Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Clinical role of the renal transplant biopsy

Nature Reviews Nephrology volume 8, pages 110–121 (2012)Cite this article

Subjects

Abstract

Percutaneous needle core biopsy is the definitive procedure by which essential diagnostic and prognostic information on acute and chronic renal allograft dysfunction is obtained. The diagnostic value of the information so obtained has endured for over three decades and has proven crucially important in shaping strategies for therapeutic intervention. This Review provides a broad outline of the utility of performing kidney graft biopsies after transplantation, highlighting the relevance of biopsy findings in the immediate and early post-transplant period (from days to weeks after implantation), the first post-transplant year, and the late period (beyond the first year). We focus on how biopsy findings change over time, and the wide variety of pathological features that characterize the major clinical diagnoses facing the clinician. This article also includes a discussion of acute cellular and humoral rejection, the toxic effects of calcineurin inhibitors, and the widely varying etiologies and characteristics of chronic lesions. Emerging technologies based on gene expression analyses and proteomics, the in situ detection of functionally relevant molecules, and new bioinformatic approaches that hold the promise of improving diagnostic precision and developing new, refined molecular pathways for therapeutic intervention are also presented.

Key Points

  • Renal biopsy analysis provides the best means of determining the cause of acute or chronic kidney allograft dysfunction

  • Biopsy results change the pretest diagnosis and recommended treatment in approximately 40% of patients

  • Kidney allograft pathology varies with time after transplantation

  • During the first year after transplantation, a high rate of recurrent kidney disease, as well as de novo glomerular disease and viral nephropathies, can occur

  • Late allograft dysfunction remains a challenging presentation: however, insights into its pathophysiology have been realized since the introduction of disease-specific categorization of pathological findings

  • New technologies are emerging that might lead to profound insights into the mechanisms of allograft dysfunction and the development of precise treatment protocols

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Timing of complications after kidney transplantation in allograft recipients.
Figure 2: Pathological findings in renal biopsy samples taken 0–3 days after transplantation.
Figure 3: Pathological findings observed in renal biopsy samples obtained 3–30 days after transplantation.
Figure 4: Pathological findings observed in renal biopsy samples obtained 1–12 months after transplantation.
Figure 5: Pathological findings observed in renal biopsy samples obtained after the first year post-transplantation.

Similar content being viewed by others

References

  1. Colvin, R. B. et al. Diagnostic Pathology: Kidney Diseases (Amirsys, Salt Lake City, 2011).

    Google Scholar 

  2. Colvin, R. B. & Nickeleit, V. in Heptinstall's Pathology of the Kidney, Vol. 2 (eds Jennette, J. C., Olson, J. L., Schwartz, M. M. & Silva, F. G.) 1347–1490 (Lippincott-Raven, Philadelphia, 2006).

    Google Scholar 

  3. Pascual, M. et al. The clinical usefulness of the renal allograft biopsy in the cyclosporine era: a prospective study. Transplantation 67, 737–741 (1999).

    Article  CAS  PubMed  Google Scholar 

  4. Nickeleit, V. Pathology: donor biopsy evaluation at time of renal grafting. Nat. Rev. Nephrol. 5, 249–251 (2009).

    Article  PubMed  Google Scholar 

  5. Massie, A. B., Desai, N. M., Montgomery R. A., Singer, A. L. & Segev, D. L. Improving distribution efficiency of hard-to-place deceased donor kidneys: predicting probability of discard or delay. Am. J. Transplant. 10, 1613–1620 (2010).

    Article  CAS  PubMed  Google Scholar 

  6. Remuzzi, G. et al. Long-term outcome of renal transplantation from older donors. N. Engl. J. Med. 354, 343–352 (2006).

    Article  CAS  PubMed  Google Scholar 

  7. Munivenkatappa, R. B. et al. The Maryland aggregate pathology index: a deceased donor kidney biopsy scoring system for predicting graft failure. Am. J. Transplant. 8, 2316–2324 (2008).

    Article  CAS  PubMed  Google Scholar 

  8. Perco, P. et al. Histogenomics: association of gene expression patterns with histological parameters in kidney biopsies. Transplantation 87, 290–295 (2009).

