Abstract
Renal cancer occurs more frequently in renal transplanted patients than in the general population, affecting native kidneys in 90 % of cases and the graft in 10 %. In addition to general risk factors, malignancy susceptibility may be influenced by immunosuppressive therapy, the use of calcineurin inhibitors (CNI) as compared with mammalian target of rapamycin inhibitors, and the length of dialysis treatment. Acquired cystic kidney disease may increase the risk for renal cancer after transplantation, while autosomal dominant polycystic kidney disease does not seem to predispose to cancer development. Annual ultrasound evaluation seems appropriate in patients with congenital or acquired cystic disease or even a single cyst in native kidneys, and every 2 years in patients older than 60 years if they were on dialysis for more than 5 years before transplantation. Immunosuppression should be lowered in patients who develop renal cancer, by reduction or withdrawal of CNI. Although more evidence is still needed, it seems reasonable to shift patients from CNI to everolimus or sirolimus if not already treated with one of these drugs, with due caution in subjects with chronic allograft nephropathy.
Similar content being viewed by others
References
Vajdic CM, Grulich AE, Kaldor JM et al (2006) Specific infections, infection-related behavior, and risk of non-Hodgkin lymphoma in adults. Cancer Epidemiol Biomark Prev 15(6):1102–1108
Tillou X, Chahwan C, Le Gal S, Bensadoun H, Doerfler A (2014) Prostatectomy for localized prostate cancer to prepare for renal transplantation in end-stage renal disease patients. Ann Transplant 19:569–575
Piselli P, Serraino D, Segoloni GP et al (2012) Risk of de novo cancers after transplantation: results from a cohort of 7217 kidney transplant recipients, Italy 1997–2009. Eur J Cancer 49(2):336–344
Wisgerhof HC, van der Geest LG, de Fijter JW et al (2011) Incidence of cancer in kidney-transplant recipients: a long-term cohort study in a single center. Cancer Epidemiol 35(2):105–111
Farrugia D, Mahboob S, Cheshire J et al (2014) Malignancy-related mortality following kidney transplantation is common. Kidney Int 85(6):1395–1403
Tsaur I, Obermüller N, Jonas D et al (2010) De novo renal cell carcinoma of native and graft kidneys in renal transplant recipients. BJUI 108:229–234
Ploussard G, Chambade D, Meria P et al (2012) Biopsy-confirmed de novo renal cell carcinoma (RCC) in renal grafts: a single-centre management experience in a 2396 recipient cohort. BJU Int 109(2):195–199
Hall S, Critcher C, Jefferson T, Clarke J, Roberts B (2013) Policing the crisis: mugging, the state and law and order, 2nd edn. Palgrave Macmillan, Basingstoke
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 370:59–67
Guba M, Löhe F (2004) Transplantation in cancer disease, and tumors in organ transplantation: current aspects and future prospects. MMW Fortschr Med 146(24):32–34
Bustami RT, Ojo AO, Wolfe RA, Merion RM, Bennett WM, McDiarmid SV, Leichtman AB, Held PJ, Port FK (2004) Immunosuppression and the risk of post-transplant malignancy among cadaveric first kidney transplant recipients. Am J Transplant 4(1):87–93
Gallagher MP, Kelly PJ, Jardine M et al (2010) Long-term cancer risk of immunosuppressive regimens after kidney transplantation. J Am Soc Nephrol 21(5):852–858
Salgo R, Gossmann J, Schöfer H et al (2010) Switch to a sirolimus-based immunosuppression in long-term renal transplant recipients: reduced rate of pre-malignancies and nonmelanoma skin cancer in a prospective, randomized, assessor-blinded, controlled clinical trial. Am J Transplant 10(6):1385–1393
Euvrard S, Morelon E, Rostaing L et al (2012) Sirolimus and secondary skin-cancer prevention in kidney transplantation. N Engl J Med 367(4):329–339
Campbell SB, Walker R, See Tai S, Jiang Q, Russ GR (2012) Randomized controlled trial of sirolimus for renal transplant. Am J Transpl 12:1146–1156
