Skip to main content
SpringerLink
Log in

Histopathological and clinical findings in renal transplants with Banff type II and III acute cellular rejection without tubulointerstitial infiltrates

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

According to the Banff guidelines for renal transplants, pure endothelialitis without any tubulointerstitial infiltrates (with the Banff components v ≥ 1, i0, t0) has to be called acute cellular rejection (ACR). The pathophysiology of this rare lesion abbreviated as v_only is currently unclear, as well as its clinical, serological, and prognostic implications. Therefore, we conducted this retrospective comparative study. We compared all 23 biopsies with v_only from Hannover Medical School between 2003 and 2010 with 23 matched biopsies with the Banff components v ≥ 1, i ≥ 1, and t ≥ 1 (v_plus) and 23 biopsies with v0, i0, and t0 (v0i0t0). Serological (available in 10, 11, and 14 patients, respectively), histological, and clinical data were compared. Of all biopsies, 0.4 % had findings of v_only. v_only, v_plus, and v0i0t0 only showed minimal differences in the Banff components apart from the cohort-defining components. Endothelialitis in v_only more frequently involved the arcuate arteries than the smaller preglomerular vessels compared to v_plus and vice versa. Combining histopathological data and serological data, v_only more frequently showed criteria for acute humoral rejection than v0i0t0 (albeit not persistent after the Bonferroni–Holm correction in pairwise comparisons), while there was no difference between v_only and v_plus. No difference could be demonstrated regarding clinical presentation at biopsy or outcome. Our results show minimal differences regarding clinical presentation, outcome, and histological features between v_only and v_plus. Patients with v_only should be thoroughly investigated for evidence of acute humoral rejection.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Fleiner F, Glander P, Fritsche L, Neumayer HH, Budde K (2010) Why rejections are not biopsy proven: frequency and reasons. Transplant Proc 42:4509–4512. doi:10.1016/j.transproceed.2010.09.158

    Article  PubMed  CAS  Google Scholar 

  2. Racusen LC, Colvin RB, Solez K, Mihatsch MJ, Halloran PF, Campbell PM, Cecka MJ, Cosyns JP, Demetris AJ, Fishbein MC, Fogo A, Furness P, Gibson IW, Glotz D, Hayry P, Hunsickern L, Kashgarian M, Kerman R, Magil AJ, Montgomery R, Morozumi K, Nickeleit V, Randhawa P, Regele H, Seron D, Seshan S, Sund S, Trpkov K (2003) Antibody-mediated rejection criteria—an addition to the Banff 97 classification of renal allograft rejection. Am J Transplant 3:708–714

    Article  PubMed  Google Scholar 

  3. Racusen LC, Solez K, Colvin RB, Bonsib SM, Castro MC, Cavallo T, Croker BP, Demetris AJ, Drachenberg CB, Fogo AB, Furness P, Gaber LW, Gibson IW, Glotz D, Goldberg JC, Grande J, Halloran PF, Hansen HE, Hartley B, Hayry PJ, Hill CM, Hoffman EO, Hunsicker LG, Lindblad AS, Yamaguchi Y et al (1999) The Banff 97 working classification of renal allograft pathology. Kidney Int 55:713–723

    Article  PubMed  CAS  Google Scholar 

  4. Sis B, Mengel M, Haas M, Colvin RB, Halloran PF, Racusen LC, Solez K, Baldwin WM 3rd, Bracamonte ER, Broecker V, Cosio F, Demetris AJ, Drachenberg C, Einecke G, Gloor J, Glotz D, Kraus E, Legendre C, Liapis H, Mannon RB, Nankivell BJ, Nickeleit V, Papadimitriou JC, Randhawa P, Regele H, Renaudin K, Rodriguez ER, Seron D, Seshan S, Suthanthiran M, Wasowska BA, Zachary A, Zeevi A (2010) Banff '09 meeting report: antibody mediated graft deterioration and implementation of Banff working groups. Am J Transplant 10:464–471. doi:10.1111/j.1600-6143.2009.02987.x

    Article  PubMed  CAS  Google Scholar 

  5. Colvin RB, Cohen AH, Saiontz C, Bonsib S, Buick M, Burke B, Carter S, Cavallo T, Haas M, Lindblad A, Manivel JC, Nast CC, Salomon D, Weaver C, Weiss M (1997) Evaluation of pathologic criteria for acute renal allograft rejection: reproducibility, sensitivity, and clinical correlation. J Am Soc Nephrol 8:1930–1941