    Article  CAS  PubMed  Google Scholar 

  9. Naesens, M. et al. Expression of complement components differs between kidney allografts from living and deceased donors. J. Am. Soc. Nephrol. 20, 1839–1851 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kaminska, D. et al. Cytokine gene expression in kidney allograft biopsies after donor brain death and ischemia-reperfusion injury using in situ reverse-transcription polymerase chain reaction analysis. Transplantation 84, 1118–1124 (2007).

    Article  CAS  PubMed  Google Scholar 

  11. Mueller, T. F. et al. The transcriptome of the implant biopsy identifies donor kidneys at increased risk of delayed graft function. Am. J. Transplant. 8, 78–85 (2008).

    CAS  PubMed  Google Scholar 

  12. Mas, V. R. et al. Distinctive gene expression profiles characterize donor biopsies from HCV-positive kidney donors. Transplantation 90, 1172–1179 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Kainz, A. et al. Gene-expression profiles and age of donor kidney biopsies obtained before transplantation distinguish medium term graft function. Transplantation 83, 1048–1054 (2007).

    Article  CAS  PubMed  Google Scholar 

  14. Kurian, S. M. et al. Laparoscopic donor nephrectomy gene expression profiling reveals upregulation of stress and ischemia associated genes compared to control kidneys. Transplantation 80, 1067–1071 (2005).

    Article  PubMed  Google Scholar 

  15. Schroppel, B. et al. Tubular expression of KIM-1 does not predict delayed function after transplantation. J. Am. Soc. Nephrol. 21, 536–542 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Reeves-Daniel, A. M. et al. The APOL1 gene and allograft survival after kidney transplantation. Am. J. Transplant. 11, 1025–1030 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Chapman, J. R. Longitudinal analysis of chronic allograft nephropathy: clinicopathologic correlations. Kidney Int. Suppl. 99, S108–S112 (2005).

    Article  Google Scholar 

  18. Solez, K. et al. Banff 07 classification of renal allograft pathology: updates and future directions. Am. J. Transplant. 8, 753–760 (2008).

    Article  CAS  PubMed  Google Scholar 

  19. Padiyar, A. et al. Influence of African-American ethnicity on acute rejection after early steroid withdrawal in primary kidney transplant recipients. Transplant. Proc. 42, 1643–1647 (2010).

    Article  CAS  PubMed  Google Scholar 

  20. Grafft, C. A. et al. Antibody-mediated rejection following transplantation from an HLA-identical sibling. Nephrol. Dial. Transplant. 25, 307–310 (2010).

    Article  CAS  PubMed  Google Scholar 

  21. Collins, A. B. et al. Putative antibody-mediated rejection with C4d deposition in HLA-identical, ABO-compatible renal allografts. Transplant. Proc. 38, 3427–3429 (2006).

    Article  CAS  PubMed  Google Scholar 

  22. Haas, M. C4d-negative antibody-mediated rejection in renal allografts: evidence for its existence and effect on graft survival. Clin. Nephrol. 75, 271–278 (2011).

    Article  CAS  PubMed  Google Scholar 

  23. Loupy, A. et al. Significance of C4d Banff scores in early protocol biopsies of kidney transplant recipients with preformed donor-specific antibodies (DSA). Am. J. Transplant. 11, 56–65 (2011).

    Article  CAS  PubMed  Google Scholar 

  24. Seemayer, C. A., Gaspert, A., Nickeleit, V. & Mihatsch, M. J. C4d staining of renal allograft biopsies: a comparative analysis of different staining techniques. Nephrol. Dial. Transplant. 22, 568–576 (2007).

    Article  PubMed  Google Scholar 

  25. Noris, M. & Remuzzi, G. Thrombotic microangiopathy after kidney transplantation. Am. J. Transplant. 10, 1517–1523 (2010).

    Article  CAS  PubMed  Google Scholar 

  26. Satoskar, A. A. et al. De novo thrombotic microangiopathy in renal allograft biopsies—role of antibody-mediated rejection. Am. J. Transplant. 10, 1804–1811 (2010).

    Article  CAS  PubMed  Google Scholar 

  27. Briganti, E. M., Russ, G. R., McNeil, J. J., Atkins, R. C. & Chadban, S. J. Risk of renal allograft loss from recurrent glomerulonephritis. N. Engl. J. Med. 347, 103–109 (2002).

