Malignancy-related mortality following kidney transplantation is common
2013; Elsevier BV; Volume: 85; Issue: 6 Linguagem: Inglês
10.1038/ki.2013.458
ISSN1523-1755
AutoresDaniela Farrugia, Sophia Mahboob, James Cheshire, Irena Begaj, Sajan Khosla, Daniel Ray, Adnan Sharif,
Tópico(s)Polyomavirus and related diseases
ResumoThere is a paucity of studies describing malignancy-related mortality after kidney transplantation. To help quantify this, we extracted data for all kidney-alone transplant procedures performed in England between April 2001 and March 2012. Data linkage analysis was performed between Hospital Episode Statistics and the Office for National Statistics to identify all deaths occurring in this cohort. Among 19,103 kidney transplant procedures analyzed (median follow-up 4.4 years), 2085 deaths occurred, of which 376 (18.0%) were due to malignancy (crude mortality rate 361 malignancy-related deaths per 100,000 person-years). Common sites of malignancy-related death were lymphoma (18.4%), followed by lung (17.6%) and renal (9.8%), with 14.1% unspecified. The risk of malignancy-related death increased with age: under 50 (0.8%), 50–59 (2.5%), 60–69 (4.8%), 70–79 (6.5%) and over 80 years (9.1%). Age- and gender-stratified malignancy-related mortality risk difference was higher in the transplant compared with the general population. Cox proportional hazard models identified increased age, pretransplant history of malignancy and deceased-donor kidney transplantation to be independently associated with risk for post-transplant death from malignancy. Thus, malignancy as a cause of post-kidney transplantation death is common and requires heightened surveillance. There is a paucity of studies describing malignancy-related mortality after kidney transplantation. To help quantify this, we extracted data for all kidney-alone transplant procedures performed in England between April 2001 and March 2012. Data linkage analysis was performed between Hospital Episode Statistics and the Office for National Statistics to identify all deaths occurring in this cohort. Among 19,103 kidney transplant procedures analyzed (median follow-up 4.4 years), 2085 deaths occurred, of which 376 (18.0%) were due to malignancy (crude mortality rate 361 malignancy-related deaths per 100,000 person-years). Common sites of malignancy-related death were lymphoma (18.4%), followed by lung (17.6%) and renal (9.8%), with 14.1% unspecified. The risk of malignancy-related death increased with age: under 50 (0.8%), 50–59 (2.5%), 60–69 (4.8%), 70–79 (6.5%) and over 80 years (9.1%). Age- and gender-stratified malignancy-related mortality risk difference was higher in the transplant compared with the general population. Cox proportional hazard models identified increased age, pretransplant history of malignancy and deceased-donor kidney transplantation to be independently associated with risk for post-transplant death from malignancy. Thus, malignancy as a cause of post-kidney transplantation death is common and requires heightened surveillance. Kidney transplantation is widely attributed with an increased incidence of malignancy after transplantation versus the general population,1.Kasiske B.L. Snyder J.J. Gilbertson D.L. et al.Cancer after kidney transplantation in the United States.Am J Transplant. 2004; 4: 905-913Crossref PubMed Scopus (864) Google Scholar, 2.Vajdic C.M. McDonald S.P. McCredie M.R.E. et al.Cancer incidence before and after kidney transplantation.JAMA. 2006; 296: 2823-2831Crossref PubMed Scopus (861) Google Scholar, 3.Kyllonen L. Salmela K. Pukkala E. Cancer incidence in a kidney-transplanted population.Transpl Int. 2000; 13: S394-S398Crossref PubMed Scopus (129) Google Scholar and broadly on par with comparable immune deficiency states such as HIV/AIDS.4.Grulich A.E. van Leeuwen M.T. Falster M.O. et al.Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis.Lancet. 2007; 370: 59-67Abstract Full Text Full Text PDF PubMed Scopus (1679) Google Scholar The etiology of malignancy after transplant is primarily due to the effects of immunosuppression, with suggestions of an important interplay with viral pathogens that contributes to pathophysiology.5.Morath C. Mueller M. Goldschmidt H. et al.Malignancy in renal transplantation.J Am Soc Nephrol. 