Review Article | Published:

Cancer in kidney transplant recipients

Nature Reviews Nephrology (2018) | Download Citation

Abstract

Cancer is the second most common cause of mortality and morbidity in kidney transplant recipients after cardiovascular disease. Kidney transplant recipients have at least a twofold higher risk of developing or dying from cancer than the general population. The increased risk of de novo and recurrent cancer in transplant recipients is multifactorial and attributed to oncogenic viruses, immunosuppression and altered T cell immunity. Transplant candidates and potential donors should be screened for cancer as part of the assessment process. For potential recipients with a prior history of cancer, waiting periods of 2–5 years after remission — largely depending on the cancer type and stage of initial cancer diagnosis — are recommended. Post-transplantation cancer screening needs to be tailored to the individual patient, considering the cancer risk of the individual, comorbidities, overall prognosis and the screening preferences of the patient. In kidney transplant recipients diagnosed with cancer, treatment includes conventional approaches, such as radiotherapy and chemotherapy, together with consideration of altering immunosuppression. As the benefits of transplantation compared with dialysis in potential transplant candidates with a history of cancer have not been assessed, current clinical practice relies on evidence from observational studies and registry analyses.

Key points

  • Kidney transplant recipients have a twofold to fourfold higher risk of cancer and cancer-related death than age-matched and gender-matched individuals in the general population.

  • The increased risk of cancer in kidney transplant recipients is multifactorial and attributed to oncogenic viruses, immunosuppression and altered T cell immunity.

  • For potential kidney transplant recipients with a history of cancer, a waiting period of 2–5 years after cancer treatment is generally recommended before kidney transplantation.

  • Owing to a lack of direct evidence, general cancer screening in kidney transplant recipients is not recommended; instead, cancer screening should be tailored to patients individually, taking into account their comorbidities, individual risks of cancer, overall prognosis and preferences towards cancer screening.

  • In transplant recipients who develop cancer, treatment strategies include the careful reduction of immunosuppression and the use of standard cancer treatments, with consideration given to drug dosing, drug–drug interactions and the potential impact of chemotherapeutic agents on graft function.

  • Subscribe to Nature Reviews Nephrology for full access:

    $199

    Subscribe

Additional access options:

Already a subscriber?  Log in  now or  Register  for online access.

Additional information

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

NOTIFY library: http://www.notifylibrary.org/

References

  1. 1.

    Cheung, C. Y. et al. Malignancies after kidney transplantation: Hong Kong renal registry. Am. J. Transplant 12, 3039–3046 (2012).

  2. 2.

    Collett, D., Mumford, L., Banner, N. R., Neuberger, J. & Watson, C. Comparison of the incidence of malignancy in recipients of different types of organ: a UK Registry audit. Am. J. Transplant 10, 1889–1896 (2010).

  3. 3.

    Engels, E. A. et al. Spectrum of cancer risk among U.S. solid organ transplant recipients. JAMA 306, 1891–1901 (2011).

  4. 4.

    Krynitz, B. et al. Risk of skin cancer and other malignancies in kidney, liver, heart and lung transplant recipients 1970 to 2008 — a Swedish population-based study. Int. J. Cancer 132, 1429–1438 (2013).

  5. 5.

    Kyllonen, L., Salmela, K. & Pukkala, E. Cancer incidence in a kidney-transplanted population. Transpl. Int. 13 (Suppl. 1), S394–S398 (2000).

  6. 6.

    Li, W. H. et al. Malignancies after renal transplantation in Taiwan: a nationwide population-based study. Nephrol. Dial. Transplant. 27, 833–839 (2012).

  7. 7.

    Piselli, P. et al. Risk of de novo cancers after transplantation: results from a cohort of 7217 kidney transplant recipients, Italy 1997–2009. Eur. J. Cancer 49, 336–344 (2013).

  8. 8.

    Stewart, J. H. et al. The pattern of excess cancer in dialysis and transplantation. Nephrol. Dial. Transplant. 24, 3225–3231 (2009).

  9. 9.

    Tessari, G. et al. Incidence of primary and second cancers in renal transplant recipients: a multicenter cohort study. Am. J. Transplant. 13, 214–221 (2013).

  10. 10.

    Vajdic, C. M. et al. Cancer incidence before and after kidney transplantation. JAMA 296, 2823–2831 (2006).

  11. 11.