    Article  PubMed  Google Scholar 

  28. Hariharan, S. et al. Recurrent and de novo glomerular disease after renal transplantation: a report from the Renal Allograft Disease Registry (RADR). Transplantation 68, 635–641 (1999).

    Article  CAS  PubMed  Google Scholar 

  29. Angelo, J. R., Bell, C. S. & Braun, M. C. Allograft failure in kidney transplant recipients with membranoproliferative glomerulonephritis. Am. J. Kidney Dis. 57, 291–299 (2011).

    Article  PubMed  Google Scholar 

  30. Wei, C. et al. Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis. Nat. Med. 17, 952–960 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Qin, W. et al. Anti-phospholipase A2 receptor antibody in membranous nephropathy patients. J. Am. Soc. Nephrol. http://dx.doi.org/10.1681/ASN.2010090967.

  32. Beck, L. H. Jr et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N. Engl. J. Med. 361, 11–21 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Randhawa, P. & Brennan, D. C. BK virus infection in transplant recipients: an overview and update. Am. J. Transplant. 6, 2000–2005 (2006).

    Article  CAS  PubMed  Google Scholar 

  34. Drachenberg, C. B. et al. Polyomavirus BK versus JC replication and nephropathy in renal transplant recipients: a prospective evaluation. Transplantation 84, 323–330 (2007).

    Article  PubMed  Google Scholar 

  35. Nickeleit V, S. J. & Mihatsch, M. J. BK virus infection after kidney transplantation. Graft 5 (Suppl.), S46–S57 (2002).

    Article  Google Scholar 

  36. Bracamonte, E. et al. Tubular basement membrane immune deposits in association with BK polyomavirus nephropathy. Am. J. Transplant. 7, 1552–1560 (2007).

    Article  CAS  PubMed  Google Scholar 

  37. Sar, A. et al. Interobserver agreement for polyomavirus nephropathy grading in renal allografts using the working proposal from the 10th Banff Conference on Allograft Pathology. Hum. Pathol. 42, 2018–2024 (2011).

    Article  PubMed  Google Scholar 

  38. Hirsch, H. H. et al. Prospective study of polyomavirus type BK replication and nephropathy in renal-transplant recipients. N. Engl. J. Med. 347, 488–496 (2002).

    Article  PubMed  Google Scholar 

  39. Singh, H. K. et al. Presence of urinary Haufen accurately predicts polyomavirus nephropathy. J. Am. Soc. Nephrol. 20, 416–427 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Han Lee, E. D. et al. A mouse model for polyomavirus-associated nephropathy of kidney transplants. Am. J. Transplant. 6, 913–922 (2006).

    Article  CAS  PubMed  Google Scholar 

  41. Varma, M. C. et al. Early onset adenovirus infection after simultaneous kidney-pancreas transplant. Am. J. Transplant. 11, 623–627 (2011).

    Article  CAS  PubMed  Google Scholar 

  42. Storsley, L. & Gibson, I. W. Adenovirus interstitial nephritis and rejection in an allograft. J. Am. Soc. Nephrol. 22, 1423–1427 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  43. Lamb, K. E., Lodhi, S. & Meier-Kriesche, H. U. Long-term renal allograft survival in the United States: a critical reappraisal. Am. J. Transplant. 11, 450–462 (2011).

    Article  CAS  PubMed  Google Scholar 

  44. Colvin, R. B. Chronic allograft nephropathy. N. Engl. J. Med. 349, 2288–2290 (2003).

    Article  CAS  PubMed  Google Scholar 

  45. Solez, K. et al. Banff '05 Meeting Report: differential diagnosis of chronic allograft injury and elimination of chronic allograft nephropathy ('CAN'). Am. J. Transplant. 7, 518–526 (2007).

    Article  CAS  PubMed  Google Scholar 

  46. El-Zoghby, Z. M. et al. Identifying specific causes of kidney allograft loss. Am. J. Transplant. 9, 527–535 (2009).

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  48. Regele, H. et al. Capillary deposition of complement split product C4d in renal allografts is associated with basement membrane injury in peritubular and glomerular capillaries: a contribution of humoral immunity to chronic allograft rejection. J. Am. Soc. Nephrol. 13, 2371–2380 (2002).

    Article  PubMed  Google Scholar 

  49. Einecke G. et al. Antibody-mediated microcirculation injury is the major cause of late kidney transplant failure. Am. J. Transplant. 9, 2520–2531 (2009).

