Langenbeck's Archives of Surgery

, Volume 403, Issue 5, pp 631–641 | Cite as

Renal cell cancer after kidney transplantation

  • Dennis Kleine-DöpkeEmail author
  • Matthias Oelke
  • Anke Schwarz
  • Ysabell Schwager
  • Frank Lehner
  • Jürgen Klempnauer
  • Harald Schrem



This study aims to identify modifiable risk factors for de novo renal cell carcinoma (RCC) after kidney transplantation in a matched-pair approach matching for unmodifiable factors.

Patients and methods

One thousand six hundred fifty-five adults who underwent kidney transplantation in the period 1 January 2000 to 31 December 2012 were analyzed. Patients with RCC after kidney transplantation were matched in a 1:2 ratio with those without RCC using the indication for transplantation, age at transplantation (± 10 years), recipient sex (male/female), number of received transplants, living organ donor transplantation (yes/no), and time of follow-up in days as matching criteria. The paired t test was used to compare continuous variables and the Cochran-Mantel-Haenszel test for categorical variables. Multivariable conditional logistic regression modeling was used to identify independent risk factors for RCC.


In matched-pair analysis, a total number of 26 incident cases with RCC after kidney transplantation could be matched. Post-transplant RCC was significantly associated with longer durations of pre-transplant hemodialysis (p = 0.007) and post-transplant immunosuppression with cyclosporine (p = 0.029) and/or mycophenolate mofetil (p = 0.020) and with larger proportions of post-transplant time on mycophenolate mofetil (p = 0.046) and/or prednisolone medication (p = 0.042). Multivariable conditional logistic regression modeling revealed a significant risk increasing multiplicative factor interaction between the duration of pre-transplant dialysis (years) and the time of prednisolone usage (percent/100). Cyclosporine A usage and mycophenolate mofetil usage were also revealed as independent, significant risk factors for RCC development.


Longer pre-transplant dialysis, cyclosporine-based protocols and/or intensified immunosuppression with additional mycophenolate mofetil, and larger proportions of time of prednisolone treatment during follow-up increase de novo RCC risk.


Renal cell cancer Renal transplantation Immunosuppression Hemodialysis Cyclosporine 


Sources of financial support

This work was supported by a grant from the German Federal Ministry of Education and Research (reference number 01EO1302).

Authors’ contributions

Study conception and design: Dennis Kleine-Döpke, Matthias Oelke, and Harald Schrem. Acquisition of data: Dennis Kleine-Döpke, Matthias Oelke, Ysabell Schwager, and Harald Schrem. Analysis and interpretation of data: Dennis Kleine-Döpke, Matthias Oelke, and Harald Schrem. Drafting of manuscript: Dennis Kleine-Döpke, Matthias Oelke, and Harald Schrem. Critical revision of manuscript: Dennis Kleine-Döpke, Matthias Oelke, Anke Schwarz, Ysabell Schwager, Frank Lehner, Jürgen Klempnauer, and Harald Schrem.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The Ethics Committee of Hannover Medical School approved this retrospective study (approval decision number 2706-2015).

Informed consent

Informed consent was obtained from all individual participants included in the study. Patients provided informed consent that their data may be used for scientific purposes at the time of hospital admission which is the general policy of our institution.

Supplementary material

423_2018_1694_MOESM1_ESM.pdf (218 kb)
ESM 1 (PDF 218 kb)