2004; 15: 1582-1588Crossref PubMed Scopus (186) Google Scholar By contrast, the literature on malignancy-related mortality after transplantation is scarce, with disparate mortality risk documented comparing solid organ transplant recipients to the general population.6.Na R. Grulich A.E. Meagher N.S. et al.De novo cancer-related death in australian liver and cardiothoracic transplant recipients.Am J Transplant. 2013; 13: 1296-1304Crossref PubMed Scopus (52) Google Scholar,7.Kiberd B.A. Rose C. Gill J.S. Cancer mortality in kidney transplantation.Am J Transplant. 2009; 9: 1868-1875Abstract Full Text Full Text PDF PubMed Scopus (82) Google Scholar A similar analysis in a different cohort of patients such as in the United Kingdom has not been undertaken to confirm these findings. In addition, no study has yet provided information on the site of malignancy-related mortality in kidney transplantation and whether site-specific cancer mortality can be stratified along demographic factors such as age, gender and/or ethnicity. To inform clinical practice, we undertook a population-based cohort analysis of all deaths occurring after kidney transplantation in England over the past decade to determine causes, classifications and predictors of malignancy-related mortality. The aim of our study was to determine the overall and site-specific risk for malignancy-related mortality after kidney transplantation. A total of 19,688 kidney transplant procedures in England were recorded in the Hospital Episode Statistics (HES) data for adult (18,499) and pediatric (n=1189) kidney allograft recipients—excluding those with missing demographic data (n=585), we had a cohort of 19,103 for further analysis (104,154 patient-years for entire study cohort). There was no missing data with regard to mortality events. Table 1 demonstrates baseline characteristics of our study cohort. The median age for the whole cohort was 45 years (interquartile range 34–55 years). In all, 11,673 (61.1%) of the study cohort were men, with 7430 (38.9%) women. Ethnic breakdown of the study cohort comprised of white (13,695, 71.7%), Black or Black British (934, 4.9%), Asian or Asian British (1704, 8.9%), Chinese (81, 0.4%), mixed (166, 0.9%), other ethnic group (350, 1.8%), and unknown (2173, 11.4%). Socioeconomic deprivation quintiles were (from most to least deprived, respectively): 1 (4203, 22.0%), 2 (4,197, 22.0%), 3 (3765, 19.7%), 4 (3490, 18.3%), and 5 (3448, 18.0%). Living donor transplantation occurred in 6262 (32.8%) of all kidney transplant procedures reported. Diabetes mellitus classification was the most common medical comorbidity recorded in 2968 (15.5%) of all kidney allograft recipients.Table 1Baseline characteristics of kidney allograft recipientsVariableProportion (%)Age (years) <509060 (47.6%) 50–594562 (23.9%) 60–693733 (19.5%) 70–791631 (8.5%) ≥80117 (0.6%)Gender Male11,673 (61.1%) Female7430 (38.9%)Ethnicity White13,695 (71.7%) Black/Black British934 (4.9%) Asian/Asian British1704 (8.9%) Chinese81 (0.4%) Mixed166 (0.9%) Other350 (1.8%) Unknown2173 (11.4%)Socioeconomic deprivation (IMD 2010) 1 (most deprived)4203 (22.0%) 24197 (22.0%) 33765 (19.7%) 43490 (18.3%) 5 (least deprived)3448 (18.0%)Donor Living6262 (32.8%) Deceased12,841 (67.2%)Abbreviation: IMD, index of multiple deprivation. Open table in a new tab Abbreviation: IMD, index of multiple deprivation. To verify the quality of the HES data, we extracted information from the UK National Transplant database to determine the number of transplants performed during the same time frame. During the time from April 2001 and March 2012, 19,405 kidney transplant procedures were registered (19,241 kidney alone, 49 en bloc kidneys and 115 double kidneys transplants). This identifies a small discrepancy of 283 kidney-alone transplant procedures that have been over-reported in the HES data in comparison to UK National Transplant Database records (concordance 98.6% between both data sets). However, it should be highlighted that HES data records ‘date of admission’, whereas UK National Transplant database registers ‘date of transplant’, which could contribute to this