Hope CM, Grace BS, Pilkington KR et al (2014) The immune phenotype may relate to cancer development in kidney transplant recipients. Kidney Int 86:175–183
Hoogendijk-van den Akker JM, Harden PN, Hoitsma AJ et al (2013) 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(10):1317–1323
Carroll RP, Chapman JR (2013) Can the risk of skin cancer after transplantation be reduced by mTOR inhibitors? Am J Kidney Dis 61(5):698–700
Roederer M (2001) Spectral compensation for flow cytometry: visualization artifacts, limitations, and caveats. Cytometry 45:194–205
Ma MK, Lim WH, Turner RM, Chapman JR, Craig JC, Wong G (2014) The risk of cancer in recipients of living-donor, standard and expanded criteria deceased donor kidney transplants: a registry analysis. Transplantation 97(8):817–825
Stewart JH, Buccianti G, Agodoa L et al (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):197–207
Wong G, Hayen A, Chapman JR, Webster AC, Wang JJ, Mitchell P, Craig JC (2009) Association of CKD and cancer risk in older people. J Am Soc Nephrol 20(6):1341–1350
Wong G, Turner RM, Chapman JR, Howell M, Lim WH, Webster AC, Craig JC (2013) Time on dialysis and cancer risk after kidney transplantation. Transplantation 95(1):114–121
Grantham JJ (1991) Acquired cystic kidney disease. Kidney Int 40(1):143–152
Ishikawa I (1991) Acquired cystic disease: mechanisms and manifestations. Semin Nephrol 11(6):671–684
Matson MA, Cohen EP (1990) Acquired cystic kidney disease: occurrence, prevalence, and renal cancers. Medicine (Baltimore) 69(4):217–226
Narasimhan N, Golper TA, Wolfson M, Rahatzad M, Bennett WM (1986) Clinical characteristics and diagnostic considerations in acquired renal cystic disease. Kidney Int 30(5):748–752
Tonolini M, Rigiroli F, Villa F, Bianco R (2014) Complications of sporadic, hereditary, and acquired renal cysts: cross-sectional imaging findings. Curr Probl Diagn Radiol 43(2):80–90
Moore AE, Kujubu DA (2007) Spontaneous retroperitoneal hemorrhage due to acquired cystic kidney disease. Hemodial Int 11(Suppl 3):S38–S40
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(4):750–756
Chandhoke PS, Albala DM, Clayman RV (1992) Long-term comparison of renal function in patients with solitary kidneys and/or moderate renal insufficiency undergoing extracorporeal shock wave lithotripsy or percutaneous nephrolithotomy. J Urol 147(5):1226–1230
Doublet JD, Peraldi MN, Gattegno B, Thibault P, Sraer JD (1997) Renal cell carcinoma of native kidneys: prospective study of 129 renal transplant patients. J Urol 158(1):42–44
Goh BKP, Dean PG, Cosio FG, Gloor JM, Prieto M, Stegall MD (2011) Bilateral native ureteral ligation without nephrectomy in the management of kidney transplant recipients with native proteinuria. Am J Transplant 11:2747–2750
Wetmore JB, Calvet JP, Yu AS, Lynch CF, Wang CJ, Kasiske BL, Engels EA (2014) Polycystic kidney disease and cancer after renal transplantation. J Am Soc Nephrol 25(10):2335–2341
Hajj P, Ferlicot S, Massoud W et al (2009) Prevalence of renal cell carcinoma in patients with autosomal dominant polycystic kidney disease and chronic renal failure. Urology 74(3):631–634
Truong LD, Choi YJ, Shen SS, Ayala G, Amato R, Krishnan B (2003) Renal cystic neoplasms and renal neoplasms associated with cystic renal diseases: pathogenetic and molecular links. Adv Anat Pathol 10(3):135–159
Keith DS, Torres VE, King BF, Zincki H, Farrow GM (1994) Renal cell carcinoma in autosomal dominant polycystic kidney disease. J Am Soc Nephrol 4(9):1661–1669
Lane W, Lacefield E, Tran R, de Riese W (2011) The clinical association of autosomal dominant polycystic kidney disease and renal cell carcinoma. J Urol 1:11–14
Jilg CA, Drendel V, Bacher J et al (2013) Autosomal dominant polycystic kidney disease: prevalence of renal neoplasias in surgical kidney specimens. Nephron Clin Pract 123(1–2):13–21