  1. 1.
    Kaatsch P, Spix C, Hentschel S et al (2013) Krebs in Deutschland 2009/2010. 9. Ausgabe. Robert Koch-Institut (Hrsg) und die Gesellschaft der epidemiologischen Krebsregister in Deutschland e.V. (Hrsg). Ruksaldruck, Berlin, ISBN 978-3-89606-221-5Google Scholar
  2. 2.
    Barnes B, Bertz J, Buttmann-Schweiger N et al (2016) Bericht zum Krebsgeschehen in Deutschland, Zentrum für Krebsregisterdaten im Robert Koch-Institut (Hrsg), Ruksaldruck, Berlin, ISBN: 978-3-89606-279-6.
  3. 3.
    Jonasch E, Gao J, Rathmell WK (2014) Renal cell carcinoma. BMJ 349:g4797CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Cohen HT, McGovern FJ (2005) Renal-cell carcinoma. N Engl J Med 353(23):2477–2490CrossRefPubMedGoogle Scholar
  5. 5.
    Ljungberg B, Albiges L, Bensalah K et al (2017) EAU Guidelines Renal Cell Carcinoma. Accessed 21 Dec 2017
  6. 6.
    Navai N, Wood CG (2012) Environmental and modifiable risk factors in renal cell carcinoma. Urol Oncol 30(2):220–224CrossRefPubMedGoogle Scholar
  7. 7.
    Macleod LC, Hotaling JM, Wright JL, Davenport MT, Gore JL, Harper J, White E (2013) Risk factors for renal cell carcinoma in the VITAL study. J Urol 190(5):1657–1661CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Chow WH, Gridley G, Fraumeni JF Jr, Järvholm B (2000) Obesity, hypertension, and the risk of kidney cancer in men. N Engl J Med 343(18):1305–1311CrossRefPubMedGoogle Scholar
  9. 9.
    Zhang GM, Zhu Y, Ye DW (2014) Metabolic syndrome and renal cell carcinoma. World J Surg Oncol 12:236CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Wang G, Hou J, Ma L, Xie J, Yin J, Xu D, Chang W, Tan X, Su T, Zhang H, Cao G (2012) Risk factor for clear cell renal cell carcinoma in Chinese population: a case-control study. Cancer Epidemiol 36(2):177–182CrossRefPubMedGoogle Scholar
  11. 11.
    Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M (2008) Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 371(9612):569–578CrossRefPubMedGoogle Scholar
  12. 12.
    Stewart JH, Buccianti G, Agodoa L, Gellert R, McCredie MR, Lowenfels AB, Disney AP, Wolfe RA, Boyle P, Maisonneuve P (2003) Cancers of the kidney and urinary tract in patients on dialysis for end-stage renal disease: analysis of data from the United States, Europe, and Australia and New Zealand. J Am Soc Nephrol 14(1):197–207CrossRefPubMedGoogle Scholar
  13. 13.
    Woldu SL, Weinberg AC, RoyChoudhury A, Chase H, Kalloo SD, McKiernan JM, DeCastro GJ (2014) Renal insufficiency is associated with an increased risk of papillary renal cell carcinoma histology. Int Urol Nephrol 46(11):2127–2132CrossRefPubMedGoogle Scholar
  14. 14.
    Otunctemur A, Ozbek E, Sahin S, Dursun M, Besiroglu H, Koklu I, Erkoc M, Danis E, Bozkurt M, Gurbuz A (2014) Diabetes mellitus as a risk factor for high grade renal cell carcinoma. Asian Pac J Cancer Prev 15(9):3993–3996CrossRefPubMedGoogle Scholar
  15. 15.
    Schrem H, Kurok M, Kaltenborn A, Vogel A, Walter U, Zachau L, Manns MP, Klempnauer J, Kleine M (2013) Incidence and long-term risk of de novo malignancies after liver transplantation with implications for prevention and detection. Liver Transpl 19(11):1252–1261CrossRefPubMedGoogle Scholar
  16. 16.
    Leveridge M, Musquera M, Evans A, Cardella C, Pei Y, Jewett M, Robinette M, Finelli A (2011) Renal cell carcinoma in the native and allograft kidneys of renal transplant recipients. J Urol 186(1):219–223CrossRefPubMedGoogle Scholar
  17. 17.
    Grulich AE, van Leeuwen MT, Falster MO, Vajdic CM (2007) Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Lancet 370(9581):59–67CrossRefPubMedGoogle Scholar
  18. 18.
    Villeneuve PJ, Schaubel DE, Fenton SS, Shepherd FA, Jiang Y, Mao Y (2007) Cancer incidence among Canadian kidney transplant recipients. Am J Transplant 7(4):941–948CrossRefPubMedGoogle Scholar
  19. 19.
    Moudouni SM, Lakmichi A, Tligui M, Rafii A, Tchala K, Haab F, Gattegno B, Thibault P, Doublet JD (2006) Renal cell carcinoma of native kidney in renal transplant recipients. BJU Int 98(2):298–302CrossRefPubMedGoogle Scholar
  20. 20.
    Kasiske BL, Snyder JJ, Gilbertson DT, Wang C (2004) Cancer after kidney transplantation in the United States. Am J Transplant 4(6):905–913CrossRefPubMedGoogle Scholar