apparent incongruity. By cross-referencing both HES and Office for National Statistics (ONS) databases, we identified 2085 deaths that occurred after kidney transplantation with median follow-up 4.4 years (interquartile range 2.2–7.3 years). Follow-up time consisted of 104,154 patient-years, with similar 4.4 years median follow-up in patient-years. Three hundred and seventy-six deaths were due to malignancy (2.0% of overall study cohort and 18.0% of total deaths). This equates to a crude mortality rate of 361 malignancy-related deaths per 100,000 person-years in our study cohort. Only death from infection (20.8%, 416 deaths per 100,000 person-years) and cardiovascular disease (21.2%, 424 deaths per 100,000 person-years) was more frequently documented as the leading cause of death. The most common site of malignancy-related death was lymphoma (18.4% of all cancer-related deaths), followed by lung (17.6%) and renal (9.8%), respectively (14.1% were unspecified). Table 2 highlights the risk for malignancy-related death (all-cause and location-specific) for our study cohort stratified by age, gender, and ethnicity. Age was an important and strong risk factor for cancer-related death, with increasing risk for cancer-related death as age increased: <50 (0.8%), 50–59 (2.5%), 60–69 (4.8%), 70–79 (6.5%), and over 80 (9.1%). There were only five malignancy-related deaths in the pediatric cohort (aged under 18 years) and all were classified as caused by lymphoma. Table 2 demonstrates the split in location of malignancy-related deaths into three age brackets of <50, 50–69, and over 70 years, respectively.Table 2Incidence of malignancy-related death (and location) per 100,000 person-years stratified by age, sex, and ethnicityCancerAge (years)SexEthnicity 70MaleFemaleWhiteBlackAsianOtherUnknownAll145.5661.41396.8380.4330.5387.4265.0253.8314.9329.4Renal10.868.0179.139.329.636.622.123.135.042.1Upper GI7.757.235.833.014.829.844.211.50.014.0Lower GI6.257.2179.133.022.227.10.011.535.056.1Lung17.0133.4214.970.751.865.022.123.170.091.1Lymphoma57.381.671.669.261.769.166.234.6105.063.1Breast7.713.671.61.627.110.822.10.035.014.0GU (not renal)1.521.835.87.912.313.50.00.00.00.0Prostate0.08.2107.49.40.08.10.00.00.00.0Hematological4.619.10.07.912.312.20.00.00.07.0Skin0.027.271.611.012.314.922.111.50.00.0Pancreas7.724.535.812.617.317.60.00.00.00.0Liver0.024.535.89.49.910.80.00.035.00.0Female4.613.635.80.022.26.80.00.00.021.0OtheraEndocrine, brain, heart, mesothelioma, and testicular.1.521.835.812.64.912.20.00.00.07.0Unspecified18.689.8286.562.932.152.866.234.60.014.0Abbreviations: GI, gastrointestinal; GU, genitourinary.a Endocrine, brain, heart, mesothelioma, and testicular. Open table in a new tab Abbreviations: GI, gastrointestinal; GU, genitourinary. Lung cancer was the most common malignancy-related death in men (18.6% of all cancer deaths), with lymphoma cancer being the most common in women (18.7% of all cancer deaths). There was no significant difference in the rate of cancer-related death or location of cancer with ethnicity in our cohort, although a trend was observed toward less overall malignancy-related death in non-whites (1.3%) versus whites (2.1%) (P=0.077), respectively. In a comparative analysis of transplant versus general population, Figure 1 compares the age-stratified mortality risk difference between the transplant and general population and demonstrates higher malignancy-related mortality risk in the transplant cohort for the majority of age groups. Figure 2 compares gender-stratified mortality risk difference between the transplant and general cohort and again demonstrates higher malignancy-related mortality risk for both male and female kidney allograft recipients versus the general population. No comparative analysis for ethnicity was performed because of the absence of robust mortality data for England based on ethnicity.Figure 2Mortality risk ratio comparing kidney transplant versus general population in England (gender stratified).View Large Image Figure ViewerDownload (PPT) In addition to the above demographic stratifications, we compared live-donor versus deceased-donor kidney transplant recipients for risk of malignancy-related death. We found