Original Clinical Science
Sex Difference for Urologic Malignancy Risk in Uremic Patients After Kidney Transplantation: A Population-based Study Jyh-Chang Hwang,1,2 Ming-Yan Jiang,1 Yi-Hua Lu,1 and Shih-Feng Weng2,3 Background. High urologic malignancy incidence has been reported in end-stage renal disease (ESRD) patients, especially of female sex. This study was undertaken to evaluate whether female recipients still carry an aggravated risk of this malignancy after kidney transplantation (KT). Methods. The claims data from the Bureau of National Health Insurance of Taiwan were used for analysis. All KT recipients who developed urologic malignancy from January 1, 1999, to December 31, 2007 (n = 2,245) were enrolled in this study. By means of propensity score, a database of 1:4 ratio random incident ESRD patients with matched age, sex, comorbidity rates, and dialysis to index date was used as control (non-KT group, n = 8,980). The last observation period ended on December 31, 2008. Results. The cumulative urologic malignancy incidence rate was significantly higher in female recipients after KT than their female ESRD counterparts without KT (P < 0.001). This gap became more prominent approximately 2 years after transplantation. No similar trend was detected in male KT patients (P = 0.13). Incidence rate ratio of urologic malignancy was significantly higher in female recipients (incidence rate ratio, 2.13; 95% confidence interval [95% CI], 1.53–2.97) than in their male counterparts (incidence rate ratio, 1.43; 95% CI, 0.90–2.25). From multivariate Cox proportional hazard regression tests, female (hazards ratio, 2.10; 95% CI, 1.52–2.95) but not male sex (hazards ratio, 1.47; 95% CI, 0.93–2.32) was determined to be an independent factor for the development of urologic malignancy after KT. After acquiring this malignancy, KT recipients did not have any advantage in cumulative survival compared to ESRD patients without KT (P = 0.07). Conclusion. Compared to males, female recipients tended to have a significantly higher urologic malignancy risk after KT.
(Transplantation 2015;99: 818–822)
C
ancer risk has been reported in end-stage renal disease (ESRD) patients.1-4 High urologic malignancy incidences were found in these patients treated with hemodialysis or peritoneal dialysis.5 Among these, more transitional cell carcinoma (TCC) was noted in Taiwan.6 Lower urine flow washout effect with chronic bladder irritation, longterm and inappropriate use of Chinese herbal drugs, analgesics, and heavy metal intoxication have been proposed as contributors.7-9 Owing to the improvement of immunosuppressant therapy, kidney transplantation (KT) has become the superior Received 24 April 2014. Revision requested 5 May 2014. Accepted 3 July 2014. 1
Division of Nephrology, Chi Mei Medical Center, Tainan, Taiwan.
2
Department of Hospital and Health Care Administration, Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
3
Division of Medical Research, Chi Mei Medical Center, Tainan, Taiwan.
The authors declare no conflicts of interest. The study was partially supported by grant CMFHR10082 from the hospital and supported by ministry of science and technology, Taiwan with grant number: MOST 103-2314-B-384-001.
option for renal replacement therapy. Patients’ survival has been prolonged after KT, but life expectancy is still far worse than for the general population.10 However, post-organ transplantation was also associated with higher incidence of malignancy,11 with incidence rates of urologic malignancy post-KT varying across countries.11,12 Urologic malignancies, especially TCC, were found to be an important complication after KT in China,13 where its incidence was found to be even higher than other parts of the world. Compared to the male sex, female ESRD patients on dialysis were reported to have a higher risk of urologic malignancy.5 Does this sex difference diminish or increase after KT? No answer has been documented yet. Few studies, especially large-scale analyses, have compared the sex discrepancy of this malignancy incidence between ESRD patients and post-KT recipients. In this study with population-based data, we compared the sex disparity in urologic malignancy incidence in those ESRD patients receiving successful KT in Taiwan from 1999 to 2007. The benefit for long-term survival of these recipients after developing urologic malignancy was also evaluated because KT has been reported to have a better survival compared to dialysis for ESRD patients.14
J.-C.H. participated in research design and article writing. M.-Y.J. participated in reference search and part of article writing. Y.-H.L. participated in performance of the research. S.-F.W. participated in data analysis and statistics.
RESULTS
Correspondence: Jyh-Chang Hwang, M.D., 901 Zhonghua Rd., Yongkang Dist., Tainan City, 71010, Taiwan. ([email protected]).
Baseline Demographic Differences Among ESRD Patients With and Without KT
Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
As shown in Table 1, both KT and non-KT patients were age-matched and sex-matched. The transplant patients had similar percentages of diabetes mellitus (DM), hypertension,
ISSN: 0041-1337/15/9904-818 DOI: 10.1097/TP.0000000000000406
818
www.transplantjournal.com
Transplantation
■
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
April 2015
■
Volume 99
■
Number 4
Hwang et al
© 2014 Wolters Kluwer
819
TABLE 1.
