Alves, R

Baptista, C

Bastos, C

Bastos, M

Campos, MV

Carvalheiro, M

Freitas, L

Furtado, AL

Leitão, P

Lemos, MC

Mota, A

Repositório Institucional dos Hospitais da Universidade de Coimbra

Kidney Transplantation and Diabetes: Posttransplantation MalignancyM. Bastos, C. Baptista, M.V. Campos, R. Alves, L. Freitas, C. Bastos, P. Leita˜o, M. Lemos, A. Mota,L. Furtado, and M. CarvalheiroTHE DEVELOPMENT of de novo malignancies inkidney transplant recipients represents a major prob-lem. The reported prevalence is between 1% and 16% inWestern countries and 1% to 3% in Asian countries.1–3 Inour Center, the overall prevalence of 7.13% was reported in1997 by Arnaldo et al.4 The most prevalent cancers aresquamous cell carcinomas and basal cell carcinomas of theskin with an increasing cumulative incidence with longersurvival of the patient.5,6 Epidemiological data show severalrisk factors, including pigmentary characteristics, solar irra-diation, viral warts, type and doses of long-term immuno-suppressants, presence of an oncogenic virus (Epstein-Barr), with age, with time of dialysis, genetic factors anddiabetes among other considerations. The posttransplanta-tion lymphoproliferative diseases, lymphoma, and Kaposi’ssarcoma are associated with the immunosuppressive ther-apy and oncogenic viruses.7–9 Type 2 diabetes mellitus(DM2) has been related to the risk for colon, endometrial,pancreatic, and hepatic cancers as well as an increased riskof non-Hodgkin’s lymphoma. Until now there are no re-ports of similar correlations with type 1 diabetes mellitus(DM1).10–12 Posttransplantation diabetes mellitus is insome ways similar to DM2, including insulin resistance andthe presence of an overweight or obesity situation, but thereare no reports on the prevalence of malignancy in thisgroup of patients. The aim of this study was to determinethe prevalence of malignancy during follow-up of all pa-tients with diabetes bearing a kidney transplant in ourCenter.PATIENTS AND METHODSBetween 1992 and 2001, 1070 patients underwent transplantationwith a kidney including, 55 (5.6%) diabetics: 33 with DM1, 22 withDM2, and 109 (10.4%) with posttransplantation diabetes (PTDM).We reviewed the files of these patients and performed statisticalanalyses using mean and SD values with the chi-square test.RESULTSWe observed nine cases of malignancies (5.6%), namely sixmen and three women. Two patients had DM1 (6.1%), onepatient had DM2 (4.5%), and six patients had PTDM(5.7%). The types of cancer, included single cases ofmultiple myeloma, non-Hodgkin’s lymphoma, melanoma,skin basal cell cancer, breast cancer, laryngeal cancer, andlung small-cells cancer as well as two cases of skin squamouscell cancer (Table 1). The mean age at diagnosis was 49.2years (range: 28 to 63 years), the mean duration of thekidney transplant was 58.7 months (range: 27 to 108months), although in seven cases it occurred at more than36 months. The mean creatininemia at diagnosis was 1.1mg/dL (range: 0.8 to 2 mg/dL). The immunosuppressivetherapy was a triple-regimen in 66.6% of patients usingazathioprine or mycophenolate together with oral methyl-prednisolone and cyclosporine. In 33.3% of patients it wasdouble-therapy with methylprednisolone and cyclosporine.The follow-up revealed four deaths. Among the five livingpatients, two have returned to dialysis and three havefunctioning grafts.DISCUSSIONThe causes of cancer are multifactorial. Several risk factorshave been reported, including type and cumulative dose ofimmunosuppressive agents, age, sex, duration of dialysis,smoking, obesity, sunlight exposure, oncogenic virus(EBNA, cytomegalovirus), diabetes, world region and ge-netic factors. The prevalence in our patients was 5.6%, arate