    Villeneuve, P. J. et al. Cancer incidence among Canadian kidney transplant recipients. Am. J. Transplant. 7, 941–948 (2007).

  12. 12.

    Yanik, E. L., Clarke, C. A., Snyder, J. J., Pfeiffer, R. M. & Engels, E. A. Variation in cancer incidence among patients with ESRD during kidney function and nonfunction intervals. J. Am. Soc. Nephrol. 27, 1495–1504 (2016).

  13. 13.

    Chapman, J. R. & Webster, A. C. in ANZDATA Registry 2004 Report 99–103 (Australia and New Zealand Dialysis and Transplant Registry, Adelaide, South Australia, Australia, 2004).

  14. 14.

    Shiels, M. S. et al. Cancer stage at diagnosis in HIV-infected people and transplant recipients. Cancer 121, 2063–2071 (2015).

  15. 15.

    van de Wetering, J., Roodnat, J. I., Hemke, A. C., Hoitsma, A. J. & Weimar, W. Patient survival after the diagnosis of cancer in renal transplant recipients: a nested case-control study. Transplantation 90, 1542–1546 (2010).

  16. 16.

    Miao, Y. et al. De novo cancers arising in organ transplant recipients are associated with adverse outcomes compared with the general population. Transplantation 87, 1347–1359 (2009).

  17. 17.

    Acuna, S. A. et al. Cancer mortality among recipients of solid-organ transplantation in ontario, canada. JAMA Oncol. 2, 463–469 (2016).

  18. 18.

    Farrugia, D. et al. Malignancy-related mortality following kidney transplantation is common. Kidney Int. 85, 1395–1403 (2014).

  19. 19.

    Kiberd, B. A., Rose, C. & Gill, J. S. Cancer mortality in kidney transplantation. Am. J. Transplant. 9, 1868–1875 (2009).

  20. 20.

    Vogelzang, J. L. et al. Mortality from infections and malignancies in patients treated with renal replacement therapy: data from the ERA-EDTA registry. Nephrol. Dial. Transplant. 30, 1028–1037 (2015).

  21. 21.

    Wong, G. et al. Time on dialysis and cancer risk after kidney transplantation. Transplantation 95, 114–121 (2013).

  22. 22.

    Webster, A. C., Craig, J. C., Simpson, J. M., Jones, M. P. & Chapman, J. R. Identifying high risk groups and quantifying absolute risk of cancer after kidney transplantation: a cohort study of 15,183 recipients. Am. J. Transplant. 7, 2140–2151 (2007).

  23. 23.

    Kasiske, B. L., Snyder, J. J., Gilbertson, D. T. & Wang, C. Cancer after kidney transplantation in the United States. Am. J. Transplant 4, 905–913 (2004).

  24. 24.

    Navarro, M. D. et al. Cancer incidence and survival in kidney transplant patients. Transplant. Proc. 40, 2936–2940 (2008).

  25. 25.

    Vigneri, P., Frasca, F., Sciacca, L., Pandini, G. & Vigneri, R. Diabetes and cancer. Endocr. Relat. Cancer 16, 1103–1123 (2009).

  26. 26.

    Yu, T. M. et al. Risk of cancer in patients with polycystic kidney disease: a propensity-score matched analysis of a nationwide, population-based cohort study. Lancet Oncol. 17, 1419–1425 (2016).

  27. 27.

    Wetmore, J. B. et al. Polycystic kidney disease and cancer after renal transplantation. J. Am. Soc. Nephrol. 25, 2335–2341 (2014).

  28. 28.

    Orskov, B., Sørensen, V. R., Feldt-Rasmussen, B. & Strandgaard, S. Changes in causes of death and risk of cancer in Danish patients with autosomal dominant polycystic kidney disease and end-stage renal disease. Nephrol. Dial. Transplant. 27, 1607–1613 (2012).

  29. 29.

    Schwarz, A., Vatandaslar, S., Merkel, S. & Haller, H. Renal cell carcinoma in transplant recipients with acquired cystic kidney disease. Clin. J. Am. Soc. Nephrol. 2, 750–756 (2007).

  30. 30.

    Kliem, V. et al. High mortality from urothelial carcinoma despite regular tumor screening in patients with analgesic nephropathy after renal transplantation. Transpl. Int. 9, 231–235 (1996).

  31. 31.

