Malignancies after kidney transplantation: results of a 34-year population-based study

BACKGROUND. Cancer is the second most common cause of mortality and morbidity in kidney transplant recipients (KTRs) after cardiovascular diseases (CVDs). KTRs have at least twice the risk of developing cancer or dying from it compared to the general population. THE AIM: to calculate the standardized incidence ratio (SIR) and mortality ratio (SMR) of malignancies in KTRs registered at Municipal Clinical Hospital № 52 of the Moscow Healthcare Department and to determine independent risk factors for MN. PATIENTS AND METHODS. From January 1, 1989 to December 31, 2023, we followed 2146 KTRs registered at Municipal Clinical Hospital №52 of the Moscow Healthcare Department, in whom 14.4 % (n=310) MN were detected. In the malignancies group, the most common were non-melanoma skin cancer (NMSC) 30.3 % (n=91) and kidney cancer 11.3 % (n=41), 37.7 % (n=117) of patients died, of which 46.2 % (n=54) died directly from this cause. RESULTS. In kidney transplant recipients, the overall risk of malignancies was approximately three times higher than in the Russian population (SIR 2.85, 95 % CI: 2.4–3.2, P<0.05). The highest incidence was observed for kidney cancer SIR 5.8 (95 % CI: 4.0–7.5, P<0.05), non-melanoma skin cancer (NMSC) SIR 5.8 (95 % CI: 4.6–6.9, P<0.05), melanoma SIR 3.99 (95 % CI: 3.5–4.3, P<0.05), cervical cancer SIR 3.0 (95 % CI: 1.5–4.4, P<0.05), thyroid cancer SIR 2.1 (95 % CI: 1.4–2.9, P<0.05) and chronic lymphocytic leukemia (CLL, ICD codes: C91.1–9) SIR 10.3 (95 % CI: 4.5–16.0, P<0.05). Mortality from all types of malignancies after kidney transplantation slightly exceeded the general population mortality in the Russian Federation (SMR 1.3, 95 % CI: 1.1–1.4, P<0.05). The highest mortality after transplantation was from NMSC SMR 51.4 (95 % CI: 25.3–77.4, P<0.05) and melanoma SMR 8.6 (95 % CI: 2.5–14.6, P<0.05). CONCLUSIONS. The overall incidence of malignancies after kidney transplantation in patients registered at Municipal Clinical Hospital №52 of the Moscow Healthcare Department in 1989–2023 is almost 3 times higher than the general population incidence in the Russian Federation (overall SIR = 2.85 (95 % CI: 2.4–3.2, P<0.05). Mortality from malignancies (overall SMR = 1.3 (95 % CI: 1.1–1.4, P<0.05)) is slightly higher than the general population incidence. A possible reason for the almost twofold difference between the incidence and mortality from malignancies in the Russian Federation may be the high risk of competing causes of mortality in KTRs, especially CVDs.

1. Au E, Wong G, Chapman JR. Cancer in kidney transplant recipients. Nat Rev Nephrol 2018;14:508–520. doi: 10.1038/s41581-018-0022-6

2. Wong G, Hayen A, Chapman JR et al. Association of CKD and cancer risk in older people. J Am Soc Nephrol 20:1341–1350. doi: 10.1681/ASN.2008090998

3. Vajdic CM, McDonald SP, McCredie MR et al. Cancer incidence before and after kidney transplantation JAMA 2006;296:2823–2831. doi: 10.1001/jama.296.23.2823

4. Al-Adra D, Al-Qaoud T, Fowler K, Wong G. De Novo Malignancies after Kidney Transplantation Clin J Am Soc Nephrol 2022;17:434–443. doi: 10.2215/CJN.14570920

5. Kasiske BL, Snyder JJ, Gilbertson DT et al. Cancer after kidney transplantation in the United States. Am J Transplant 2004;4: 905–913. doi: 10.1111/j.1600-6143.2004.00450.x

6. Chapman JR, Webster AC, Wong G. Cancer in the Transplant Recipient. Cold Spring Harb Perspect Med 2013;3(7):a015677. doi: 10.1101/cshperspect.a015677

7. Massicotte-Azarniouch D, Noel JA, Knoll GA. Epidemiology of Cancer in Kidney Transplant Recipients. Seminars in Nephrology 2024;44 (1): 151494. doi: 10.1016/j.semnephrol.2024.151494