    PubMed  CAS  Google Scholar 

  6. Bates WD, Davies DR, Welsh K, Gray DW, Fuggle SV, Morris PJ (1999) An evaluation of the Banff classification of early renal allograft biopsies and correlation with outcome. Nephrol Dial Transplant 14:2364–2369

    Article  PubMed  CAS  Google Scholar 

  7. Mauiyyedi S, Crespo M, Collins AB, Schneeberger EE, Pascual MA, Saidman SL, Tolkoff-Rubin NE, Williams WW, Delmonico FL, Cosimi AB, Colvin RB (2002) Acute humoral rejection in kidney transplantation: II. Morphology, immunopathology, and pathologic classification. J Am Soc Nephrol 13:779–787

    PubMed  Google Scholar 

  8. Trpkov K, Campbell P, Pazderka F, Cockfield S, Solez K, Halloran PF (1996) Pathologic features of acute renal allograft rejection associated with donor-specific antibody, analysis using the Banff grading schema. Transplantation 61:1586–1592

    Article  PubMed  CAS  Google Scholar 

  9. Lefaucheur C, Loupy A, Vernerey D, Duong-Van-Huyen JP, Suberbielle C, Anglicheau D, Verine J, Beuscart T, Nochy D, Bruneval P, Charron D, Delahousse M, Empana JP, Hill GS, Glotz D, Legendre C, Jouven X (2013) Antibody-mediated vascular rejection of kidney allografts: a population-based study. Lancet 381:313–319. doi:10.1016/S0140-6736(12)61265-3

    Article  PubMed  CAS  Google Scholar 

  10. Sis B, Einecke G, Chang J, Hidalgo LG, Mengel M, Kaplan B, Halloran PF (2010) Cluster analysis of lesions in nonselected kidney transplant biopsies: microcirculation changes, tubulointerstitial inflammation and scarring. Am J Transplant 10:421–430. doi:10.1111/j.1600-6143.2009.02938.x

    Article  PubMed  CAS  Google Scholar 

  11. Famulski KS, Einecke G, Sis B, Mengel M, Hidalgo LG, Kaplan B, Halloran PF (2010) Defining the canonical form of T-cell-mediated rejection in human kidney transplants. Am J Transplant 10:810–820. doi:10.1111/j.1600-6143.2009.03007.x

    Article  PubMed  CAS  Google Scholar 

  12. Shimizu T, Tanabe T, Shirakawa H, Omoto K, Ishida H, Tanabe K (2012) Acute vascular rejection after renal transplantation and isolated v-lesion. Clin Transplant 26(Suppl 24):2–8. doi:10.1111/j.1399-0012.2012.01673.x

    Article  PubMed  Google Scholar 

  13. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modif Diet Renal Dis Study Group Ann Intern Med 130:461–470

    CAS  Google Scholar 

  14. World Medical Association (2008) WMA Declaration of Helsinki—ethical principles for medical research involving human subjects. http://www.wma.net/en/30publications/10policies/b3/index.html. Accessed 1 Jan 2012

  15. de Freitas DG, Sellares J, Mengel M, Chang J, Hidalgo LG, Famulski KS, Sis B, Einecke G, Halloran PF (2012) The nature of biopsies with “borderline rejection” and prospects for eliminating this category. Am J Transplant 12:191–201. doi:10.1111/j.1600-6143.2011.03784.x

    Article  PubMed  CAS  Google Scholar 

  16. Halloran PF, Pereira AB, Chang J, Matas A, Picton M, De Freitas D, Bromberg J, Seron D, Sellares J, Einecke G, Reeve J (2013) Potential impact of microarray diagnosis of T cell-mediated rejection in kidney transplants: the INTERCOM study. Am J Transplant 13:2352–2363. doi:10.1111/ajt.12387

    Article  PubMed  CAS  Google Scholar 

  17. Mueller TF, Einecke G, Reeve J, Sis B, Mengel M, Jhangri GS, Bunnag S, Cruz J, Wishart D, Meng C, Broderick G, Kaplan B, Halloran PF (2007) Microarray analysis of rejection in human kidney transplants using pathogenesis-based transcript sets. Am J Transplant 7:2712–2722. doi:10.1111/j.1600-6143.2007.02005.x

