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Peritubular capillary basement membrane multilayering in early and advanced transplant glomerulopathy: quantitative parameters and diagnostic aspects

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Abstract

The ultrastructural quantitative aspects of peritubular capillary basement membrane multilayering (PTCBML) were examined in 57 kidney transplant biopsies with transplant glomerulopathy (TG). The measurements included three cutoffs [permissive: 1 PTC with 5 basement membrane (BM) layers, intermediate: 3 PTCs with 5 layers or 1 PTC with 7 layers, strict: 1 PTC with 7 layers and 2 PTCs with 5 layers] and the mean number of BM layers (PTCcirc). Two groups were assigned, namely patients with mild TG (Banff cg1a and cg1b) and those with moderate-to-severe TG (cg2 and cg3). Their respective clinical, serological, and morphological characteristics were then compared. The clinical data revealed that mild TG corresponded to early chronic antibody-mediated rejection (cABMR), while moderate-to-severe TG corresponded to the advanced stage of the disease. The permissive threshold displayed the lowest specificity (73 %) and the highest sensitivity (83 %) for moderate-to-severe TG, and its corresponding PTCcirc value was 3 layers. In contrast, the strict threshold—adopted by the Banff 2013 classification—displayed a specificity and sensitivity of 93 and 52 %, respectively, and the corresponding PTCcirc was 4 layers. In mild TG, 26 % of the cases met the permissive cutoff and 6 % the strict cutoff. Mild TG was associated with a lower PTCcirc (2.6 layers vs 4.5 layers in moderate-to-severe TG; p < 0.0001). Amongst the various criteria, the permissive criterion was associated most frequently with mild TG, and had prognostic relevance. Because of this, we propose its usage as a marker of early cABMR-induced PTCBML if non-alloimmune causes of PTCBML can be ruled out.

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References

  1. Einecke G, Sis B, Reeve J, Mengel M, et al. (2009) Antibody-mediated microcirculation injury is the major cause of late kidney transplant failure. Am J Transplant 9(11):2520–2531

    Article  CAS  PubMed  Google Scholar 

  2. Drachenberg CB, Papadimitriou JC (2013) Endothelial injury in renal antibody-mediated allograft rejection: a schematic view based on pathogenesis. Transplantation 95(9):1073–1083

    Article  CAS  PubMed  Google Scholar 

  3. Haas M, Sis B, Racusen LC, et al. (2014) Banff 2013 meeting report: inclusion of C4d-negative antibody-mediated rejection and antibody-associated arterial lesions. Am J Transplant 14(2):272–283

    Article  CAS  PubMed  Google Scholar 

  4. Husain S, Sis B (2013) Advances in the understanding of transplant glomerulopathy. Am J Kidney Dis 62(2):352–363

    Article  CAS  PubMed  Google Scholar 

  5. Remport A, Ivanyi B, Mathe Z, Tinckam K, Mucsi I, Molnar MZ (2015) Better understanding of transplant glomerulopathy secondary to chronic antibody-mediated rejection. Nephrol Dial Transpl 30(11):1825–1833

    Article  Google Scholar 

  6. Iványi B, Fahmy H, Brown H, Szenohradszky P, Halloran PF, Solez K (2000) Peritubular capillaries in chronic renal allograft rejection: a quantitative ultrastructural study. Hum Pathol 31(9):1129–1138

    Article  PubMed  Google Scholar 

  7. Ivanyi B, Kemeny E, Szederkenyi E, Marofka F, Szenohradszky P (2001) The value of electron microscopy in the diagnosis of chronic renal allograft rejection. Modern Pathol 14(12):1200–1208

    Article  CAS  Google Scholar 

  8. Ivanyi B (2003) Transplant capillaropathy and transplant glomerulopathy: ultrastructural markers of chronic renal allograft rejection. Nephrol Dial Transpl. 18(4):655–660

    Article  CAS  Google Scholar 

  9. Roufosse CA, Shore I, Moss J, et al. (2012) Peritubular capillary basement membrane multilayering on electron microscopy: a useful marker of early chronic antibody-mediated damage. Transplantation 94(3):269–274