    Nortier, J. L. et al. Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi). N. Engl. J. Med. 342, 1686–1692 (2000).

  32. 32.

    Kanaan, N. et al. Long-term outcome of kidney recipients transplanted for aristolochic acid nephropathy. Transplantation 100, 416–421 (2016).

  33. 33.

    Dantal, J. et al. Effect of long-term immunosuppression in kidney-graft recipients on cancer incidence: randomised comparison of two cyclosporin regimens. Lancet 351, 623–628 (1998).

  34. 34.

    van Leeuwen, M. T. et al. Effect of reduced immunosuppression after kidney transplant failure on risk of cancer: population based retrospective cohort study. BMJ 340, c570 (2010).

  35. 35.

    Lim, W. H. et al. Acute rejection, T cell-depleting antibodies, and cancer after transplantation. Transplantation 97, 817–825 (2014).

  36. 36.

    Opelz, G., Naujokat, C., Daniel, V., Terness, P. & Dohler, B. Disassociation between risk of graft loss and risk of non-Hodgkin lymphoma with induction agents in renal transplant recipients. Transplantation 81, 1227–1233 (2006).

  37. 37.

    Bustami, R. T. et al. Immunosuppression and the risk of post-transplant malignancy among cadaveric first kidney transplant recipients. Am. J. Transplant. 4, 87–93 (2004).

  38. 38.

    Cherikh, W. S. et al. Association of the type of induction immunosuppression with posttransplant lymphoproliferative disorder, graft survival, and patient survival after primary kidney transplantation. Transplantation 76, 1289–1293 (2003).

  39. 39.

    Hall, E. C., Engels, E. A., Pfeiffer, R. M. & Segev, D. L. Association of antibody induction immunosuppression with cancer after kidney transplantation. Transplantation 99, 1051–1057 (2015).

  40. 40.

    Lim, W. et al. Effect of interleukin-2 receptor antibody therapy on acute rejection risk and severity, long-term renal function, infection and malignancy-related mortality in renal transplant recipients. Transpl. Int. 23, 1207–1215 (2010).

  41. 41.

    Webster, A. C. et al. Interleukin 2 receptor antagonists for kidney transplant recipients. Cochrane Database Syst. Rev. 1, CD003897 (2010).

  42. 42.

    Francis, A., Johnson, D. W., Teixeira-Pinto, A., Craig, J. C. & Wong, G. Incidence and predictors of post-transplant lymphoproliferative disease after kidney transplantation during adulthood and childhood: a registry study. Nephrol. Dial. Transplant. https://doi.org/10.1093/ndt/gfx356 (2018).

  43. 43.

    Knoll, G. A. et al. Effect of sirolimus on malignancy and survival after kidney transplantation: systematic review and meta-analysis of individual patient data. BMJ 349, g6679 (2014).

  44. 44.

    Lim, W. H. et al. A systematic review of conversion from calcineurin inhibitor to mammalian target of rapamycin inhibitors for maintenance immunosuppression in kidney transplant recipients. Am. J. Transplant. 14, 2106–2119 (2014).

  45. 45.

    Yanik, E. L., Siddiqui, K. & Engels, E. A. Sirolimus effects on cancer incidence after kidney transplantation: a meta-analysis. Cancer Med. 4, 1448–1459 (2015).

  46. 46.

    Campbell, S. B., Walker, R., Tai, S. S., Jiang, Q. & Russ, G. R. Randomized controlled trial of sirolimus for renal transplant recipients at high risk for nonmelanoma skin cancer. Am. J. Transplant. 12, 1146–1156 (2012).

  47. 47.

    Euvrard, S. et al. Sirolimus and secondary skin-cancer prevention in kidney transplantation. N. Engl. J. Med. 367, 329–339 (2012).

  48. 48.

    Hoogendijk-van den Akker, J. M. et al. Two-year randomized controlled prospective trial converting treatment of stable renal transplant recipients with cutaneous invasive squamous cell carcinomas to sirolimus. J. Clin. Oncol. 31, 1317–1323 (2013).

  49. 49.

    Lim, W. H., Chapman, J. R. & Wong, G. Peak panel reactive antibody, cancer, graft, and patient outcomes in kidney transplant recipients. Transplantation 99, 1043–1050 (2015).

  50. 50.