similar to other reports. The risk increased after 36months posttransplantation. Reduction in immunosuppres-sion was performed in all patients; some returned todialysis. This posttransplantation complication shows a highmortality rate and poses problems with immunosuppres-sion.7 Tumors diagnosed before 100 days after transplanta-tion may be viewed as previously existent or possiblydonor-transmitted malignancies, a particular problem witholder cadaveric donors. We must be alert for the potentialrisk of donor-transmited malignancies, which are associatedwith a high incidence of disseminated disease and mortalityin recipients.13 The outcome of a malignancy depends onseveral factors: the type of cancer, the time of diagnosis andthe delay to therapy. Early diagnosis and treatment areFrom the Departments of Endocrinologia and Diabetes (M.B.,C.B., M.V.C., P.L., M.L., M.C.), Nefrologia (R.A., L.F.) and Uro-logia and Transplantac¸a˜o (C.B., A.M., L.F.), Hospitais da Univer-sidade de Coimbra, Coimbra, Portugal.Address reprint requests to M. Bastos, S. Endocrinologia eDiabetes, Hospitais da Universidade de Coimbra, Praceta MotaPinto 3000-075 Coimbra, Portugal.0041-1345/03/$–see front matter © 2003 by Elsevier Science Inc.doi:10.1016/S0041-1345(03)00324-5 360 Park Avenue South, New York, NY 10010-17101098 Transplantation Proceedings, 35, 1098–1099 (2003)essential for a satisfactory outcome, so a regular screeningexamination is recommended for all patients bearing akidney transplant.14REFERENCES1. Min SK, Huh S, Ahn MS, et al: Transplant Proc 32:1980, 20002. Park JH, Bok HJ, Kim BS, et al: Transplant Proc 32:1979,20003. Min SK, Huh S, Ahn MS, et al: Transplant Proc 32:1980, 20004. Arnaldo et al: Presented at the Congresso Portugueˆs deTransplantac¸a˜o, December 18–20, 19975. Naldi L, Fortina AB, Lovati S, et al: Transplantation 70:1479,20006. Harden PN, Fryer AA, Reece S, et al: Transplant Proc33:1302, 20017. Chisholm MA: Pharm D 2(2), 2001. 2001 Medscape PortalsInc. Available from: URL http:www.medscape.com/viewarticle/4085868. Canfield CW, Hudnall SD, Collona JO, et al: Clin Transplant6:1, 19929. Mattila PS, Aalto SM, Heikkila L, et al: Clin Transplant15:337, 200110. Hjalgrim H, Frish M, Ekbom A, et al: J Intern Med 241:471,199711. Howard D, Strikler MPH, Judith W-R, et al: DiabetesTechnol Therap 3,2:263, 200112. Kath R, Schiel R, Muller UA, et al: J Cancer Res Clin Oncol126:412, 200013. Robert J, Stratta MD: Medscape Transplant 2001. Availablefrom: URL http:www.medscape.com/medscape/transplantation/journal/2001/v02.n05/mtl016.stra14. Ishikawa N, Tanabe K, Tokumoto T, et al: Transplant Proc32:1907, 2000Table 1. Patients with Diabetes Who Underwent Kidney Transplantation and MalignanciesCases Sex Age (y) Type of Diabetes Malignancy Treatment Outcome1 F 48 PTDM Lung small cell Chemotherapy Dead after 6 mo with functioning TX2 F 50 PTDM Multiple myeloma Chemotherapy Dead in 3 mo with functioning TX3 M 61 PTDM Non-Hodgkin’s lymphoma Radiotherapy Dead after 48 mo with functioning TX4 M 63 PTDM Skin squamous cell Surgery radiotherapy Alive with nonfunctioning TX5 M 59 PTDM Skin squamous cell Surgery Alive with functioning TX6 M 38 PTDM Skin basal cell Surgery Alive with nonfunctioning TX7 F 28 DM1 Breast Surgery Alive with functioning TX8 M 43 DM1 Laryngeal Surgery radiotherapy Alive with functioning TX9 M 53 DM2 Melanoma Surgery Dead after 11 mo with functioning TXAbbreviations: F, female; M, male.KIDNEY TRANSPLANTATION AND DIABETES 1099

Kidney transplantation and diabetes: posttransplantation malignancy

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Kidney transplantation and diabetes: posttransplantation malignancy

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