Skip to main content
SpringerLink
Log in

Practical Renal Allograft Pathology

  • Chapter
  • First Online:
Kidney Transplantation

  • 3068 Accesses

Abstract

Establishment of solid organ transplantation as a routine procedure has required parallel progress in multiple medical and basic science disciplines. Since the 1960s systematic evaluation of transplanted tissue has provided essential information that has helped shape the treatment protocols in use today.

In the early period when graft rejection was the rule rather than the exception, pathology studies could only document the histological features of catastrophic graft loss. Subsequently, accumulation of morphological knowledge has led to a much better understanding of rejection reactions and to the development of sophisticated morphological classifications, such as the Banff schema.

Although acknowledging the complexity and interconnectedness of the immune system, allograft rejection is schematically divided into antibody-mediated rejection (AMR) and T-cell-mediated rejection (CMR).

AMR results from circulating antidonor antibodies which—in conjunction with complement and other secondary mediators—target vascular structures with a predilection for the microvasculature leading to capillary inflammation and injury. Staining for the C4d fragment helps identify cases of AMR by demonstrating this complement component in the microvasculature. CMR, on the other hand, is characterized by interstitial accumulation of inflammatory cells including abundant T-cell infiltrates that preferentially target the renal tubules but can also involve vascular structures. Emphasizing the distinctive features of AMR and CMR helps define a list of morphological differential diagnoses that correspond to each of these processes.

Numerous other processes independent of alloimmunity can result in acute and/or chronic allograft injury that manifest with their corresponding diagnostic features in KTxBx (kidney transplant biopsies) and also require consideration.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

AIN:

Allergic interstitial nephritis

AMR:

Antibody-mediated rejection

ATN:

Acute tubular necrosis

C4d:

C4d complement fragment

CD3:

Stain for T-cells

CD68:

Stain for macrophages

CMR:

T-cell-mediated rejection

CMV:

Cytomegalovirus

CNI:

Calcineurin inhibitor

DGF:

Delayed graft function

DSA:

Donor-specific antibody

EBV:

Epstein–Barr virus

EM:

Electron microscopy

FSGS:

Focal segmental glomerulosclerosis

GBM:

Glomerular basement membranes

H&E:

Hematoxylin and eosin

HUS:

Hemolytic uremic syndrome

IF:

Immunofluorescence stains

IF/TA:

Interstitial fibrosis/tubular atrophy of no specific etiology

KTxBx:

Kidney transplant biopsies

MAPI:

Maryland aggregate pathology index for donor biopsies

MPGN:

Membranoproliferative glomerulonephritis

MT:

Masson’s trichrome stain

PAMS:

Periodic acid methenamine silver stain (Jones stain)

PAS:

Periodic acid stain

PTC:

Peritubular capillaries

PTLD:

Post-transplant lymphoproliferative disorder

PV:

Polyomavirus

PVN:

Polyomavirus allograft nephropathy

SV40:

Simian virus 40 stain for polyomavirus

TG:

Transplant glomerulopathy

TMA:

Thrombotic microangiopathy

References

  1. Williams WW, Taheri D, Tolkoff-Rubin N, Colvin RB. Clinical role of the renal transplant biopsy. Nat Rev Nephrol. 2012;8(2):110–21 [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t Review].

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  2. Gaston RS, Cecka JM, Kasiske BL, Fieberg AM, Leduc R, Cosio FC, et al. Evidence for antibody-mediated injury as a major determinant of late kidney allograft failure. Transplantation. 2010;90(1): 68–74.

    Article  PubMed  CAS  Google Scholar 

  3. Howell WM, Harmer A, Briggs D, Dyer P, Fuggle SV, Martin S, et al. British Society for Histocompatibility & Immunogenetics and British Transplantation Society guidelines for the detection and characterisation of clinically relevant antibodies in allotransplantation. Int J Immunogenet. 2010;37(6):435–7.

    Article  PubMed  CAS  Google Scholar 

  4. Sis B, Mengel M, Haas M, Colvin RB, Halloran PF, Racusen LC, et al. Banff ‘09 meeting report: antibody mediated graft deterioration and implementation of Banff working groups. Am J Transplant. 2010;10(3):464–71 [Clinical Conference Research Support, Non-U.S. Gov’t].

    Article  PubMed  CAS  Google Scholar 

  5. Racusen LC, Solez K, Colvin RB, Bonsib SM, Castro MC, Cavallo T, et al. The Banff 97 working classification of renal allograft pathology. Kidney Int. 1999;55(2):713–23.