8. Kaprin AD, Starinsky VV, Shakhzadova AO. Malignancies in Russia in 2020 (incidence and mortality). Moscow 2021;35–43, 149–158 (In Russ.) https://oncology-association.ru/wp-content/uploads/2021/11/zis-2020elektronnaya-versiya.pdf

9. Henry KA, Sherman R, Roche LM. Colorectal cancer stage at diagnosis and area socioeconomic characteristics in New Jersey. Health Place 2009 Jun;15(2):505–513. doi: 10.1016/j.healthplace.2008.09.003

10. Zweig MH, Campbell G. ROC Plots: A Fundamental Evaluation Tool in Clinical Medicine. Clinical Chemistry 1993; 39(4) https://loginom.ru/blog/logistic-regression-roc-auc

11. Rea L, Parker R. Designing and conducting research. San Francisco: Jossey-Bass 2014

12. Petrov VI, Nedogoda SV. Evidence-based medicine. Geotar-Media, M., 2012, 12–45 (In Russ.)

13. Blosser CD, Haber G, Engels EA. Changes in cancer incidence and outcomes among kidney transplant recipients in the United States over a thirty-year period. Kidney Int 2021; 99: 1430–1438. doi: 10.1016/j.kint.2020.10.018

14. Wang Y, Lan GB, Peng FH. Cancer risks in recipients of renal transplants: a meta-analysis of cohort studies. Oncotarget 2018;9:15375–15385. doi: 10.18632/oncotarget.23841

15. Sprangers B, Riella LV, Dierickx D. Posttransplant Lymphoproliferative Disorder Following Kidney Transplantation: A Review. Am J Kidney Dis 2021; 78(2):272–281. doi: 10.1053/j.ajkd.2021.01.015

16. Lee M, Abousaud A, Harkins RA et al. Important Considerations in the Diagnosis and Management of Post-transplant Lymphoproliferative Disorder. Curr Oncol Rep 2023; 25(8):883–895. doi: 10.1007/s11912-023-01418-0

17. Dierickx D, De Rycke A, Vandenberghe P et al. Recipientderived chronic lymphocytic leukaemia diagnosed shortly after kidney transplantation on protocol biopsy. Nephrology Dialysis Transplantation 2009; 24 (12):3886–3890. doi: 10.1093/ndt/gfp444

18. Abbas F, El Kossi M, Shaheen IS et al. Post-transplantation lymphoproliferative disorders: Current concepts and future therapeutic approaches. World J Transplant 2020;10(2):29–46. doi: 10.5500/wjt.v10.i2.29

19. Kiberd BA, Rose C, Gill JS. Cancer Mortality in Kidney Transplantation. Am J Transplant 2009; 9 (8): 1868–1875. doi: 10.1111/j.1600-6143.2009.02728.x

20. Birdwell KA, Park M. Post-Transplant Cardiovascular Disease. CJASN 2021; 16 (12): 1878–1889. doi: 10.2215/CJN.00520121

21. Novikova MS, Minushkina LO, Kotenko ON et al. Mortality in kidney transplant recipients: a systematic review and meta-analysis of cohorts and clinical registries. Clinical Nephrology 2023; 1:5–12. (In Russ.) doi: 10.18565/nephrology.2023.1.5-12

22. Alcala K, Mariosa D, Smith-Byrne K et al. The relationship between blood pressure and risk of renal cell carcinoma. Int J Epidemiol 2022; 51(4):1317–1327. doi: 10.1093/ije/dyac042

23. Kim CS, Choi HS, Bae EH et al. Association of hypertension with the risk of kidney cancer: a nationwide population-based cohort study. Nephrology Dialysis Transplantation 2019;34(1): gfz103.SP050. doi: 10.1093/ndt/gfz103.SP050

24. Loureno J, Serrano A, Poveda V et al. Male gender and hypertension are independent variables associated with kidney cancer in Europe: results from the share study. Nephrology Dialysis Transplantation 2016;31(1):i102. doi: 10.1093/ndt/gfw157.10

25. Karami S, Yanik EL, Moore LE et al. Risk of Renal Cell Carcinoma among Kidney Transplant Recipients in the United States. Am J Transplant 2016;16(12):3479–3489. doi: 10.1111/ajt.13862