    Hussain, S. K. et al. HLA and risk of diffuse large B cell lymphoma after solid organ transplantation. Transplantation 100, 2453–2460 (2016).

  51. 51.

    Lustberg, M. E. et al. Human leukocyte antigen type and posttransplant lymphoproliferative disorder. Transplantation 99, 1220–1225 (2015).

  52. 52.

    Ma, M. K. et al. The risk of cancer in recipients of living-donor, standard and expanded criteria deceased donor kidney transplants: a registry analysis. Transplantation 98, 1286–1293 (2014).

  53. 53.

    Desai, R. et al. Impact of cytomegalovirus on long-term mortality and cancer risk after organ transplantation. Transplantation 99, 1989–1994 (2015).

  54. 54.

    Alexiev, B. A., Randhawa, P., Drachenberg, C. B. & Papadimitriou, J. C. BK virus-associated urinary bladder carcinoma in transplant recipients: productive or nonproductive polyomavirus infections in tumor cells? — reply. Hum. Pathol. 44, 2871–2872 (2013).

  55. 55.

    Yan, L., Salama, M. E., Lanciault, C., Matsumura, L. & Troxell, M. L. Polyomavirus large T antigen is prevalent in urothelial carcinoma post-kidney transplant. Hum. Pathol. 48, 122–131 (2016).

  56. 56.

    Papadimitriou, J. C. et al. BK polyomavirus infection and renourinary tumorigenesis. Am. J. Transplant 16, 398–406 (2016).

  57. 57.

    Grulich, A. E., van Leeuwen, M. T., Falster, M. O. & Vajdic, C. M. Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Lancet 370, 59–67 (2007).

  58. 58.

    Piselli, P. et al. De novo malignancies after organ transplantation: focus on viral infections. Curr. Mol. Med. 13, 1217–1227 (2013).

  59. 59.

    Peraldi, M. N. et al. Natural killer lymphocytes are dysfunctional in kidney transplant recipients on diagnosis of cancer. Transplantation 99, 2422–2430 (2015).

  60. 60.

    Morteau, O. et al. Renal transplant immunosuppression impairs natural killer cell function in vitro and in vivo. PLoS ONE 5, e13294 (2010).

  61. 61.

    Bottomley, M. J., Harden, P. N. & Wood, K. J. CD8+ immunosenescence predicts post-transplant cutaneous squamous cell carcinoma in high-risk patients. J. Am. Soc. Nephrol. 27, 1505–1515 (2016).

  62. 62.

    Carroll, R. P. et al. Immune phenotype predicts risk for posttransplantation squamous cell carcinoma. J. Am. Soc. Nephrol. 21, 713–722 (2010).

  63. 63.

    Lin, W. X. et al. Foxp3+ T cells in peripheral blood of renal transplant recipients and clinical correlations. Nephrology 17, 415–422 (2012).

  64. 64.

    Whiteside, T. L. What are regulatory T cells (Treg) regulating in cancer and why? Semin. Cancer Biol. 22, 327–334 (2012).

  65. 65.

    Hope, C. M. et al. The immune phenotype may relate to cancer development in kidney transplant recipients. Kidney Int. 86, 175–183 (2014).

  66. 66.

    Hojo, M. et al. Cyclosporine induces cancer progression by a cell-autonomous mechanism. Nature 397, 530–534 (1999).

  67. 67.

    Basu, A. et al. Overexpression of vascular endothelial growth factor and the development of post-transplantation cancer. Cancer Res. 68, 5689–5698 (2008).

  68. 68.

    Guba, M., Graeb, C., Jauch, K.-W. & Geissler, E. Pro- and anti-cancer effects of immunosuppressive agent used in organ transplantation. Transplantation 77, 1777–1782 (2004).

  69. 69.

    Maluccio, M. et al. Tacrolimus enhances transforming growth factor-beta1 expression and promotes tumor progression. Transplantation 76, 597–602 (2003).

  70. 70.

    Engels, E. A. et al. Circulating TGF-β1 and VEGF and risk of cancer among liver transplant recipients. Cancer Med. 4, 1252–1257 (2015).

  71. 71.

    Herman, M. et al. Effect of cyclosporin A on DNA repair and cancer incidence in kidney transplant recipients. J. Lab. Clin. Med. 137, 14–20 (2001).

  72. 72.

    Datta, D. et al. Calcineurin inhibitors activate the proto-oncogene Ras and promote protumorigenic signals in renal cancer cells. Cancer Res. 69, 8902–8909 (2009).