    Article  PubMed  CAS  Google Scholar 

  6. Colvin RB, Cohen AH, Saiontz C, Bonsib S, Buick M, Burke B, et al. Evaluation of pathologic criteria for acute renal allograft rejection: reproducibility, sensitivity, and clinical correlation. J Am Soc Nephrol. 1997;8(12):1930–41 [Comparative Study Multicenter Study Research Support, U.S. Gov’t, P.H.S.].

    PubMed  CAS  Google Scholar 

  7. Sorof JM, Vartanian RK, Olson JL, Tomlanovich SJ, Vincenti FG, Amend WJ. Histopathological concordance of paired renal allograft biopsy cores. Effect on the diagnosis and management of acute rejection. Transplantation. 1995;60(11):1215–9.

    Article  PubMed  CAS  Google Scholar 

  8. Bonsib SM, Reznicek MJ, Wright FH. Renal medulla in the diagnosis of acute cellular rejection. Transplantation. 1989;48(4): 690–2.

    PubMed  CAS  Google Scholar 

  9. Drachenberg CB, Papadimitriou JC, Hirsch HH, Wali R, Crowder C, Nogueira J, et al. Histological patterns of polyomavirus nephropathy: correlation with graft outcome and viral load. Am J Transplant. 2004;4(12):2082–92.

    Article  PubMed  Google Scholar 

  10. Batal I, Girnita A, Zeevi A, Saab BA, Stockhausen S, Shapiro R, et al. Clinical significance of the distribution of C4d deposits in different anatomic compartments of the allograft kidney. Mod Pathol. 2008;21(12):1490–8 [Research Support, N.I.H., Extramural].

    Article  PubMed  CAS  Google Scholar 

  11. Haas M. Pathologic features of antibody-mediated rejection in renal allografts: an expanding spectrum. Curr Opin Nephrol Hypertens. 2012;21(3):264–71.

    Article  PubMed  CAS  Google Scholar 

  12. de Kort H, Willicombe M, Brookes P, Dominy KM, Santos-Nunez E, Galliford JW, et al. Microcirculation inflammation associates with outcome in renal transplant patients with de novo donor-specific antibodies. Am J Transplant. 2013;13(2):485–92.

    Article  PubMed  Google Scholar 

  13. Papadimitriou JC, Drachenberg CB, Munivenkatappa R, Ramos E, Nogueira J, Sailey C, et al. Glomerular inflammation in renal allografts biopsies after the first year: cell types and relationship with antibody-mediated rejection and graft outcome. Transplantation. 2010;90(12):1478–85.

    Article  PubMed  CAS  Google Scholar 

  14. Drachenberg CB, Papadimitriou JC. Polyomavirus-associated nephropathy: update in diagnosis. Transpl Infect Dis. 2006;8(2):68–75 [Review].

    Article  PubMed  CAS  Google Scholar 

  15. Randhawa P, Ho A, Shapiro R, Vats A, Swalsky P, Finkelstein S, et al. Correlates of quantitative measurement of BK polyomavirus (BKV) DNA with clinical course of BKV infection in renal transplant patients. J Clin Microbiol. 2004;42(3):1176–80 [Comparative Study Research Support, Non-U.S. Gov’t Research Support, U.S. Gov’t, P.H.S.].

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  16. Munivenkatappa RB, Schweitzer EJ, Papadimitriou JC, Drachenberg CB, Thom KA, Perencevich EN, et al. The Maryland aggregate pathology index: a deceased donor kidney biopsy scoring system for predicting graft failure. Am J Transplant. 2008;8(11):2316–24 [Research Support, Non-U.S. Gov’t].

    Article  PubMed  CAS  Google Scholar 

  17. Ojo AO, Leichtman AB, Punch JD, Hanson JA, Dickinson DM, Wolfe RA, et al. Impact of pre-existing donor hypertension and diabetes mellitus on cadaveric renal transplant outcomes. Am J Kidney Dis. 2000;36(1):153–9.

    Article  PubMed  CAS  Google Scholar 

  18. Ahmad M, Cole EH, Cardella CJ, Cattran DC, Schiff J, Tinckam KJ, et al. Impact of deceased donor diabetes mellitus on kidney transplant outcomes: a propensity score-matched study. Transplantation. 2009;88(2):251–60 [Research Support, Non-U.S. Gov’t].

