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Cancer in kidney transplant recipients

Nature Reviews Nephrology volume 14, pages 508–520 (2018)Cite this article

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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.

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Fig. 1: Altered immune phenotype seen in kidney transplant recipients with cancer and potential mechanisms contributing to cancer.
Fig. 2: Risk categories for donor tumour transmission.
Fig. 3: Summary of cancer screening recommendations after kidney transplantation.

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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.

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Authors and 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

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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.

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Correspondence to Jeremy R. Chapman.

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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.

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Au, E., Wong, G. & Chapman, J.R. Cancer in kidney transplant recipients. Nat Rev Nephrol 14, 508–520 (2018). https://doi.org/10.1038/s41581-018-0022-6

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