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Morphologic Features and Clinical Impact of Arteritis Concurrent with Transplant Glomerulopathy

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Pathology & Oncology Research

Abstract

Little is known about the morphology and clinical relevance of arteritis in renal allograft biopsies with transplant glomerulopathy. We retrospectively reviewed the morphologic findings and clinical course of 59 patients with cg, 16 of which featured concurrent arteritis (fibrosing intimal arteritis with luminal narrowing in 15, and acute intimal arteritis in 1 case). Fifteen out of the 16 cases with arteritis fulfilled the morphological diagnostic criteria for chronic active antibody-mediated rejection, and 11 cases with arteritis showed morphological evidence of concurrent, ongoing T-cell-mediated alloimmune response (acute T-cell-mediated rejection in 5, borderline changes in 6 cases). Further, the Banff grades of interstitial inflammation in scarred and nonscarred cortex, total cortical inflammation, and arterial luminal narrowing were significantly higher in biopsies with arteritis. By immunohistochemistry, T-lymphocyte predominance over macrophages was found in the intimal infiltrates in 14 out of 16 cases, and cytotoxic T-lymphocytes were identified among intimal mononuclears in 10 cases. Patients with arteritis demonstrated a significantly shorter renal survival (7.5 vs. 29 months). In conclusion, T-cell-mediated mechanisms could play a role in the development of arteritis concurrent with cg. However, this finding does not exclude the possibility that antibody-mediated rejection can also contribute to the evolution of the lesion. Importantly, the lesion carries negative prognostic value likely via severe arterial luminal narrowing.

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References

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

    Article  CAS  PubMed  Google Scholar 

  2. Matheson PJ, Dittmer ID, Beaumont BW, Merrilees MJ, Pilmore HL (2005) The macrophage is the predominant inflammatory cell in renal allograft intimal arteritis. Transplantation 79:1658–1662

    Article  PubMed  Google Scholar 

  3. Kozakowski N, Böhmig GA, Exner M et al (2009) Monocytes/macrophages in kidney allograft intimal arteritis: no association with markers of humoral rejection or with inferior outcome. Nephrol Dial Transplant 24:1979–1986

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Sun H, Zhou T, Wang Y et al (2011) Macrophages and T lymphocytes are the predominant cells in intimal arteritis of resected renal allografts undergoing acute rejection. Transplant Immunol 25:42–48

    Article  CAS  Google Scholar 

  5. Solez K, Colvin RB, Racusen LC et al (2006) Banff’05 meeting report: differential diagnosis of chronic allograft injury and elimination of chronic allograft nephropathy (‘CAN’). Am J Transplant 7:1–9

    Google Scholar 

  6. Mauiyyedi S, Della Pelle P, Saidman S et al (2001) Chronic humoral rejection: identification of antibody-mediated chronic renal allograft rejection by C4d deposits in peritubular capillaries. J Am Soc Nephrol 12:574–582

    CAS  PubMed  Google Scholar 

  7. Wu KY, Budde K, Schmidt D et al (2014) Acute cellular rejection with isolated v-lesions is not associated with more favorable outcomes than vascular rejection with more tubulointerstitial inflammations. Clin Transpl 28:410–418

    Article  CAS  Google Scholar 

  8. Lefaucheur C, Loupy A, Vernerey D et al (2013) Antibody-mediated vascular rejection of kidney allografts: a population-based study. Lancet 381:313–319

    Article  CAS  PubMed  Google Scholar 

  9. Remport A, Ivanyi B, Mathe Z, Tinckam K, Mucsi I, Molnar MZ (2014) Better understanding of transplant glomerulopathy secondary to chronic antibody-mediated rejection. Nephrol Dial Transplant

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

    Article  CAS  PubMed  Google Scholar 

  11. Ivanyi 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 31:1129–1138

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  13. Racusen LC, Solez K, Colvin RB et al (1999) The Banff 97 working classification of renal allograft pathology. Kidney Int 55:713–723

    Article  CAS  PubMed  Google Scholar 

  14. Solez K, Colvin RB, Racusen LC et al (2008) Banff 07 classification of renal allograft pathology: updates and further directions. Am J Transplant 8:753–760

    Article  CAS  PubMed  Google Scholar 

  15. Batal I, Lunz JG 3rd, Aggrawal N et al (2010) A critical appraisal of methods to grade transplant glomerulitis in renal allograft biopsies. Am J Transplant 10:2442–2452

    Article  CAS  PubMed  Google Scholar 

  16. Mengel M, Reeve J, Bunnag S, Einecke G, Jhangri GS, Sis B, Famulski K, Guembes-Hidalgo L, Halloran PF (2009) Scoring total inflammation is superior to the current Banff inflammation score in predicting outcome and the degree of molecular disturbance in renal allografts. Am J Transplant 9:1859–1867

    Article  CAS  PubMed  Google Scholar 

  17. Sellarés J, de Freitas DG, Mengel M et al (2011) Inflammation lesions in kidney transplant biopsies: associations with survival is due to the underlying diseases. Am J Transplant 11:489–499

    Article  PubMed  Google Scholar 

  18. Hall BM, Bishop GA, Duggin GG, Horvath JS, Philips J, Tiller DJ (1984) Increased expression of HLA-DR antigens on renal tubular cells in renal transplants: relevance to the rejection response. 2(8397):247–251

  19. Nickeleit V, Andreoni K (2007) The classification and treatment of antibody-mediated renal allograft injury: where do we stand? Kidney Int 71:7–11

    Article  CAS  PubMed  Google Scholar 

  20. Wen J, Zhang M, Chen J, Zeng C, Cheng D, Liu ZH (2013) HLA-DR overexpression in tubules of renal allografts during early and late renal allograft injuries. Exp Clin Transplant 11:499–506

    Article  PubMed  Google Scholar 

  21. Sis B, Einecke G, Chang J et al (2010) Cluster analysis of lesions in nonselected kideney transplant biopsies: microcirculation changes, tubulointerstitial inflammation and scarring. Am J Transplant 10:421–430

    Article  CAS  PubMed  Google Scholar 

  22. 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. Modification of Diet in Renal Disease Study Group. Ann Intern Med 130:461–470

    Article  CAS  PubMed  Google Scholar 

  23. 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 

  24. Satoskar AA, Pelletier R, Adams P et al (2010) De novo thrombotic microangiopathy in renal allograft biopsies – role of antibody-mediated rejection. Am J Transplant 10:1804–1811

    Article  CAS  PubMed  Google Scholar 

  25. Baid-Agrawal S, Farris AB III, Pascal M et al (2011) Overlapping pathways to transplant glomerulopathy: chronic humoral rejection, hepatitis C infection, and thrombotic microangiopathy. Kidney Int 80:879–885

    Article  PubMed  Google Scholar 

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Acknowledgments

Supported by TÁMOP grant 4.2.2.A-11/1/KONV-2012-0035 to B.I.

The authors are grateful to Katalin Virág, a PhD student at the Department of Medical Physics and Informatics, University of Szeged, Szeged, Hungary, for her valuable comments.

Disclosure

The authors declare that they have no conflict of interest. Elements of this study were presented at the 25th European Congress of Pathology held in Lisbon, Portugal, from August 31 to September 4, 2013.

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Correspondence to Deján Dobi.

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Dobi, D., Bodó, Z., Kemény, É. et al. Morphologic Features and Clinical Impact of Arteritis Concurrent with Transplant Glomerulopathy. Pathol. Oncol. Res. 22, 15–25 (2016). https://doi.org/10.1007/s12253-015-9962-3

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  • DOI: https://doi.org/10.1007/s12253-015-9962-3

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