Perrone RD, Ruthazer R, Terrin NC (2001) Survival after end-stage renal disease in autosomal dominant polycystic kidney disease: contribution of extrarenal complications to mortality. Am J Kidney Dis 38(4):777–784
Regan RJ, Abercrombie GF, Lee HA (1977) Polycystic renal disease—occurrence of malignant change and role of nephrectomy in potential transplant recipients. Br J Urol 49(2):85–91
Ng RC, Suki WN (1980) Renal cell carcinoma occurring in a polycystic kidney of a transplant recipient. J Urol 124(5):710–712
Hadimeri H, Nordén G, Friman S, Nyberg G (1997) Autosomal dominant polycystic kidney disease in a kidney transplant population. Nephrol Dial Transplant 12(7):1431–1436
Errasti P, Manrique J, Lavilla J et al (2003) Autosomal-dominant polycystic kidney disease: high prevalence of graft loss for death-related malignancies and cardiovascular risk factors. Transplant Proc 35(5):1717–1719
DeLong MJ, Schmitt D, Scott KM, Ramakumar S, Lien YH (2003) Multicentric papillary renal carcinoma in renal allograft. Am J Kidney Dis 42(2):381–384
Hajj P, Ferlicot S, Massoud W et al (2009) Prevalence of renal cell carcinoma in patients with autosomal dominant polycystic kidney disease and chronic renal failure. Urology 74(3):631–634
Patel P, Horsfield C, Compton F, Taylor J, Koffman G, Olsburgh J (2011) Native nephrectomy in transplant patients with autosomal dominant polycystic kidney disease. Ann R Coll Surg Engl 93(5):391–395
Ward CJ, Wu Y, Johnson RA et al (2011) Germline PKHD1 mutations are protective against colorectal cancer. Hum Genet 129(3):345–349
Kasiske BL, Vazquez MA, Harmon WE et al (2000) Recommendations for the outpatient surveillance of renal transplant recipients. J Am Soc Nephrol 11(Suppl 15):S1–S86
Renal Physicians Association/American Society of Nephrology Working Group (2000) Clinical practice guidelines on shared decision-making in the appropriate initiation of and withdrawal from dialysis. J Am Soc Nephrol 11(7):1340–1342 (erratum: 11(9):2, following 1788)
Kidney Disease Improving Global Outcomes (KDIGO) Transplant Work Group, Kasiske BL, Zeier MG et al (2009) KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transpl 9(Suppl 3):S89–S90
Heinz-Peer G, Mostbeck GH, Banyai S, Helbich T, Turetschek K, Kainberger F (1995) Malignant neoplasms after kidney transplantation: value of an annual radiological screening program. Rofo 163(3):250–255
Kalbe T, Fulda G, Benoit M et al (2005) European Association of Urology guidelines on renal transplantation. Euro Urol 47(2):156–166
Wong G, Howard K, Webster AC, Chapman JR, Craig JC (2010) Screening for renal cancer in recipients of kidney transplants. Nephrol Dial Transpl 26(5):1729–1739
Goh BKP, Dean PG, Cosio FG, Gloor JM, Prieto M, Stegall MD (2011) Bilateral native ureteral ligation without nephrectomy in the management of kidney transplant recipients with native proteinuria. Am J Transpl 11:2747–2750
Campbell SC, Novick AC, Belldegrun A et al (2009) Guideline for management of the clinical T1 renal mass. Practice Guidelines Committee of the American Urological Association. J Urol 82:1271–1279
Badalato GM, Kates M, Wisnivesky JP, Choudhury AR, McKiernan JM (2012) Survival after partial and radical nephrectomy for the treatment of stage T1bN0M0 renal cell carcinoma (RCC) in the USA: a propensity scoring approach. BJU Int 109(10):1457–1462
Weight CJ, Larson BT, Gao T et al (2010) Elective partial nephrectomy in patients with clinical T1b renal tumors is associated with improved overall survival. Urology 76(3):631–637
Kaouk JH, Spana G, Hillyer SP, White MA, Haber GP, Goldfarb D (2011) Robotic-assisted laparoscopic partial nephrectomy for a 7-cm mass in a renal allograft. Am J Transpl 11(10):2242–2246
Kutikov A, Uzzo RG (2009) The R.E.N.A.L. nephrometry score: a comprehensive standardized system for quantitating renal tumor size, location and depth. J Urol 182(3):844–853