live-donor kidney allograft recipients had a lower risk of malignancy-related death versus deceased-donor kidney allograft recipients (1.1% vs. 2.4%, respectively; P<0.001). No difference was observed in location of malignancy-related death between live-donor versus deceased-donor kidney recipients (P=0.172). We undertook relative survival analysis to provide a measure of excess mortality caused by cancer in kidney allograft recipients versus patients in the general population and the output is outlined in Table 3. Relative excess risk in kidney allograft recipients was higher with increasing age and in female subjects (borderline significance), whereas it was lower beyond the first year post-transplantation and in the more contemporary era (2006–2012 vs. 2002–2006), although the latter was of borderline significance.Table 3Relative survival analysis of kidney allograft recipients versus comparative general population life tables from the Office of National StatisticsParameterRelative excess risk95% Confidence intervalP-valueFollow-up time 1 year1.00—— 2 years0.470.38–0.57<0.001 3 years0.470.38–0.58<0.001 4 years0.540.44–0.67<0.001 5 years0.560.45–0.71<0.001Gender Male1.00—— Female1.070.94–1.230.07Period 2002–20061.00—— 2006–20120.870.75–1.000.06Age group (years) 0–491.00—— 50–592.612.21–3.09<0.001 60–694.433.74–5.24<0.001 70–796.855.20–9.03<0.001 80 and over4.770.41–55.510.212 Open table in a new tab Only 74 recipients (0.4%) in this cohort had a pretransplantation history of malignancy. Recipients with pretransplant history of cancer had higher risk of post-transplant death from malignancy compared with those without any previous history (17.6% vs. 1.9%, P<0.001). Recipients with pretransplant history of cancer were more likely to die from renal malignancy compared with those without pretransplant cancer history (9.5% vs. 0.2%, P<0.001). Indeed over half of all malignancy-related deaths in recipients with pretransplant cancer history were renal in origin (53.8%) compared with 8.3% for those with no pretransplant cancer history (P<0.001). We were unable to ascertain pretransplant cancer location from HES data so were unable to determine if they corresponded to post-transplant cancer death locations. Kaplan–Meier survival analysis was performed to assess unadjusted difference in risk of malignancy-related death after kidney transplantation, with Figures 3 and 4 representing survival difference between different ages and previous cancer history, respectively, among our English transplant cohort. Cox proportional hazard modeling was performed to assess the impact of competing and confounding variables upon malignancy-related mortality. Variables found to be independently associated with increased cancer mortality risk after kidney transplantation in England over the past decade included increased age, receipt of a deceased-donor kidney, and pre-transplant malignancy history (see Table 4). This remained the case in a competing risk analysis model assessing against the competing risk of other deaths versus malignancy-related deaths (see Supplementary Figure S1 online).Figure 4Kaplan–Meier plot of risk for malignancy-related death after kidney transplantation in England (between 2001 and 2012) stratified by history of pretransplant cancer.View Large Image Figure ViewerDownload (PPT)Table 4Cox regression proportional hazard model analysis of malignancy-related mortality after kidney transplantationVariableHazard ratio95% Confidence intervalP-valueAge (years) 70+1.000—— 50–690.4150.292–0.590<0.001 <500.0840.057–0.125<0.001Medical comorbidities Cerebral vascular accident2.0691.124–3.8100.020 Cancer7.6534.231–13.844<0.001Living donor transplant0.7020.537–0.9180.010 Open table in a new tab Download .jpg (.05 MB) Help with files Supplementary Figure 1 This study demonstrates that malignancy is a common cause of death among kidney allograft recipients, with similar incidence to cardiovascular events and infection as a cause of death after kidney transplantation. Malignancy-related mortality risk difference, stratified by both age and gender, was higher in our transplant cohort in comparison to the general population. The most frequently documented sites of