    Article  PubMed  Google Scholar 

  19. Huebner TA, Papadimitriou JC, Drachenberg CB, Gonzalez A, Philosophe B, Munivenkatappa R. Frozen section evaluation of preimplantation donor kidneys: application of the Maryland Aggregate Pathology Index. Pathol Case Rev. 2010;15(5):174–9 [Case report].

    Article  Google Scholar 

  20. Valente M, Furian L, Rigotti P. Organ donors with small renal cancer: report of 3 cases. Transplant Proc. 2012;44(7):1846–7.

    Article  PubMed  CAS  Google Scholar 

  21. Lappin DW, Hutchison AJ, Pearson RC, O’Donoghue DJ, Roberts IS. Angiomyolipoma in a transplanted kidney. Nephrol Dial Transplant. 1999;14(6):1574–5 [Case Reports].

    Article  PubMed  CAS  Google Scholar 

  22. Nickeleit V. The pathology of kidney transplantation. In: Ruiz P, editor. Transplantation pathology. New York: Cambridge University Press; 2009. p. 45–110.

    Google Scholar 

  23. Reese PP, Caplan AL, Kesselheim AS, Bloom RD. Creating a medical, ethical, and legal framework for complex living kidney donors. Clin J Am Soc Nephrol. 2006;1(6):1148–53 [Research Support, N.I.H., Extramural].

    Article  PubMed  Google Scholar 

  24. Gaber LW, Gaber AO, Tolley EA, Hathaway DK. Prediction by postrevascularization biopsies of cadaveric kidney allografts of rejection, graft loss, and preservation nephropathy. Transplantation. 1992;53(6):1219–25 [Research Support, Non-U.S. Gov’t].

    Article  PubMed  CAS  Google Scholar 

  25. Liptak P, Kemeny E, Morvay Z, Szederkenyi E, Szenohradszky P, Marofka F, et al. Peritubular capillary damage in acute humoral rejection: an ultrastructural study on human renal allografts. Am J Transplant. 2005;5(12):2870–6 [Research Support, Non-U.S. Gov’t].

    Article  PubMed  CAS  Google Scholar 

  26. Drachenberg CB, Papadimitriou JC. Endothelial injury in renal antibody mediated allograft rejection: a schematic view based on pathogenesis. Transplantation. 2013;95(9):1073–83.

    Article  PubMed  CAS  Google Scholar 

  27. Naesens M, Kuypers DR, Sarwal M. Calcineurin inhibitor nephrotoxicity. Clin J Am Soc Nephrol. 2009;4(2):481–508 [Review].

    PubMed  CAS  Google Scholar 

  28. Barone GW, Gurley BJ, Abul-Ezz SR, Gokden N. Sirolimus-induced thrombotic microangiopathy in a renal transplant recipient. Am J Kidney Dis. 2003;42(1):202–6 [Case Reports].

    Article  PubMed  Google Scholar 

  29. Saikali JA, Truong LD, Suki WN. Sirolimus may promote thrombotic microangiopathy. Am J Transplant. 2003;3(2):229–30 [Case Reports].

    Article  PubMed  Google Scholar 

  30. Stegall MD, Gloor JM. Deciphering antibody-mediated rejection: new insights into mechanisms and treatment. Curr Opin Organ Transplant. 2010;15(1):8–10 [Review].

    Article  PubMed  Google Scholar 

  31. Solez K, Colvin RB, Racusen LC, Haas M, Sis B, Mengel M, et al. Banff 07 classification of renal allograft pathology: updates and future directions. Am J Transplant. 2008;8(4):753–60.

    Article  PubMed  CAS  Google Scholar 

  32. Josephson MA, Chiu MY, Woodle ES, Thistlethwaite JR, Haas M. Drug-induced acute interstitial nephritis in renal allografts: histopathologic features and clinical course in six patients. Am J Kidney Dis. 1999;34(3):540–8.

    Article  PubMed  CAS  Google Scholar 

  33. Noris M, Remuzzi G. Thrombotic microangiopathy after kidney transplantation. Am J Transplant. 2010;10(7):1517–23 [Research Support, Non-U.S. Gov’t].

    Article  PubMed  CAS  Google Scholar 

  34. Buchmann TN, Wolff T, Bachmann A, Guerke L, Steiger J, Mihatsch MJ, et al. Repeat true surveillance biopsies in kidney transplantation. Transplantation. 2012;93(9):908–13 [Comparative Study].

    Article  PubMed  Google Scholar 

  35. Papadimitriou JC, Drachenberg CB, Ramos E, Kukuruga D, Klassen DK, Ugarte R, et al. Antibody-mediated allograft rejection: morphologic spectrum and serologic correlations in surveillance and for cause biopsies. Transplantation. 2013;95(1):128–36.