Demographic characteristics and comorbid disorders between the patients receiving KT and those of non-KT uremic patients
Age at index date, yr Age at index date, n (%)
Sex Difference for Urologic Malignancy Risk in Uremic Patients After Kidney Transplantation: A Population-based Study Jyh-Chang Hwang,1,2 Ming-Yan Jiang,1 Yi-Hua Lu,1 and Shih-Feng Weng2,3 Background. High urologic malignancy incidence has been reported in end-stage renal disease (ESRD) patients, especially of female sex. This study was undertaken to evaluate whether female recipients still carry an aggravated risk of this malignancy after kidney transplantation (KT). Methods. The claims data from the Bureau of National Health Insurance of Taiwan were used for analysis. All KT recipients who developed urologic malignancy from January 1, 1999, to December 31, 2007 (n = 2,245) were enrolled in this study. By means of propensity score, a database of 1:4 ratio random incident ESRD patients with matched age, sex, comorbidity rates, and dialysis to index date was used as control (non-KT group, n = 8,980). The last observation period ended on December 31, 2008. Results. The cumulative urologic malignancy incidence rate was significantly higher in female recipients after KT than their female ESRD counterparts without KT (P < 0.001). This gap became more prominent approximately 2 years after transplantation. No similar trend was detected in male KT patients (P = 0.13). Incidence rate ratio of urologic malignancy was significantly higher in female recipients (incidence rate ratio, 2.13; 95% confidence interval [95% CI], 1.53–2.97) than in their male counterparts (incidence rate ratio, 1.43; 95% CI, 0.90–2.25). From multivariate Cox proportional hazard regression tests, female (hazards ratio, 2.10; 95% CI, 1.52–2.95) but not male sex (hazards ratio, 1.47; 95% CI, 0.93–2.32) was determined to be an independent factor for the development of urologic malignancy after KT. After acquiring this malignancy, KT recipients did not have any advantage in cumulative survival compared to ESRD patients without KT (P = 0.07). Conclusion. Compared to males, female recipients tended to have a significantly higher urologic malignancy risk after KT.
(Transplantation 2015;99: 818–822)
C
ancer risk has been reported in end-stage renal disease (ESRD) patients.1-4 High urologic malignancy incidences were found in these patients treated with hemodialysis or peritoneal dialysis.5 Among these, more transitional cell carcinoma (TCC) was noted in Taiwan.6 Lower urine flow washout effect with chronic bladder irritation, longterm and inappropriate use of Chinese herbal drugs, analgesics, and heavy metal intoxication have been proposed as contributors.7-9 Owing to the improvement of immunosuppressant therapy, kidney transplantation (KT) has become the superior Received 24 April 2014. Revision requested 5 May 2014. Accepted 3 July 2014. 1
Division of Nephrology, Chi Mei Medical Center, Tainan, Taiwan.
2
Department of Hospital and Health Care Administration, Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
3
Division of Medical Research, Chi Mei Medical Center, Tainan, Taiwan.
The authors declare no conflicts of interest. The study was partially supported by grant CMFHR10082 from the hospital and supported by ministry of science and technology, Taiwan with grant number: MOST 103-2314-B-384-001.
option for renal replacement therapy. Patients’ survival has been prolonged after KT, but life expectancy is still far worse than for the general population.10 However, post-organ transplantation was also associated with higher incidence of malignancy,11 with incidence rates of urologic malignancy post-KT varying across countries.11,12 Urologic malignancies, especially TCC, were found to be an important complication after KT in China,13 where its incidence was found to be even higher than other parts of the world. Compared to the male sex, female ESRD patients on dialysis were reported to have a higher risk of urologic malignancy.5 Does this sex difference diminish or increase after KT? No answer has been documented yet. Few studies, especially large-scale analyses, have compared the sex discrepancy of this malignancy incidence between ESRD patients and post-KT recipients. In this study with population-based data, we compared the sex disparity in urologic malignancy incidence in those ESRD patients receiving successful KT in Taiwan from 1999 to 2007. The benefit for long-term survival of these recipients after developing urologic malignancy was also evaluated because KT has been reported to have a better survival compared to dialysis for ESRD patients.14
J.-C.H. participated in research design and article writing. M.-Y.J. participated in reference search and part of article writing. Y.-H.L. participated in performance of the research. S.-F.W. participated in data analysis and statistics.
RESULTS
Correspondence: Jyh-Chang Hwang, M.D., 901 Zhonghua Rd., Yongkang Dist., Tainan City, 71010, Taiwan. ([email protected]).
Baseline Demographic Differences Among ESRD Patients With and Without KT
Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
As shown in Table 1, both KT and non-KT patients were age-matched and sex-matched. The transplant patients had similar percentages of diabetes mellitus (DM), hypertension,
ISSN: 0041-1337/15/9904-818 DOI: 10.1097/TP.0000000000000406
818
www.transplantjournal.com
Transplantation
■
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
April 2015
■
Volume 99
■
Number 4
Hwang et al
© 2014 Wolters Kluwer
819
TABLE 1.
Demographic characteristics and comorbid disorders between the patients receiving KT and those of non-KT uremic patients
Age at index date, yr Age at index date, n (%)
