection as a specific category.
The Banff schema has two different components: diagnostic criteria and quantitation of
the abnormalities. The former were established to provide standardization of morphologic features
necessary for the various rejection categories. Although currently reasonably well accepted with the
above mentioned major modifications for acute rejection, the category of Borderline changes is still most
controversial and perhaps unsettling. Several studies have indicated that biopsies with borderline
changes clinically progressed to and/or therapeutically responded as acute rejection in from 30 to 88% of
instances. This calls into question the necessity of this category and its criteria for inclusion. The
issue of borderline changes and their significance in renal transplant s represent a continuing challenge
to the Banff schema . Recent work (Gaber, 2004) indicates and confirms that many biopsies with these
features really represent acute rejection; those that did not respond to increased immunosuppression
often had additional changes such as chronic rejection.
The other aspect of Banff is to provide quantitation of the observed abnormalities. This
has two functions: 1) to establish criteria for grading the degree of severity of the diagnostic
categories and 2) to provide uniformity of observations, especially for use in multicenter studies.
Although some transplant pathologists strictly adhere to the quantitative aspects, many prefer to use
their experience and art of pathology to establish both diagnoses and to grade severity. Nevertheless
most experience with Banff and emphasis to date has been in the realm of acute rejection.
For chronic rejection, while the Banff schema has some merit, the CADI system (chronic
allograft damage index) scores certain changes and has been shown to provide some prognostic
information. Components scored include interstitial fibrosis, tubular atrophy, glomerular sclerosis,
mesangial expansion, glomerular capillary wall double contours and arterial intimal thickening. In
general, the sum score of biopsies performed at 2 years correlated reasonably well with function at 6
years and a high score including interstitial lymphocytes at 6 months correlated well with graft loss at
2 to 3 years post transplantation.
Similar to experience with kidney transplants, classification schemas for liver
transplants have also been developed with, until recently, modest but not widely accepted success.
Spurred on by the concept of Banff for kidneys, in the mid-1990s liver transplant physicians met at Banff
for their own formulation. Following a series of sessions and modifications, the Banff Schema for
Grading Liver Allograft Rejection was created. In contrast to the renal document, the hepatic
formulation and diagnostic criteria have gained more widespread acceptance, especially for acute
rejection and are widely used for diagnostic and therapeutic purposes. On the other hand, quantitation
of the lesions is less commonly used.
For pathologies in both kidney and liver transplants, the concept and use of a
classification schema such as Banff certainly are very attractive for multicenter studies. Their use as
sets of diagnostic criteria is less attractive as the art of pathology may sometimes play as important a
role as quantitative criteria and scientific dogma in establishing diagnoses. As with other quantitative
and semi-quantitative systems designed to score microscopic pathologic changes, the Banff schema has been
shown to be less than reliable. This is largely because of considerable interobserver variability,
especially when the systems are considered on an international basis as Banff is meant to be used. Even
among experienced renal pathologists, variations may be great especially if criteria for specimen
adequacy are misinterpreted.
- Banff schema for grading liver allograft rejection: an international consensus document, Hepatology 25:658-663, 1997.
- Bates WD, Davies DR, Welsh K, Gray DW, Fuggle SV, Morris PJ. An evaluation of the Banff classification of early renal allograft biopsies and correlation with outcome. Nephrol Dial Transplant 14:2364-2369, 1999.
- Colvin RB, Cohen AH, Saiontz C, Bonsib S, Buck M, Burke B, Carter S, Cavallo T, Hass M, Lindblad A, Manivel J, Nast CC, Salomon D, Weaver C, Weiss M. Evaluation of pathologic criteria for acute renal allograft rejection: reproducibility, sensitivity, and clinical correlation. J Am Soc Nephrol 8:1930-1941, 1997.
- Demetris A, Adams D, Bellamy C, Blakolmer K, Clouston A, Dhillon AP et al. Update of the International Banff Schema for Liver Allograft Rejection: working recommendations for the histopathologic staging and reporting of chronic rejection. An international panel. Hepatology 31:792-799, 2000.
- Dimeny E, Wahlberg J, Larsson E, Fellstrom B. Can histopathological findings in early renal allograft biopsies identify patients at risk for chronic vascular rejection? Clin Transplant 9:79-84, 1995.
- Dooper MM, Hoitsma AJ, Koene RA, Bogman MJ. Evaluation of the Banff criteria for the histological diagnosis of rejection in renal allograft biopsies. Transplant Proc 27:1005-6, 1995.
- Furness PN, Taub N. International variation in the interpretation of renal transplant biopsies: report of the CERTPAP project. Kidney Int 60:1998-2012, 2001.
- Furness PN, Taub N, Assmann KJM et al. International variation in histologic grading is large, and persistent feedback does not improve reproducibility. Am J Surg Pathol 27:805-810, 2003.
- Gaber L. Borderline changes in the Banff schema: rejection or no rejection? Transplant Proc 31:755-57, 2004.
- Howie AJ. Problems with Banff. Transplantation 73:1383-1384, 2002.
- Isoniemi H, Nurminen M, Tikkanen MJ, von Willebrand E, et al. Risk factors predicting chronic rejection of renal allografts. Transplant 57:68-72, 1994.
- Isoniemi H, Taskinen E, Hayry P. Histological chronic allograft damage index accurately predicts chronic renal allograft rejection. Transplant 58:1195-8, 1994.
- Kasiske BL, Kalil RS, Lee HS, Rao KV. Histopathologic findings associated with a chronic, progressive decline in renal allograft function. Kidney Int 40:514-24, 1991.
- McCarthy GP, Roberts ISD. Diagnosis of acute renal allograft rejection: evaluation of the Banff '97 guidelines for slide preparation. Transplantation 73:1518-1521, 2002.
- Mueller A, Schnuelle P, Waldherr R, Van Der Woude FJ. Impact of the Banff 97 classification for histological diagnosis of rejection on clinical outcome and renal function parameters after kidney transplantation. Transplantation 69:1123-1127, 2000.
- Ormonde DG, De Boer WB, Kierath A, Bell R, Shilkin KB, House AK, Jeffrey GP, Reed WD. Banff schema for grading liver allograft rejection: utility in clinical practice. Liver Transpl Surg 5:261-268, 1999.
- Racusen LC. The Banff schema and differential diagnosis of allograft dysfunction. Tranplant Proc 36:753-54, 2004.
- Racusen LC, Solez K, Colvin RB et al. The Banff 97 working classification of renal allograft pathology. Kidney Int 55:713-723, 1999.
- Racusen LC, Colvin RB, Solez K et al. Antibody-mediated rejection criteria-an addition to the Banff '97 classification of renal allograft rejection. Am J Transplant 3:708-714, 2003.
- Solez K, Avelsen RA, Benediktsson H, Burdick JF, Cohen AH, Colvin RB, Croker BP, Droz D, Dunnill MS, Halloran PF, et al. International standardization of criteria for the histologic diagnosis of renal allograft rejection: the Banff working classification of kidney transplant pathology. Kidney Int 44:411-422, 1993.