    Article  CAS  PubMed  Google Scholar 

  50. Gaston, R. S. et al. Evidence for antibody-mediated injury as a major determinant of late kidney allograft failure. Transplantation 90, 68–74 (2010).

    Article  CAS  PubMed  Google Scholar 

  51. Kieran, N. et al. Combination of peritubular c4d and transplant glomerulopathy predicts late renal allograft failure. J. Am. Soc. Nephrol. 20, 2260–2268 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Hill, G. S. et al. Donor specific antibodies accelerate arteriosclerosis after kidney transplantation. J. Am. Soc. Nephrol. 22, 975–983 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  53. Sis, B. et al. Endothelial gene expression in kidney transplants with alloantibody indicates antibody mediated damage despite lack of C4d staining. Am. J. Transplant. 9, 2312–2323 (2009).

    Article  CAS  PubMed  Google Scholar 

  54. Hirohashi, T. et al. Complement independent antibody-mediated endarteritis and transplant arteriopathy in mice. Am. J. Transplant. 10, 510–517 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Hirohashi, T. et al. A novel pathway of chronic allograft rejection mediated by NK cells and alloantibody. Am. J. Transplant. doi:10.1111/j.1600–6143.2011.03836.x).

  56. Hidalgo, L. G. et al. NK cell transcripts and NK cells in kidney biopsies from patients with donor-specific antibodies: evidence for NK cell involvement in antibody-mediated rejection. Am. J. Transplant. 10, 1812–1822 (2010).

    Article  CAS  PubMed  Google Scholar 

  57. Smith, R. N. et al. Four stages and lack of stable accommodation in chronic alloantibody-mediated renal allograft rejection in Cynomolgus monkeys. Am. J. Transplant. 8, 1662–1672 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Nickeleit, V., Zeiler, M., Gudat, F., Thiel, G. & Mihatsch, M. J. Detection of the complement degradation product C4d in renal allografts: diagnostic and therapeutic implications. J. Am. Soc. Nephrol. 13, 242–251 (2002).

    CAS  PubMed  Google Scholar 

  59. Farris, A. B. et al. Acute renal endothelial injury during marrow recovery in a cohort of combined kidney and bone marrow allografts. Am. J. Transplant. 11, 1464–1477 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Nankivell, B. J. et al. The natural history of chronic allograft nephropathy. N. Engl. J. Med. 349, 2326–2333 (2003).

    Article  CAS  PubMed  Google Scholar 

  61. Snanoudj, R. et al. Specificity of histological markers of long-term CNI nephrotoxicity in kidney transplant recipients under low-dose cyclosporine therapy. Am. J. Transplant. 11, 2635–2646 (2011).

    Article  CAS  PubMed  Google Scholar 

  62. Chapman, J. R. Chronic calcineurin inhibitor nephrotoxicity—lest we forget. Am. J. Transplant. 11, 693–697 (2011).

    Article  CAS  PubMed  Google Scholar 

  63. Sis, B. et al. Reproducibility studies on arteriolar hyaline thickening scoring in calcineurin inhibitor-treated renal allograft recipients. Am. J. Transplant. 6, 1444–1450 (2006).

    Article  CAS  PubMed  Google Scholar 

  64. Meehan, S. M. et al. De novo collapsing glomerulopathy in renal allografts. Transplantation 65, 1192–1197 (1998).

    Article  CAS  PubMed  Google Scholar 

  65. Dogan, E., Ghanta, M. & Tanriover, B. Collapsing glomerulopathy in a renal transplant recipient: potential molecular mechanisms. Ann. Transplant. 16, 113–116 (2011).

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  67. Rubin, M. F. Hypertension following kidney transplantation. Adv. Chronic Kidney Dis. 18, 17–22 (2011).

    Article  PubMed  Google Scholar 

  68. Hurst, F. P. et al. Incidence, predictors and outcomes of transplant renal artery stenosis after kidney transplantation: analysis of USRDS. Am. J. Nephrol. 30, 459–467 (2009).

    Article  CAS  PubMed  Google Scholar 

  69. Mengel, M. et al. Incidence of C4d stain in protocol biopsies from renal allografts: results from a multicenter trial. Am. J. Transplant. 5, 1050–1056 (2005).