malignancy on death certification were post-transplant lymphoproliferative disease, lung and renal. Pretransplant history of malignancy was a strong risk factor for malignancy-related death after transplantation, with over half of malignancy-related deaths within this cohort due to renal cancer. Finally, Cox regression analysis identified increasing age, deceased-donor kidney transplantation, and previous history of either malignancy or cerebrovascular accident as independent factors associated with risk for malignancy-related death after kidney transplantation. The literature predominantly focuses on incidence of malignancy after kidney transplantation, which has been clearly demonstrated to increase after kidney transplantation for the majority of cancers (often driven by a viral etiology). Sampaio et al.8.Sampaio M.S. Cho Y.W. Qazi Y. et al.Posttransplant malignancies in solid organ adult recipients: an analysis of the US National Transplant Database.Transplantation. 2012; 94: 990-998Crossref PubMed Scopus (145) Google Scholar recently described the incidence of malignancies after kidney transplantation in the United States Renal Data System and cited lymphoma, lung, prostate, and kidney as the four most common malignancies (similar to mortality rates in our analysis). Our study both complements and contradicts the few publications that have explored cancer mortality rates after kidney transplantation. Kiberd et al.7.Kiberd B.A. Rose C. Gill J.S. Cancer mortality in kidney transplantation.Am J Transplant. 2009; 9: 1868-1875Abstract Full Text Full Text PDF PubMed Scopus (82) Google Scholar identified 1937 malignancy-related death among 164,078 first kidney allograft recipients recorded in the United States Renal Data System between January 1990 and December 2004. They demonstrated no difference between the expected and observed cancer mortality rate, with equivalent standardized cancer mortality ratios with the general population. Therefore, although malignancy incidence may be increased versus the general population, actual malignancy-related mortality rate is the same. The explanation from Kiberd et al.7.Kiberd B.A. Rose C. Gill J.S. Cancer mortality in kidney transplantation.Am J Transplant. 2009; 9: 1868-1875Abstract Full Text Full Text PDF PubMed Scopus (82) Google Scholar to explain this paradox is that there are likely to be competing risks for death for kidney allograft recipients. By contrast our results suggest that malignancy-related mortality rates are higher among kidney allograft recipient versus the general population stratified by age and gender, in keeping with malignancy-related mortality risk reported in liver and cardiothoracic transplant recipients.6.Na R. Grulich A.E. Meagher N.S. et al.De novo cancer-related death in australian liver and cardiothoracic transplant recipients.Am J Transplant. 2013; 13: 1296-1304Crossref PubMed Scopus (52) Google Scholar There are many explanations for the differing results between the two kidney transplantation studies. The methodology and patient selection reflects different study cohorts; Kiberd and co-workers analyzed first kidney allograft recipients only within the United States (1990–2004), whereas our cohort included any kidney allograft recipient within England (2001–2012). The different time era will likely reflect different immunosuppression, postoperative management, donor/recipient selection, and so on that will make a direct comparison between the two study cohorts difficult. In addition, we would recommend cautious interpretation of our comparison between transplant versus general population malignancy-related mortality data. Making direct comparisons between the transplant and general population is flawed, as adjustments cannot be fully made for certain types of people that are over-represented in a specific cohort. For example, some of the lifestyle factors and illnesses that increase the likelihood that a person will subsequently need a transplant also increase the likelihood of dying of cancer independently of the transplant. Without the ability to adjust for these factors using further standardization, we cannot ascertain if the difference in crude cancer mortality rates