    Article  PubMed  CAS  Google Scholar 

  36. Issa N, Cosio FG, Gloor JM, Sethi S, Dean PG, Moore SB, et al. Transplant glomerulopathy: risk and prognosis related to anti-human leukocyte antigen class II antibody levels. Transplantation. 2008;86(5):681–5 [Research Support, Non-U.S. Gov’t].

    Article  PubMed  CAS  Google Scholar 

  37. Wiebe C, Gibson IW, Blydt-Hansen TD, Karpinski M, Ho J, Storsley LJ, et al. Evolution and clinical pathologic correlations of de novo donor-specific HLA antibody post kidney transplant. Am J Transplant. 2012;12(5):1157–67 [Research Support, Non-U.S. Gov’t].

    Article  PubMed  CAS  Google Scholar 

  38. Einecke G, Sis B, Reeve J, Mengel M, Campbell PM, Hidalgo LG, et al. Antibody-mediated microcirculation injury is the major cause of late kidney transplant failure. Am J Transplant. 2009;9(11):2520–31 [Research Support, Non-U.S. Gov’t].

    Article  PubMed  CAS  Google Scholar 

  39. Lefaucheur C, Loupy A, Vernerey D, Duong-Van-Huyen JP, Suberbielle C, Anglicheau D, et al. Antibody-mediated vascular rejection of kidney allografts: a population-based study. Lancet. 2013;381(9863):313–9.

    Article  PubMed  CAS  Google Scholar 

  40. Nankivell BJ. Antibody-mediated vascular rejection: relation to causation. Lancet. 2013;381(9863):275–7.

    Article  PubMed  Google Scholar 

  41. Sellares J, de Freitas DG, Mengel M, Reeve J, Einecke G, Sis B, et al. Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence. Am J Transplant. 2012;12(2):388–99 [Comparative Study Multicenter Study Research Support, Non-U.S. Gov’t].

    Article  PubMed  CAS  Google Scholar 

  42. Kasiske BL, Snyder JJ, Gilbertson D, Matas AJ. Diabetes mellitus after kidney transplantation in the United States. Am J Transplant. 2003;3(2):178–85.

    Article  PubMed  Google Scholar 

  43. Baid-Agrawal S, Farris III AB, Pascual M, Mauiyyedi S, Farrell ML, Tolkoff-Rubin N, et al. Overlapping pathways to transplant glomerulopathy: chronic humoral rejection, hepatitis C infection, and thrombotic microangiopathy. Kidney Int. 2011;80(8):879–85.

    Article  PubMed  Google Scholar 

  44. Hariharan S, Smith RD, Viero R, First MR. Diabetic nephropathy after renal transplantation. Clinical and pathologic features. Transplantation. 1996;62(5):632–5.

    Article  PubMed  CAS  Google Scholar 

  45. Cosio FG, Frankel WL, Pelletier RP, Pesavento TE, Henry ML, Ferguson RM. Focal segmental glomerulosclerosis in renal allografts with chronic nephropathy: implications for graft survival. Am J Kidney Dis. 1999;34(4):731–8 [Research Support, U.S. Gov’t, P.H.S.].

    Article  PubMed  CAS  Google Scholar 

  46. Nankivell BJ, Borrows RJ, Fung CL, O’Connell PJ, Allen RD, Chapman JR. Evolution and pathophysiology of renal-transplant glomerulosclerosis. Transplantation. 2004;78(3):461–8 [Research Support, Non-U.S. Gov’t].

    Article  PubMed  Google Scholar 

  47. Hirsch HH, Randhawa P. BK virus in solid organ transplant recipients. Am J Transplant. 2009;9 Suppl 4:S136–46 [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t].

    Article  PubMed  Google Scholar 

  48. Drachenberg CB, Hirsch HH, Ramos E, Papadimitriou JC. Polyomavirus disease in renal transplantation: review of pathological findings and diagnostic methods. Hum Pathol. 2005;36(12):1245–55 [Review].

    Article  PubMed  CAS  Google Scholar 

  49. Drachenberg CB, Hirsch HH, Papadimitriou JC, Gosert R, Wali RK, Munivenkatappa R, et al. Polyomavirus BK versus JC replication and nephropathy in renal transplant recipients: a prospective evaluation. Transplantation. 2007;84(3):323–30 [Comparative Study].