  73. 73.

    Jiang, K. et al. Cyclosporine A inhibits breast cancer cell growth by downregulating the expression of pyruvate kinase subtype M2. Int. J. Mol. Med. 30, 302–308 (2012).

  74. 74.

    Kauffman, H. M. et al. Transplant tumor registry: donor related malignancies. Transplantation 74, 358–362 (2002).

  75. 75.

    Desai, R. et al. Cancer transmission from organ donors-unavoidable but low risk. Transplantation 94, 1200–1207 (2012).

  76. 76.

    Xiao, D. et al. Donor cancer transmission in kidney transplantation: a systematic review. Am. J. Transplant 13, 2645–2652 (2013).

  77. 77.

    The Notify Library. The NOTIFY Booklet: Vigilance and Surveillance (V&S) of Medical Products of Human Origin (MPHO) (2014).

  78. 78.

    Nalesnik, M. A. et al. Donor-transmitted malignancies in organ transplantation: assessment of clinical risk. Am. J. Transplant 11, 1140–1147 (2011).

  79. 79.

    European Directorate for the Quality of Medicines & HealthCare of the Council of Europe. Guide to the Quality and Safety of Organs for Transplantation (Council of Europe, Strasbourg, France, 2016).

  80. 80.

    Tong, A., Chapman, J. R., Wong, G., de Bruijn, J. & Craig, J. C. Screening and follow-up of living kidney donors: a systematic review of clinical practice guidelines. Transplantation 92, 962–972 (2011).

  81. 81.

    Brook, N. R., Gibbons, N., Johnson, D. W. & Nicol, D. L. Outcomes of transplants from patients with small renal tumours, live unrelated donors and dialysis wait-listed patients. Transpl. Int. 23, 476–483 (2010).

  82. 82.

    Nicol, D. & Fujita, S. Kidneys from patients with small renal tumours used for transplantation: outcomes and results. Curr. Opin. Urol. 21, 380–385 (2011).

  83. 83.

    Watson, C. J. E. et al. How safe is it to transplant organs from deceased donors with primary intracranial malignancy? An analysis of UK registry data. Am. J. Transplant 10, 1437–1444 (2010).

  84. 84.

    Chui, A. K. et al. Risk of tumor transmission in transplantation from donors with primary brain tumors: an Australian and New Zealand registry report. Transplant. Proc. 31, 1266–1267 (1999).

  85. 85.

    Kauffman, H. M., McBride, M. A., Cherikh, W. S., Spain, P. C. & Delmonico, F. L. Transplant tumor registry: donors with central nervous system tumors. Transplantation 73, 579–582 (2002).

  86. 86.

    Warrens, A. N. et al. Advising potential recipients on the use of organs from donors with primary central nervous system tumors. Transplantation 93, 348–353 (2012).

  87. 87.

    Desai, R. et al. Estimated risk of cancer transmission from organ donor to graft recipient in a national transplantation registry. Br. J. Surg. 101, 768–774 (2014).

  88. 88.

    Campbell, S. et al. KHA-CARI guideline: recipient assessment for transplantation. Nephrology 18, 455–462 (2013).

  89. 89.

    European Renal Best Practice Transplantation Guideline Development Group. ERBP guideline on the management and evaluation of the kidney donor and recipient. Nephrol. Dial. Transplant. 28 (Suppl. 2), ii1–ii71 (2013).

  90. 90.

    Kalble, T. et al. EAU guidelines on renal transplantation. Eur. Urol. 47, 156–166 (2005).

  91. 91.

    Kasiske, B. et al. The evaluation of the renal transplant candidates: clinical practice guidelines. Am. J. Transplant. 1, 1–95 (2001).

  92. 92.

    Knoll, G. et al. Canadian Society of Transplantation consensus guidelines on eligibility for kidney transplantation. CMAJ 173, 1181–1184 (2005).

  93. 93.

    Segall, L. et al. Criteria for and appropriateness of renal transplantation in elderly patients with end-stage renal disease: a literature review and position statement on behalf of the European Renal Association-European Dialysis and Transplant Association Descartes Working Group and European Renal Best Practice. Transplantation 100, e55–65 (2016).

  94. 94.