are due to the prevalence of risk factors in the population groups rather than the milieu of after kidney transplantation immunosuppression. Both Kiberd et al.’s and our analysis confirmed older age and previous cancer history as independent predictors of malignancy-related death. However, our results also differ with regard to the impact of previous cerebrovascular accident, with our analysis suggesting an increased risk for malignancy-related death and data from Kiberd and co-workers suggesting a decreased risk. The links between stroke and cancer are well documented in the medical literature,9.Grisold W. Oberndorfer S. Struhal W. Stroke and cancer: a review.Acta Neurol Scand. 2009; 119: 1-16Crossref PubMed Scopus (175) Google Scholar, 10.Lee A.Y. Levine M.N. Venous thromboembolism and cancer: risks and outcomes.Circulation. 2003; 107: 117-121Crossref Google Scholar, 11.Schwarzbach C.J. Schaefer A. Ebert A. et al.Stroke and cancer: the importance of cancer-associated hypercoagulation as a possible stroke etiology.Stroke. 2012; 43: 3029-3034Crossref PubMed Scopus (181) Google Scholar with malignancy firmly established as promoting a hypercoagulation state that increases risk of future arterial and venous thromboembolic events. However, Prandoni et al.12.Prandoni P. Lensing A.W.A. Buller H.R. et al.Deep-vein thrombosis and the incidence of subsequent symptomatic cancer.N Engl J Med. 1992; 327: 1128-1133Crossref PubMed Scopus (658) Google Scholar have also demonstrated an association in the opposite direction; they observed an increased risk of clinically overt malignancy in patients previously diagnosed with symptomatic, venographically proved deep-vein thrombosis. It could therefore be speculated that a similar risk may be associated with previous arterial thromboembolic events. We did not ascertain any significant difference in mortality rates for cancer stratified by ethnicity, although there was a trend for less cancer-related death in non-whites. Hall and co-workers13.Hall E.C. Segev D.L. Engels E.A. Racial/ethnic differences in cancer risk after kidney transplantation.Am J Transplant. 2013; 13: 714-720Crossref PubMed Scopus (22) Google Scholar demonstrated that, compared with white kidney allograft recipients, black kidney allograft recipients had a lower incidence of lymphoma (adjusted incidence rate ratio 0.60, P<0.001) but higher incidence of kidney (adjusted incidence rate ratio 2.09, P<0.001) and prostate cancer (adjusted incidence rate ratio 2.14, P<0.001). Webster et al.14.Webster A.C. Craig J.C. Simpson J.M. et al.Identifying high risk groups and quantifying absolute risk of cancer after kidney transplantation: a cohort study of 15183 recipients.Am J Transplant. 2007; 7: 2140-2151Crossref PubMed Scopus (229) Google Scholar reported cancer risk was increased with white ethnicity (hazard ratio 1.36, 95% confidence interval (CI): 1.12–1.89). In our analysis, not only was no statistically significant difference in mortality rate ascertained but also the trend for mortality comparing white versus black was reversed; compared with whites, black allograft kidney recipients had higher risk for death from lymphoma (25.0% vs. 16.8%) and lower risk for death from both kidney (8.3 vs. 9.4%) and prostate (0.0 vs. 2.1%) cancer. It is difficult to explain the conflicting results between our analysis and that from Hall and co-workers, but it is possible that risk of mortality does not follow difference in incidence. For example, data from the National Cancer Intelligence Network (Cancer Research UK) demonstrated that blacks versus whites had higher incidence for prostate cancer but 1- and 3-year relative survival was better.15.Cancer Incidence and Survival by Major Ethnic Group, England, 2002–2006 National Cancer Intelligence Network.http://publications.cancerresearchuk.org/downloads/product/CS_REPORT_INCSURV_ETHNIC.pdfDate: 2013Google Scholar In addition, the black population in the United Kingdom is ethnically different from the black population in the United States, due to geographically different historical migration, and does not serve as a direct comparison. Risk factors for malignancy-related mortality in our analysis are broadly similar to reported risk factors for incidence of malignancy after kidney transplantation. Webster et al.14.Webster A.C. Craig J.C. Simpson J.M. et al.Identifying high risk groups and quantifying absolute risk of cancer after kidney transplantation: a cohort study of 15183 recipients.Am J Transplant. 