Ficarra V, Novara G, Secco S et al (2009) Preoperative aspects and dimensions used for an anatomical (PADUA) classification of renal tumours in patients who are candidates for nephron-sparing surgery. Eur Urol 56(5):786–793
Simmons MN, Ching CB, Samplaski MK, Park CH, Gill IS (2010) Kidney tumor location measurement using the C index method. J Urol 183(5):1708–1713
Okhunov Z, Rais-Bahrami S, George AK et al (2011) The comparison of three renal tumor scoring systems: C-Index, P.A.D.U.A., and R.E.N.A.L. nephrometry scores. J Endourol 25(12):1921–1924
Hew MN, Baseskioglu B, Barwari K et al (2011) Critical appraisal of the PADUA classification and assessment of the R.E.N.A.L. nephrometry score in patients undergoing partial nephrectomy. J Urol 186(1):42–46
Rosevear HM, Gellhaus PT, Lightfoot AJ, Kresowik TP, Joudi FN, Tracy CR (2012) Utility of the RENAL nephrometry scoring system in the real world: predicting surgeon operative preference and complication risk. BJU Int 109(5):700–705
Simhan J, Smaldone MC, Tsai KJ et al (2011) Objective measures of renal mass anatomic complexity predict rates of major complications following partial nephrectomy. Eur Urol 60(4):724–730
Brugarolas JB, Vazquez F, Reddy A, Sellers WR, Kaelin WG Jr (2003) TSC2 regulates VEGF through mTOR-dependent and -independent pathways. Cancer Cell 4:147–158
Escudier B, Porta C, Schmidinger M et al. ESMO Guidelines Working Group (2014). Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol Sep 25(Suppl 3):iii49–56
Robinson ES, Matulonis UA, Ivy P, Berlin ST, Tyburski K, Penson RT, Humphreys BD (2010) Rapid development of hypertension and proteinuria with cediranib, an oral vascular endothelial growth factor receptor inhibitor. Clin J Am Soc Nephrol 5:477–478
Gurevich F, Perazella MA (2009) Renal effects of anti-angiogenesis therapy: update for the internist. Am J Med 122:322–328
Eremina V, Quaggin SE (2010) Biology of anti-angiogenic therapy-induced thrombotic microangiopathy. Semin Nephrol 30:582–590
Escudier B, Pluzanska A, Koralewski P et al (2007) AVOREN Trial investigators. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet 370:2103–2111
Rixe O, Bukowski RM, Michaelson MD et al (2007) Axitinib treatment in patients with cytokine-refractory metastatic renal-cell cancer: a phase II study. Lancet Oncol 8:975–984
Eremina V, Jefferson JA, Kowalewska J et al (2008) VEGF inhibition and renal thrombotic microangiopathy. N Engl J Med 358:1129–1136
Izzedine H, Escudier B, Rouvier P, Gueutin V, Varga A, Bahleda R, Soria JC (2013) Acute tubular necrosis associated with mTOR inhibitor therapy: a real entity biopsy-proven. Ann Oncol 24:2421–2425
Guba M, von Breitenbuch P, Steinbauer M et al (2002) Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor. Nat Med 8:128–135
Alberú J, Pascoe MD, Campistol JM et al (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):303–310
Schena FP, Pascoe MD, Alberu J et al (2009) Conversion from calcineurin inhibitors to Sirolimus maintenance therapy in renal allograft recipients: 24-month efficacy and safety results from the CONVERT trial. Transplantation 87:233–242
Acknowledgments
This paper was promoted by the “Onco-Nephrology Working Group” coordinated by Maurizio Gallieni under the auspices of the Italian Society of Nephrology (SIN), chaired by Giovanbattista Capasso and the Italian Association of Medical Oncology (AIOM), chaired by Stefano Cascinu.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Informed consent
For this type of study formal consent is not required.
Research involving human participants and/or animals
This article does not contain any studies with human participants or animals performed by any of the authors.
Rights and permissions
About this article
Cite this article
Frascà, G.M., Sandrini, S., Cosmai, L. et al. Renal cancer in kidney transplanted patients. J Nephrol 28, 659–668 (2015). https://doi.org/10.1007/s40620-015-0219-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40620-015-0219-8