    Maisonneuve, P. et al. Cancer in patients on dialysis for end-stage renal disease: an international collaborative study. Lancet 354, 93–99 (1999).

  95. 95.

    AlAmeel, T., Bseiso, B., AlBugami, M. M., AlMomen, S. & Roth, L. S. Yield of screening colonoscopy in renal transplant candidates. Can. J. Gastroenterol. Hepatol. 29, 423–426 (2015).

  96. 96.

    Saumoy, M. et al. High prevalence of colon adenomas in end-stage kidney disease patients on hemodialysis undergoing renal transplant evaluation. Clin. Transplant. 30, 256–262 (2016).

  97. 97.

    Therrien, A., Giard, J. M., Hebert, M. J. & Bouin, M. Importance of pre-transplant colonoscopy in renal transplant recipients. J. Clin. Med. Res. 6, 414–421 (2014).

  98. 98.

    Vitiello, G. A. et al. Utility of prostate cancer screening in kidney transplant candidates. J. Am. Soc. Nephrol. 27, 2157–2163 (2016).

  99. 99.

    Chapman, J. R., Sheil, A. G. & Disney, A. P. Recurrence of cancer after renal transplantation. Transplant. Proc. 33, 1830–1831 (2001).

  100. 100.

    Viecelli, A. K. et al. Cancer-specific and all-cause mortality in kidney transplant recipients with and without previous cancer. Transplantation 99, 2586–2592 (2015).

  101. 101.

    Acuna, S. A. et al. Cancer recurrence after solid organ transplantation:a systematic review and meta-analysis. Transplant. Rev. 31, 240–248 (2017).

  102. 102.

    Brattstrom, C., Granath, F., Edgren, G., Smedby, K. E. & Wilczek, H. E. Overall and cause-specific mortality in transplant recipients with a pretransplantation cancer history. Transplantation 96, 297–305 (2013).

  103. 103.

    Acuna, S. A. et al. Outcomes of solid organ transplant recipients with preexisting malignancies in remission: a systematic review and meta-analysis. Transplantation 101, 471–481 (2017).

  104. 104.

    Dahle, D. O. et al. Association between pretransplant cancer and survival in kidney transplant recipients. Transplantation 101, 2599–2605 (2017).

  105. 105.

    Hellstrom, V., Lorant, T., Dohler, B., Tufveson, G. & Enblad, G. High posttransplant cancer incidence in renal transplanted patients with pretransplant cancer. Transplantation 101, 1295–1302 (2017).

  106. 106.

    Batabyal, P., Chapman, J. R., Wong, G., Craig, J. C. & Tong, A. Clinical practice guidelines on wait-listing for kidney transplantation: consistent and equitable? Transplantation 94, 703–713 (2012).

  107. 107.

    Penn, I. The effect of immunosuppression on pre-existing cancers. Transplantation 55, 742–747 (1993).

  108. 108.

    Mukhtar, R. A. et al. The novel application of genomic profiling assays to shorten inactive status for potential kidney transplant recipients with breast cancer. Am. J. Transplant 17, 292–295 (2017).

  109. 109.

    Lin, J. S. et al. Screening for colorectal cancer: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA 315, 2576–2594 (2016).

  110. 110.

    Nelson, H. D. et al. Effectiveness of breast cancer screening: systematic review and meta-analysis to update the 2009 U.S. Preventive Services Task Force recommendation. Ann. Intern. Med. 164, 244–255 (2016).

  111. 111.

    Acuna, S. A. et al. Cancer screening recommendations for solid organ transplant recipients: a systematic review of clinical practice guidelines. Am. J. Transplant. 17, 103–114 (2017).

  112. 112.

    Baker, R. J., Mark, P. B., Patel, R. K., Stevens, K. K. & Palmer, N. Renal association clinical practice guideline in post-operative care in the kidney transplant recipient. BMC Nephrol. 18, 174 (2017).

  113. 113.

    Collins, M. G. et al. Screening for colorectal cancer and advanced colorectal neoplasia in kidney transplant recipients: cross sectional prevalence and diagnostic accuracy study of faecal immunochemical testing for haemoglobin and colonoscopy. BMJ 345, e4657 (2012).

  114. 114.

    Sangthawan, P., Fox, J., Atkins, R. C. & Kerr, P. G. Increased incidence of benign breast disease in female renal transplant patients receiving cyclosporin. ANZ J. Surg. 72, 222–225 (2002).