    Article  PubMed  Google Scholar 

  70. Haas, M. et al. C4d and C3d staining in biopsies of ABO- and HLA-incompatible renal allografts: correlation with histologic findings. Am. J. Transplant. 6, 1829–1840 (2006).

    Article  CAS  PubMed  Google Scholar 

  71. Kraus, E. S. et al. Subclinical rejection in stable positive crossmatch kidney transplant patients: incidence and correlations. Am. J. Transplant. 9, 1826–1834 (2009).

    Article  CAS  PubMed  Google Scholar 

  72. Khamash, H. A. et al. Polyomavirus-associated nephropathy risk in kidney transplants: the influence of recipient age and donor gender. Kidney Int. 71, 1302–1309 (2007).

    Article  CAS  PubMed  Google Scholar 

  73. Seron, D. & Moreso, F. Protocol biopsies in renal transplantation: prognostic value of structural monitoring. Kidney Int. 72, 690–697 (2007).

    Article  CAS  PubMed  Google Scholar 

  74. Mengel, M. et al. Protocol biopsies in renal transplantation: insights into patient management and pathogenesis. Am. J. Transplant. 7, 512–517 (2007).

    Article  CAS  PubMed  Google Scholar 

  75. Lipman, M. L., Stevens, A. C. & Strom, T. B. Cytotoxic T lymphocyte (CTL) and immunosuppressive cytokine gene expression in human renal allograft biopsies. J. Am. Soc. Nephrol. 3, 867–872 (1992).

    Google Scholar 

  76. Nast, C. C. et al. γ-Interferon gene expression in human renal allograft fine-needle aspirates. Transplantation 57, 498–502 (1994).

    Article  CAS  PubMed  Google Scholar 

  77. Eikmans, M. et al. High transforming growth factor-β and extracellular matrix mRNA response in renal allografts during early acute rejection is associated with absence of chronic rejection. Transplantation 73, 573–579 (2002).

    Article  CAS  PubMed  Google Scholar 

  78. Sarwal, M. et al. Molecular heterogeneity in acute renal allograft rejection identified by DNA microarray profiling. N. Engl. J. Med. 349, 125–138 (2003).

    Article  CAS  PubMed  Google Scholar 

  79. Hueso, M. et al. Intragraft expression of the IL-10 gene is up-regulated in renal protocol biopsies with early interstitial fibrosis, tubular atrophy, and subclinical rejection. Am. J. Pathol. 176, 1696–1704 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Einecke, G. et al. Expression of B cell and immunoglobulin transcripts is a feature of inflammation in late allografts. Am. J. Transplant. 8, 1434–1443 (2008).

    Article  CAS  PubMed  Google Scholar 

  81. Ashton-Chess, J. et al. Regulatory, effector, and cytotoxic T cell profiles in long-term kidney transplant patients. J. Am. Soc. Nephrol. 20, 1113–1122 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  82. Homs, S. et al. Predominant TH1 and cytotoxic phenotype in biopsies from renal transplant recipients with transplant glomerulopathy. Am. J. Transplant. 9, 1230–1236 (2009).

    Article  CAS  PubMed  Google Scholar 

  83. Halloran, P. F. et al. The molecular phenotype of kidney transplants. Am. J. Transplant. 10, 2215–2222 (2010).

    Article  CAS  PubMed  Google Scholar 

  84. Isse, K. et al. Adding value to liver (and allograft) biopsy evaluation using a combination of multiplex quantum dot immunostaining, high-resolution whole-slide digital imaging, and automated image analysis. Clin. Liver Dis. 14, 669–685 (2010).

    Article  PubMed  Google Scholar 

  85. Park, W. D., Griffin, M. D., Cornell, L. D., Cosio, F. G. & Stegall, M. D. Fibrosis with inflammation at one year predicts transplant functional decline. J. Am. Soc. Nephrol. 21, 1987–1997 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  86. Mueller, T. F. et al. Microarray analysis of rejection in human kidney transplants using pathogenesis-based transcript sets. Am. J. Transplant. 7, 2712–2722 (2007).

    Article  CAS  PubMed  Google Scholar 

  87. Mengel, M., Sis, B. & Halloran, P. F. SWOT analysis of Banff: strengths, weaknesses, opportunities and threats of the international Banff consensus process and classification system for renal allograft pathology. Am. J. Transplant. 7, 2221–2226 (2007).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  89. Matas, A. et al. Histopathologic clusters differentiate subgroups within the nonspecific diagnoses of CAN or CR: preliminary data from the DeKAF study. Am. J. Transplant. 10, 315–323 (2010).