    Article  PubMed  CAS  Google Scholar 

  18. Reeve J, Sellares J, Mengel M, Sis B, Skene A, Hidalgo L, de Freitas DG, Famulski KS, Halloran PF (2013) Molecular diagnosis of T cell-mediated rejection in human kidney transplant biopsies. Am J Transplant 13:645–655. doi:10.1111/ajt.12079

    Article  PubMed  CAS  Google Scholar 

  19. Sun Q, Liu Z, Chen J, Chen H, Wen J, Cheng D, Li L (2008) Circulating anti-endothelial cell antibodies are associated with poor outcome in renal allograft recipients with acute rejection. Clin J Am Soc Nephrol 3:1479–1486. doi:10.2215/cjn.04451007

    Article  PubMed Central  PubMed  Google Scholar 

  20. Mengel M, Sis B, Haas M, Colvin RB, Halloran PF, Racusen LC, Solez K, Cendales L, Demetris AJ, Drachenberg CB, Farver CF, Rodriguez ER, Wallace WD, Glotz D (2012) Banff 2011 meeting report: new concepts in antibody-mediated rejection. Am J Transplant 12:563–570. doi:10.1111/j.1600-6143.2011.03926.x

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  21. Hill GS, Nochy D, Bruneval P, Duong van Huyen JP, Glotz D, Suberbielle C, Zuber J, Anglicheau D, Empana JP, Legendre C, Loupy A (2011) Donor-specific antibodies accelerate arteriosclerosis after kidney transplantation. J Am Soc Nephrol 22:975–983. doi:10.1681/ASN.2010070777

    Article  PubMed Central  PubMed  Google Scholar 

  22. Boegehold MA (1998) Heterogeneity of endothelial function within the circulation. Curr Opin Nephrol Hypertens 7:71–78

    Article  PubMed  CAS  Google Scholar 

  23. Ghitescu L, Robert M (2002) Diversity in unity: the biochemical composition of the endothelial cell surface varies between the vascular beds. Microsc Res Tech 57:381–389. doi:10.1002/jemt.10091

    Article  PubMed  CAS  Google Scholar 

  24. Kumar S, West DC, Ager A (1987) Heterogeneity in endothelial cells from large vessels and microvessels. Differentiation 36:57–70

    Article  PubMed  CAS  Google Scholar 

  25. Kobayashi N, Sakai T (1993) Heterogeneity in the distribution of actin filaments in the endothelial cells of arteries and arterioles in the rat kidney. Eur J Cell Biol 60:57–66

    PubMed  CAS  Google Scholar 

Download references

Conflict of interest

The authors have nothing to declare.

Author information

Authors and Affiliations

  1. Institute of Pathology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany

    Verena Bröcker, Clemens Luitpold Bockmeyer, Juliane Wittig, Stephanie Zell & Jan Ulrich Becker

  2. Klinikum Region Hannover Krankenhaus Oststadt-Heidehaus, Medizinische Klinik I, Hannover, Germany

    Muhannad Hirzallah

  3. Clinic for Nephrology and Hypertension, Hannover Medical School, Hannover, Germany

    Wilfried Gwinner, Putri Andina Agustian & Anke Schwarz

  4. Institute of Virology, Hannover Medical School, Hannover, Germany

    Tina Ganzenmüller

  5. Institute of Transfusion Medicine, Hannover Medical School, Hannover, Germany

    Eva Zilian & Stephan Immenschuh

  6. Department of Histopathology, Addenbrooke’s Hospital, Cambridge, UK

    Verena Bröcker

Authors
  1. Verena Bröcker
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Muhannad Hirzallah
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wilfried Gwinner
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Clemens Luitpold Bockmeyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Juliane Wittig
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Stephanie Zell
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Putri Andina Agustian
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Anke Schwarz
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Tina Ganzenmüller
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Eva Zilian
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Stephan Immenschuh
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Jan Ulrich Becker
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jan Ulrich Becker.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bröcker, V., Hirzallah, M., Gwinner, W. et al. Histopathological and clinical findings in renal transplants with Banff type II and III acute cellular rejection without tubulointerstitial infiltrates. Virchows Arch 464, 203–211 (2014). https://doi.org/10.1007/s00428-013-1487-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-013-1487-0

Keywords

Search

Navigation