  115. 115.

    Wong, G., Howard, K., Chapman, J. R. & Craig, J. C. Cost-effectiveness of breast cancer screening in women on dialysis. Am. J. Kidney Dis. 52, 916–929 (2008).

  116. 116.

    Wong, G., Howard, K., Craig, J. C. & Chapman, J. R. Cost-effectiveness of colorectal cancer screening in renal transplant recipients. Transplantation 85, 532–541 (2008).

  117. 117.

    Wong, G., Howard, K., Webster, A., Chapman, J. R. & Craig, J. C. The health and economic impact of cervical cancer screening and human papillomavirus vaccination in kidney transplant recipients. Transplantation 87, 1078–1091 (2009).

  118. 118.

    Wong, G., Howard, K., Webster, A. C., Chapman, J. R. & Craig, J. C. Screening for renal cancer in recipients of kidney transplants. Nephrol. Dial. Transplant. 26, 1729–1739 (2011).

  119. 119.

    Kiberd, B. A., Keough-Ryan, T. & Clase, C. M. Screening for prostate, breast and colorectal cancer in renal transplant recipients. Am. J. Transplant 3, 619–625 (2003).

  120. 120.

    Lim, E. J., Morgan, J. & Fielding, R. Cervical screening uptake in immunocompromised women in Waikato, New Zealand. Int. J. STD AIDS 21, 835–836 (2010).

  121. 121.

    Wong, G. et al. Patterns and predictors of screening for breast and cervical cancer in women with CKD. Clin. J. Am. Soc. Nephrol. 12, 95–104 (2016).

  122. 122.

    Williams, N. C. et al. Knowledge, beliefs and attitudes of kidney transplant recipients regarding their risk of cancer. Nephrology 17, 300–306 (2012).

  123. 123.

    Reshef, R. et al. Reduction of immunosuppression as initial therapy for posttransplantation lymphoproliferative disorder. Am. J. Transplant 11, 336–347 (2011).

  124. 124.

    Hope, C. M., Krige, A. J., Barratt, A. & Carroll, R. P. Reductions in immunosuppression after haematological or solid organ cancer diagnosis in kidney transplant recipients. Transpl. Int. 28, 1332–1335 (2015).

  125. 125.

    Guba, M. et al. Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor. Nat. Med. 8, 128–135 (2002).

  126. 126.

    Nichols, L. A., Adang, L. A. & Kedes, D. H. Rapamycin blocks production of KSHV/HHV8: insights into the anti-tumor activity of an immunosuppressant drug. PLoS ONE 6, e14535 (2011).

  127. 127.

    Basu, G., Mohapatra, A., Manipadam, M. T., Mani, S. E. & John, G. T. Leflunomide with low-dose everolimus for treatment of Kaposi’s sarcoma in a renal allograft recipient. Nephrol. Dial. Transplant. 26, 3412–3415 (2011).

  128. 128.

    Yaich, S. et al. Sirolimus for the treatment of Kaposi sarcoma after renal transplantation: a series of 10 cases. Transplant Proc. 44, 2824–2826 (2012).

  129. 129.

    Cullis, B. et al. Sirolimus-induced remission of posttransplantation lymphoproliferative disorder. Am. J. Kidney Dis. 47, e67–e72 (2006).

  130. 130.

    Boratynska, M., Watorek, E., Smolska, D., Patrzałek, D. & Klinger, M. Anticancer effect of sirolimus in renal allograft recipients with de novo malignancies. Transplant. Proc. 39, 2736–2739 (2007).

  131. 131.

    Alhamad, T., Venkatachalam, K., Linette, G. P. & Brennan, D. C. Checkpoint inhibitors in kidney transplant recipients and the potential risk of rejection. Am. J. Transplant. 16, 1332–1333 (2016).

  132. 132.

    Jose, A. et al. Renal allograft failure after ipilimumab therapy for metastatic melanoma: a case report and review of the literature. Transplant. Proc. 48, 3137–3141 (2016).

  133. 133.

    Lipson, E. J. et al. Tumor regression and allograft rejection after administration of anti-PD-1. N. Engl. J. Med. 374, 896–898 (2016).

  134. 134.

    Ong, M. et al. Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. J. Immunother. Cancer 4, 64 (2016).

  135. 135.