    Article  PubMed  Google Scholar 

  10. de Kort H, Willicombe M, Brookes P, et al. (2016) Peritubular capillary basement membrane multilayering in renal allograft biopsies of patients with de novo donor-specific antibodies. Transplantation 100(4):889–897

    Article  PubMed  Google Scholar 

  11. Terasaki PI, McClelland JD (1964) Microdroplet assay of human serum cytotoxins. Nature 204:998–1000

    Article  CAS  PubMed  Google Scholar 

  12. Levey AS, Stevens LA, et al. (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150:604–612

    Article  PubMed  PubMed Central  Google Scholar 

  13. Youden WJ (1950) Index for rating diagnostic tests. Cancer 3(1):32–35

    Article  CAS  PubMed  Google Scholar 

  14. Levey AS, Eckardt KU, Tsukamoto Y, et al. (2005) Definition and classification of chronic kidney disease: a position statement from kidney disease: improving global outcomes (KDIGO). Kidney Int 67:2089–2100

    Article  PubMed  Google Scholar 

  15. Drachenberg CB, Steinberger E, Hoehn-Saric E, et al. (1997) Specificity of intertubular capillary changes: comparative ultrastructural studies in renal allografts and native kidneys. Ultrastruct Pathol 21(3):227–233

    Article  CAS  PubMed  Google Scholar 

  16. Gough J, Yilmaz A, Miskulin D, et al. (2001) Peritubular capillary basement membrane reduplication in allografts and native kidney disease: a clinicopathologic study of 278 consecutive renal specimens. Transplantation 71(10):1390–1393

    Article  CAS  PubMed  Google Scholar 

  17. Liapis G, Singh HK, Derebail VK, Gasim AM, Kozlowski T, Nickeleit V (2012) Diagnostic significance of peritubular capillary basement membrane multilaminations in kidney allografts: old concepts revisited. Transplantation 94(6):620–629

    Article  PubMed  PubMed Central  Google Scholar 

  18. Haas M, Segev DL, Racusen LC, et al. (2009) C4d depsotion without rejection correlates with reduced early scarring in ABO-incompatible allografts. J Am Soc Nephrol 20(1):197–204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Mengel M, Sis B, Haas M, et al. (2012) Banff 2011 Meeting report: new concepts in antibody-mediated rejection. Am J Transplant 12(3):563–570

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Ivanyi B, Kemeny E, Rago P, et al. (2011) Peritubular capillary basement membrane changes in chronic renal allograft rejection: comparison of light microscopic and ultrastructural observations. Virchows Arch 459(3):321–330

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pathology, Faculty of Medicine, University of Szeged, Állomás utca 1, Szeged, H-6725, Hungary

    Deján Dobi, Zsolt Bodó, Éva Kemény & Béla Iványi

  2. Department of Pathology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, Debrecen, H-4012, Hungary

    László Bidiga

  3. Department of Surgery, Faculty of Medicine, University of Szeged, Szőkefalvi-Nagy u. 6, Szeged, H-6720, Hungary

    Zoltán Hódi, Pál Szenohradszky & Edit Szederkényi

  4. Transplantation Immunogenetics Laboratory, Hungarian National Blood Transfusion Service, Karolina út 19-21, Budapest, H-1113, Hungary

    Anikó Szilvási

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  1. Deján Dobi
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  2. Zsolt Bodó
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  3. Éva Kemény
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  4. László Bidiga
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  5. Zoltán Hódi
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  6. Pál Szenohradszky
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  7. Edit Szederkényi
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  8. Anikó Szilvási
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  9. Béla Iványi
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Correspondence to Deján Dobi.

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The authors declare that they did not have grant funding for the study.

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The authors declare that they have no conflict of interest.

Research involving human participants

This was a retrospective cohort study on human kidney biopsy material taken primarily for diagnostic purposes. During the research process authors reviewed the biopsy material.

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All patients gave their informed consent before the biopsy procedure.

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Dobi, D., Bodó, Z., Kemény, É. et al. Peritubular capillary basement membrane multilayering in early and advanced transplant glomerulopathy: quantitative parameters and diagnostic aspects. Virchows Arch 469, 563–573 (2016). https://doi.org/10.1007/s00428-016-2010-1

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  • DOI: https://doi.org/10.1007/s00428-016-2010-1

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