2007; 7: 2140-2151Crossref PubMed Scopus (229) Google Scholar identified increased malignancy risk after kidney transplantation with older age, previous cancer history, and white race, with decreased risk associated with diabetes-related end-stage kidney disease. The increased incidence of cancer after transplantation likely represents the biological rationale for increased cancer-related post-transplant mortality. In vitro studies suggest that the calcineurin inhibitors cyclosporine and tacrolimus, mainstay of contemporary immunosuppression, can promote carcinogenesis through the production of cytokines that regulate tumor growth (such as transforming growth factor-β), metastasis, and angiogenesis. However, there is a lack of clinical data to support a disparate cancer incidence between the two calcineurin inhibitors.16.Gallagher M.P. Kelly P.J. Jardine M. et al.Long-term cancer risk of immunosuppressive regimens after kidney transplantation.J Am Soc Nephrol. 2010; 21: 852-858Crossref PubMed Scopus (160) Google Scholar Malignancy after transplantation can also have different clinical features that may explain higher mortality. For example, central nervous system involvement with post-transplant lymphoproliferative disorders (which is frequently more aggressive and fatal) occurs in approximately 30% of cases, contrasting with 1% in the non-transplant population.17.Taylor A.L. Marcus R. Bradley J.A. Post-transplant lymphoproliferative disorders (PTLD) after solid organ transplantation.Crit Rev Oncol/Haematol. 2005; 56: 155-167Abstract Full Text Full Text PDF PubMed Scopus (337) Google Scholar The elevated risk for kidney cancer in kidney allograft recipients is well described.1.Kasiske B.L. Snyder J.J. Gilbertson D.L. et al.Cancer after kidney transplantation in the United States.Am J Transplant. 2004; 4: 905-913Crossref PubMed Scopus (864) Google Scholar, 2.Vajdic C.M. McDonald S.P. McCredie M.R.E. et al.Cancer incidence before and after kidney transplantation.JAMA. 2006; 296: 2823-2831Crossref PubMed Scopus (861) Google Scholar, 3.Kyllonen L. Salmela K. Pukkala E. Cancer incidence in a kidney-transplanted population.Transpl Int. 2000; 13: S394-S398Crossref PubMed Scopus (129) Google Scholar It is likely that there are transplant-specific risk factors for this increased risk rather than because of the state of immunedeficiency. For example, Grulich and co-workers4.Grulich A.E. van Leeuwen M.T. Falster M.O. et al.Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis.Lancet. 2007; 370: 59-67Abstract Full Text Full Text PDF PubMed Scopus (1679) Google Scholar demonstrated a significantly greater standardized incidence ratio for kidney cancer in transplant recipients (6.68, 95% CI: 5.69–8.08) versus people with HIV/AIDS ( standardized incidence ratio 1.50, 95% CI: 1.23–1.83) in a meta-analysis of 12 population-based studies.4.Grulich A.E. van Leeuwen M.T. Falster M.O. et al.Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis.Lancet. 2007; 370: 59-67Abstract Full Text Full Text PDF PubMed Scopus (1679) Google Scholar It was not possible from these data to determine whether the kidney cancer was from native or transplanted kidney organ, although the literature suggests that the latter is rare.18.Muruve N.A. Shoskes D.A. Genitourinary malignancies in solid organ transplant recipients.Transplantation. 2005; 80: 709Crossref PubMed Scopus (45) Google Scholar Increased incidence of renal malignancy is likely related to prolonged periods of dialysis and subsequent development of acquired cystic disease (with the potential for malignant transformation).18.Muruve N.A. Shoskes D.A. Genitourinary malignancies in solid organ transplant recipients.Transplantation. 2005; 80: 709Crossref PubMed Scopus (45) Google Scholar We can speculate that reduced cancer mortality among living kidney allograft recipients reflects increas
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