    Spain, L. et al. Acute renal allograft rejection after immune checkpoint inhibitor therapy for metastatic melanoma. Ann. Oncol. 27, 1135–1137 (2016).

  136. 136.

    Barnett, R., Barta, V. S. & Jhaveri, K. D. Preserved renal-allograft function and the PD-1 pathway inhibitor nivolumab. N. Engl. J. Med. 376, 191–192 (2017).

  137. 137.

    Lipson, E. J., Bodell, M. A., Kraus, E. S. & Sharfman, W. H. Successful administration of ipilimumab to two kidney transplantation patients with metastatic melanoma. J. Clin. Oncol. 32, e69–e71 (2014).

  138. 138.

    Opelz, G. & Dohler, B. Influence of current and previous smoking on cancer and mortality after kidney transplantation. Transplantation 100, 227–232 (2016).

  139. 139.

    Ingvar, A. et al. Immunosuppressive treatment after solid organ transplantation and risk of post-transplant cutaneous squamous cell carcinoma. Nephrol. Dial. Transplant. 25, 2764–2771 (2010).

Download references

Reviewer information

Nature Reviews Nephrology thanks M. Gallieni, E. Geissler and the other anonymous reviewer(s) for their contribution to the peer review of this work.

Author information

Affiliations

  1. Centre for Transplant and Renal Research, Westmead Hospital, Westmead, New South Wales, Australia

    • Eric Au
    • , Germaine Wong
    •  & Jeremy R. Chapman
  2. Sydney School of Public Health, University of Sydney, Sydney, New South Wales, Australia

    • Germaine Wong

Authors

  1. Search for Eric Au in:

  2. Search for Germaine Wong in:

  3. Search for Jeremy R. Chapman in:

Contributions

E.A. and G.W. researched data for the article. All authors substantially co ntributed to the discussion of the content and wrote, drafted and edited the manuscript before submission.

Competing interests

The authors declare no competing interests.

Corresponding author

Correspondence to Jeremy R. Chapman.

Supplementary information

Glossary

Solid organ cancers

All cancers except soft tissue cancers and skin cancers such as non-melanoma skin cancer and melanoma.

Post-transplant lymphoproliferative disorder

(PTLD). Cancers due to abnormal cell proliferation in lymphoid tissue, which can occur after transplantation.

Standardized mortality ratio

(SMR). A ratio of the mortality of a population of interest, such as kidney transplant recipients, to the mortality of the general population, matched (standardized) by age and gender. This methodology allows for the comparison of the mortality of groups with different age and gender distributions with that of the general population.

Aristolochic acid

A group of compounds found in plants and traditional herbal medicines that are associated with the development of kidney failure as well as cancers of the bladder and urinary tract.

Cyclophosphamide

A chemotherapy agent that is used for the treatment of certain diseases, including some types of glomerulonephritis and cancer. The compound has been associated with the development of urothelial carcinoma.

Induction therapy

A short course of intense immunosuppressive therapy given at the start of transplantation to prevent acute rejection.

Panel reactive antibody

(PRA). An immunological test performed in potential transplant recipients to determine the presence of antibodies against a panel of possible donors. Results are presented on a scale of 0–99%, with a higher number indicating antibodies that react to a greater percentage of donors in the panel.

HLA-DR mismatches

Human leukocyte antigens, such as HLA-DR, are specific proteins on the surface of cells. A difference or mismatch of these antigens (HLA mismatch) between potential transplant donors and recipients can increase the risk of rejection.

Expanded criteria donor

A deceased donor who was aged ≥60 years or who was aged 50–59 with two of three factors: history of hypertension, elevated creatinine at time of death (>1.5 mg/dl) or suffered a cerebrovascular accident causing death.

Immunosenescent T cells

T cells that are functionally exhausted with impaired ability to proliferate and produce cytokines. This phenotype can occur through DNA damage (cellular senescence) or through repeated antigen stimulation and T cell replication (replicative senescence).

Backtable resection

Resection (of tumour or other part of the transplant organ) that occurs in the operating theatre but away from the recipient and before transplantation of the organ into the recipient.

Benign breast disease

A term for non-malignant diseases of the breast that can be detected on mammography, such as fibroadenoma and fibrocystic disease.

About this article

Publication history

Published

DOI

https://doi.org/10.1038/s41581-018-0022-6

Rights and permissions

To obtain permission to re-use content from this article visit RightsLink.