  21. 21.
    Adami J, Gäbel H, Lindelöf B, Ekström K, Rydh B, Glimelius B, Ekbom A, Adami HO, Granath F (2003) Cancer risk following organ transplantation: a nationwide cohort study in Sweden. Br J Cancer 89(7):1221–1227CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Penn I (1990) Cancers complicating organ transplantation. N Engl J Med 323(25):1767–1769CrossRefPubMedGoogle Scholar
  23. 23.
    Collett D, Mumford L, Banner NR, Neuberger J, Watson C (2010) Comparison of the incidence of malignancy in recipients of different types of organ: a UK Registry audit. Am J Transplant 10(8):1889–1896CrossRefPubMedGoogle Scholar
  24. 24.
    Hall EC, Pfeiffer RM, Segev DL, Engels EA (2013) Cumulative incidence of cancer after solid organ transplantation. Cancer 119(12):2300–2308CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Engels EA, Pfeiffer RM, Fraumeni JF Jr, Kasiske BL, Israni AK, Snyder JJ, Wolfe RA, Goodrich NP, Bayakly AR, Clarke CA, Copeland G, Finch JL, Fleissner ML, Goodman MT, Kahn A, Koch L, Lynch CF, Madeleine MM, Pawlish K, Rao C, Williams MA, Castenson D, Curry M, Parsons R, Fant G, Lin M (2011) Spectrum of cancer risk among US solid organ transplant recipients. JAMA 306(17):1891–1901CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Tsivian M, Caso JR, Kimura M, Polascik TJ (2013) Renal tumors in solid organ recipients: clinical and pathologic features. Urol Oncol 31(2):255–258CrossRefPubMedGoogle Scholar
  27. 27.
    Végsö G, Toronyi E, Hajdu M, Piros L, Görög D, Deák PA, Doros A, Péter A, Langer RM (2011) Renal cell carcinoma of the native kidney: a frequent tumor after kidney transplantation with favorable prognosis in case of early diagnosis. Transplant Proc 43(4):1261–1263CrossRefPubMedGoogle Scholar
  28. 28.
    Cheung CY, Lam MF, Lee KC, Chan GS, Chan KW, Chau KF, Li CS, Chan TM, Lai KN (2011) Renal cell carcinoma of native kidney in Chinese renal transplant recipients: a report of 12 cases and a review of the literature. Int Urol Nephrol 43(3):675–680CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Gigante M, Neuzillet Y, Patard JJ, Tillou X, Thuret R, Branchereau J, Timsit MO, Terrier N, Boutin JM, Sallusto F, Karam G, Barrou B, Chevallier D, Mazzola CR, Delaporte V, Doeffler A, Kleinclauss F, Badet L, the members of the Comité de Cancerologie de l'Association Française d'Urologie (CCAFU) and Comité de Transplantation de l'Association Française d'Urologie (CTAFU) (2012) Renal cell carcinoma (RCC) arising in native kidneys of dialyzed and transplant patients: are they different entities? BJU Int 110(11 Pt B):E570–E573CrossRefPubMedGoogle Scholar
  30. 30.
    Schwarz A, Vatandaslar S, Merkel S, Haller H (2007) Renal cell carcinoma in transplant recipients with acquired cystic kidney disease. Clin J Am Soc Nephrol 2:750–756CrossRefPubMedGoogle Scholar
  31. 31.
    Karczewski M, Rzymski P, Karczewski J (2012) De novo renal cell carcinoma of native kidneys in renal transplant recipients: a single-center experience. Exp Clin Transplant 10(4):310–313CrossRefPubMedGoogle Scholar
  32. 32.
    Denton MD, Magee CC, Ovuworie C, Mauiyyedi S, Pascual M, Colvin RB, Cosimi AB, Tolkoff-Rubin N (2002) Prevalence of renal cell carcinoma in patients with ESRD pre-transplantation: a pathologic analysis. Kidney Int 61(6):2201–2209CrossRefPubMedGoogle Scholar
  33. 33.
    Hofmann JN, Schwartz K, Chow WH, Ruterbusch JJ, Shuch BM, Karami S, Rothman N, Wacholder S, Graubard BI, Colt JS, Purdue MP (2013) The association between chronic renal failure and renal cell carcinoma may differ between black and white Americans. Cancer Causes Control 24(1):167–174CrossRefPubMedGoogle Scholar
  34. 34.
    Hurst FP, Jindal RM, Graham LJ, Falta EM, Elster EA, Stackhouse GB, Agodoa LY, Lentine KL, Salifu MO, Abbott KC (2010) Incidence, predictors, costs, and outcome of renal cell carcinoma after kidney transplantation: USRDS experience. Transplantation 90(8):898–904PubMedGoogle Scholar
  35. 35.
    Stewart JH, Vajdic CM, van Leeuwen MT, Amin J, Webster AC, Chapman JR, McDonald SP, Grulich AE, McCredie MR (2009) The pattern of excess cancer in dialysis and transplantation. Nephrol Dial Transplant 24(10):3225–3231CrossRefPubMedGoogle Scholar