    Article  CAS  PubMed  Google Scholar 

  90. Servais, A. et al. Interstitial fibrosis quantification in renal transplant recipients randomized to continue cyclosporine or convert to sirolimus. Am. J. Transplant. 9, 2552–2560 (2009).

    Article  CAS  PubMed  Google Scholar 

  91. Farris, A. B. et al. Morphometric and visual evaluation of fibrosis in renal biopsies. J. Am. Soc. Nephrol. 22, 176–186 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  92. Veronese, F. et al. Pathological and clinical correlates of FOXP3+ cells in renal allografts during acute rejection. Am. J. Transplant. 7, 914–922 (2007).

    Article  CAS  PubMed  Google Scholar 

  93. Bunnag, S. et al. FOXP3 expression in human kidney transplant biopsies is associated with rejection and time post transplant but not with favorable outcomes. Am. J. Transplant. 8, 1423–1433 (2008).

    Article  CAS  PubMed  Google Scholar 

  94. Yapici, U. et al. Intragraft FOXP3 protein or mRNA during acute renal allograft rejection correlates with inflammation, fibrosis, and poor renal outcome. Transplantation 87, 1377–1380 (2009).

    Article  CAS  PubMed  Google Scholar 

  95. Miyajima, M. et al. Early acceptance of renal allografts in mice is dependent on Foxp3+ cells. Am. J. Pathol. 178, 1635–1645 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Bestard, O. et al. Presence of FoxP3+ regulatory T cells predicts outcome of subclinical rejection of renal allografts. J. Am. Soc. Nephrol. 19, 2020–2026 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  97. Mansour, H. et al. Intragraft levels of Foxp3 mRNA predict progression in renal transplants with borderline change. J. Am. Soc. Nephrol. 19, 2277–2281 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Grimbert, P. et al. The regulatory/cytotoxic graft-infiltrating T cells differentiate renal allograft borderline change from acute rejection. Transplantation 83, 341–346 (2007).

    Article  CAS  PubMed  Google Scholar 

  99. Bestard, O. et al. Achieving donor-specific hyporesponsiveness is associated with FOXP3+ regulatory T cell recruitment in human renal allograft infiltrates. J. Immunol. 179, 4901–4909 (2007).

    Article  CAS  PubMed  Google Scholar 

  100. Muthukumar, T. et al. Messenger RNA for FOXP3 in the urine of renal-allograft recipients. N. Engl. J. Med. 353, 2342–2351 (2005).

    Article  CAS  PubMed  Google Scholar 

  101. Zhang, X. & Reed, E. F. Effect of antibodies on endothelium. Am. J. Transplant. 9, 2459–2465 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank the NIH and the Roche Organ Transplant Research Foundation for grant support and A. Bernard Collins, Martin Selig and Patricia Della Pelle for their outstanding technical contributions to biopsy analysis.

Author information

Authors and Affiliations

  1. Transplant Center, Massachusetts General Hospital, 55 Fruit Street, Boston, 02114, MA, USA

    Winfred W. Williams & Nina Tolkoff-Rubin

  2. Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, 02114, MA, USA

    Diana Taheri & Robert B. Colvin

Authors
  1. Winfred W. Williams
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Diana Taheri
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nina Tolkoff-Rubin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Robert B. Colvin
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

W. W. Williams, D. Taheri and R. B. Colvin researched the data for the article and wrote the manuscript. W. W. Williams, D. Taheri, N. Tolkoff-Rubin and R. B. Colvin contributed substantially to discussions of the article content and undertook review and/or editing of the manuscript before submission.

Corresponding author

Correspondence to Winfred W. Williams.

Ethics declarations

Competing interests

R. B. Colvin declares that he has acted as a consultant for Alexion, Amicus, Genzyme, GlaxoSmithKline and Novartis. The other authors declare no competing interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Williams, W., Taheri, D., Tolkoff-Rubin, N. et al. Clinical role of the renal transplant biopsy. Nat Rev Nephrol 8, 110–121 (2012). https://doi.org/10.1038/nrneph.2011.213

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrneph.2011.213

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research