Virchows Archiv

, Volume 469, Issue 5, pp 563–573 | Cite as

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

  • Deján DobiEmail author
  • Zsolt Bodó
  • Éva Kemény
  • László Bidiga
  • Zoltán Hódi
  • Pál Szenohradszky
  • Edit Szederkényi
  • Anikó Szilvási
  • Béla Iványi
Original Article


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.


Renal transplantation Chronic antibody-mediated rejection Peritubular capillaries 


Compliance with ethical standards


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

Conflict of interest

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.

Informed consent

All patients gave their informed consent before the biopsy procedure.


  1. 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):2520–2531CrossRefPubMedGoogle Scholar
  2. 2.
    Drachenberg CB, Papadimitriou JC (2013) Endothelial injury in renal antibody-mediated allograft rejection: a schematic view based on pathogenesis. Transplantation 95(9):1073–1083CrossRefPubMedGoogle Scholar
  3. 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):272–283CrossRefPubMedGoogle Scholar
  4. 4.
    Husain S, Sis B (2013) Advances in the understanding of transplant glomerulopathy. Am J Kidney Dis 62(2):352–363CrossRefPubMedGoogle Scholar
  5. 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):1825–1833CrossRefGoogle Scholar
  6. 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):1129–1138CrossRefPubMedGoogle Scholar
  7. 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):1200–1208CrossRefGoogle Scholar
  8. 8.
    Ivanyi B (2003) Transplant capillaropathy and transplant glomerulopathy: ultrastructural markers of chronic renal allograft rejection. Nephrol Dial Transpl. 18(4):655–660CrossRefGoogle Scholar
  9. 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):269–274CrossRefPubMedGoogle Scholar
  10. 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):889–897CrossRefPubMedGoogle Scholar
  11. 11.
    Terasaki PI, McClelland JD (1964) Microdroplet assay of human serum cytotoxins. Nature 204:998–1000CrossRefPubMedGoogle Scholar
  12. 12.
    Levey AS, Stevens LA, et al. (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150:604–612CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Youden WJ (1950) Index for rating diagnostic tests. Cancer 3(1):32–35CrossRefPubMedGoogle Scholar
  14. 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 67:2089–2100CrossRefPubMedGoogle Scholar
  15. 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):227–233CrossRefPubMedGoogle Scholar
  16. 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):1390–1393CrossRefPubMedGoogle Scholar
  17. 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):620–629CrossRefPubMedPubMedCentralGoogle Scholar
  18. 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):197–204CrossRefPubMedPubMedCentralGoogle Scholar
  19. 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):563–570CrossRefPubMedPubMedCentralGoogle Scholar
  20. 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):321–330CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Deján Dobi
    • 1
    Email author
  • Zsolt Bodó
    • 1
  • Éva Kemény
    • 1
  • László Bidiga
    • 2
  • Zoltán Hódi
    • 3
  • Pál Szenohradszky
    • 3
  • Edit Szederkényi
    • 3
  • Anikó Szilvási
    • 4
  • Béla Iványi
    • 1
  1. 1.Department of Pathology, Faculty of MedicineUniversity of SzegedSzegedHungary
  2. 2.Department of Pathology, Faculty of MedicineUniversity of DebrecenDebrecenHungary
  3. 3.Department of Surgery, Faculty of MedicineUniversity of SzegedSzegedHungary
  4. 4.Transplantation Immunogenetics LaboratoryHungarian National Blood Transfusion ServiceBudapestHungary

Personalised recommendations