  36. 36.
    Vajdic CM, McDonald SP, McCredie MR, van Leeuwen MT, Stewart JH, Law M, Chapman JR, Webster AC, Kaldor JM, Grulich AE (2006) Cancer incidence before and after kidney transplantation. JAMA 296(23):2823–2831CrossRefPubMedGoogle Scholar
  37. 37.
    Maisonneuve P, Agodoa L, Gellert R, Stewart JH, Buccianti G, Lowenfels AB, Wolfe RA, Jones E, Disney AP, Briggs D, McCredie M, Boyle P (1999) Cancer in patients on dialysis for end-stage renal disease: an international collaborative study. Lancet 354(9173):93–99CrossRefPubMedGoogle Scholar
  38. 38.
    Lee HH, Choi KH, Yang SC, Han WK (2012) Renal cell carcinoma in kidney transplant recipients and dialysis patients. Korean J Urol 53(4):229–233CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Goh A, Vathsala A (2011) Native renal cysts and dialysis duration are risk factors for renal cell carcinoma in renal transplant recipients. Am J Transplant 11(1):86–92CrossRefPubMedGoogle Scholar
  40. 40.
    Demir T, Ozel L, Gökçe AM, Ata P, Kara M, Eriş C, Özdemir E, Titiz MI (2015) Cancer screening of renal transplant patients undergoing long-term immunosuppressive therapy. Transplant Proc 47(5):1413–1417CrossRefPubMedGoogle Scholar
  41. 41.
    Hoshida Y, Tsukuma H, Yasunaga Y, Xu N, Fujita MQ, Satoh T, Ichikawa Y, Kurihara K, Imanishi M, Matsuno T, Aozasa K (1997) Cancer risk after renal transplantation in Japan. Int J Cancer 71(4):517–520CrossRefPubMedGoogle Scholar
  42. 42.
    Lien YH, Hunt KR, Siskind MS, Zukoski C (1993) Association of cyclosporin A with acquired cystic kidney disease of the native kidneys in renal transplant recipients. Kidney Int 44(3):613–616CrossRefPubMedGoogle Scholar
  43. 43.
    Yokoyama I, Hayashi S, Kobayashi T, Negita M, Yasutomi M, Uchida K, Takagi H (1995) Immunosuppressive drugs and their effect on experimental tumor growth. Transpl Int 8(4):251–255CrossRefPubMedGoogle Scholar
  44. 44.
    Koehl GE, Wagner F, Stoeltzing O, Lang SA, Steinbauer M, Schlitt HJ, Geissler EK (2007) Mycophenolate mofetil inhibits tumor growth and angiogenesis in vitro but has variable antitumor effects in vivo, possibly related to bioavailability. Transplantation 83(5):607–614CrossRefPubMedGoogle Scholar
  45. 45.
    Kaltenborn A, Schrem H (2013) Mycophenolate mofetil in liver transplantation: a review. Ann Transplant 18:685–696CrossRefPubMedGoogle Scholar
  46. 46.
    O'Neill JO, Edwards LB, Taylor DO (2006) Mycophenolate mofetil and risk of developing malignancy after orthotopic heart transplantation: analysis of the transplant registry of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant 25(10):1186–1191CrossRefPubMedGoogle Scholar
  47. 47.
    Penn I (2000) Post-transplant malignancy: the role of immunosuppression. Drug Saf 23:101–113CrossRefPubMedGoogle Scholar
  48. 48.
    Buell JF, Gross TG, Woodle ES (2005) Malignancy after transplantation. Transplantation 80(2 Suppl):S254–S264CrossRefPubMedGoogle Scholar
  49. 49.
    Alberú J, Pascoe MD, Campistol JM, Schena FP, Rial Mdel C, Polinsky M, Neylan JF, Korth-Bradley J, Goldberg-Alberts R, Maller ES, Sirolimus CONVERT Trial Study Group (2011) Lower malignancy rates in renal allograft recipients converted to sirolimus-based, calcineurin inhibitor-free immunotherapy: 24-month results from the CONVERT trial. Transplantation 92(3):303–310CrossRefPubMedGoogle Scholar
  50. 50.
    Mathew T, Kreis H, Friend P (2004) Two-year incidence of malignancy in sirolimus-treated renal transplant recipients: results from five multicenter studies. Clin Transpl 18(4):446–449CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of General, Visceral and Transplant SurgeryHannover Medical SchoolHannoverGermany
  2. 2.Department of UrologySt. Antonius HospitalGronauGermany
  3. 3.Department of Urology and Urological OncologyHannover Medical SchoolHannoverGermany
  4. 4.Department of NephrologyHannover Medical SchoolHannoverGermany
  5. 5.Core Facility Quality Management and Health Technology Assessment in Transplantation, Integrated Research and Treatment Facility Transplantation (IFB-Tx)Hannover Medical SchoolHannoverGermany

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