    Article  PubMed  Google Scholar 

  50. Alexiev BA, Randhawa P, Vazquez Martul E, Zeng G, Luo C, Ramos E, et al. BK virus-associated urinary bladder carcinoma in transplant recipients: report of 2 cases, review of the literature, and proposed pathogenetic model. Hum Pathol. 2013;44(5):908–17.

    Article  PubMed  Google Scholar 

  51. Onuigbo M, Haririan A, Ramos E, Klassen D, Wali R, Drachenberg C. Cytomegalovirus-induced glomerular vasculopathy in renal allografts: a report of two cases. Am J Transplant. 2002;2(7):684–8 [Case Reports].

    Article  PubMed  Google Scholar 

  52. Storsley L, Gibson IW. Adenovirus interstitial nephritis and rejection in an allograft. J Am Soc Nephrol. 2011;22(8):1423–7 [Case Reports].

    Article  PubMed Central  PubMed  Google Scholar 

  53. Randhawa PS, Magnone M, Jordan M, Shapiro R, Demetris AJ, Nalesnik M. Renal allograft involvement by Epstein-Barr virus associated post-transplant lymphoproliferative disease. Am J Surg Pathol. 1996;20(5):563–71 [Research Support, Non-U.S. Gov’t].

    Article  PubMed  CAS  Google Scholar 

  54. Fonseca Jr LE, Shapiro R, Randhawa PS. Occurrence of urinary tract infection in patients with renal allograft biopsies showing neutrophilic tubulitis. Mod Pathol. 2003;16(4):281–5 [Comparative Study].

    Article  PubMed  Google Scholar 

  55. Laftavi MR, Weber-Shrikant E, Kohli R, Patel S, Feng L, Said M, et al. Sirolimus-induced isometric tubular vacuolization: a new sirolimus histopathologic manifestation. Transplant Proc. 2010;42(7):2547–50 [Case Reports].

    Article  PubMed  CAS  Google Scholar 

  56. El-Zoghby ZM, Stegall MD, Lager DJ, Kremers WK, Amer H, Gloor JM, et al. Identifying specific causes of kidney allograft loss. Am J Transplant. 2009;9(3):527–35 [Research Support, Non-U.S. Gov’t].

    Article  PubMed  CAS  Google Scholar 

  57. Chapman JR. Chronic calcineurin inhibitor nephrotoxicity-lest we forget. Am J Transplant. 2011;11(4):693–7.

    Article  PubMed  CAS  Google Scholar 

  58. Ekberg H, Johansson ME. Challenges and considerations in diagnosing the kidney disease in deteriorating graft function. Transpl Int. 2012;25(11):1119–28 [Research Support, Non-U.S. Gov’t].

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  59. Matas AJ. Calcineurin inhibitors: short-term friend, long-term foe? Clin Pharmacol Ther. 2011;90(2):209–11.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  60. Randhawa P, Kant J, Shapiro R, Tan H, Basu A, Luo C. Impact of genomic sequence variability on quantitative PCR assays for diagnosis of polyomavirus BK infection. J Clin Microbiol. 2011;49(12):4072–6 [Evaluation Studies Research Support, N.I.H., Extramural].

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  61. Haas M. C4d-negative antibody-mediated rejection in renal allografts: evidence for its existence and effect on graft survival. Clin Nephrol. 2011;75(4):271–8 [Review].

    Article  PubMed  CAS  Google Scholar 

  62. Haas M, Sis B, Racusen LC, Solez K et al. Banff 2013 meeting report: inclusion of c4d-negative antibodymediated rejection and antibody-associated arterial lesions. Am J Transplant. 2014;14(2):272–83.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, University of Maryland School of Medicine, 22 South Greene Street, NBW43, Baltimore, MD, 20201, USA

    Cinthia B. Drachenberg M.D. & John C. Papadimitriou M.D., Ph.D.

Authors
  1. Cinthia B. Drachenberg M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John C. Papadimitriou M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Cinthia B. Drachenberg M.D. .

Editor information

Editors and Affiliations

  1. Department of Nephrology, University of Maryland, Baltimore, Maryland, USA

    Matthew R. Weir

  2. Department of Medicine, Section of Nephrology, University of Illinois, Berwyn, Illinois, USA

    Edgar V. Lerma

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this chapter

Cite this chapter

Drachenberg, C.B., Papadimitriou, J.C. (2014). Practical Renal Allograft Pathology. In: Weir, M., Lerma, E. (eds) Kidney Transplantation. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0342-9_31

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-0342-9_31

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4939-0341-2

  • Online ISBN: 978-1-4939-0342-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation