Cancer and mTOR inhibitors in kidney transplantation recipients

被引:5
作者
Kao, Chih-Chin [1 ,2 ,3 ]
Liu, Jia-Sin [4 ]
Chang, Yu-Kang [5 ]
Lin, Ming-Huang [4 ]
Lin, Yen-Chung [1 ,2 ,3 ]
Chen, Hsi-Hsien [2 ,3 ]
Chang, Wei-Chiao [6 ,7 ]
Hsu, Chih-Cheng [4 ,8 ]
Wu, Mai-Szu [1 ,3 ,9 ]
机构
[1] Taipei Med Univ, Coll Med, Grad Inst Clin Med, Taipei, Taiwan
[2] Taipei Med Univ Hosp, Dept Internal Med, Div Nephrol, Taipei, Taiwan
[3] Taipei Med Univ, Sch Med, Dept Internal Med, Taipei, Taiwan
[4] Natl Hlth Res Inst, Inst Populat Hlth Sci, Div Geriatr & Gerontol, Zhunan, Taiwan
[5] Res TungsTaichung Metroharbor Hosp, Dept Med Res, Taichung, Taiwan
[6] Taipei Med Univ, Coll Med, Dept Clin Pharm, Taipei, Taiwan
[7] Taipei Med Univ, Sch Pharm, Master Program Clin Pharmacogen & Pharmacoprote, Taipei, Taiwan
[8] China Med Univ, Dept Hlth Serv Adm, Taichung, Taiwan
[9] Shuang Ho Hosp, Dept Internal Med, Div Nephrol, New Taipei, Taiwan
关键词
Chronic kidney disease; Cancer; Kidney transplantation; Mortality; mTOR inhibitors; REGULATORY T-CELLS; MAMMALIAN TARGET; CALCINEURIN-INHIBITOR; RENAL-TRANSPLANTATION; RAPAMYCIN INHIBITORS; SKIN-CANCER; SIROLIMUS; CYCLOSPORINE; MALIGNANCY; IMMUNOSUPPRESSION;
D O I
10.7717/peerj.5864
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background: Previous studies show that mTOR inhibitors decrease the risk of cancer development after kidney transplantation. However, the effect of cumulative doses of mTOR inhibitors on cancer after kidney transplantation is not well known. Methods: In the current study, patients were registered into a national database in Taiwan. Between year 2000 and 2013, 4,563 patients received kidney transplantation. They were divided into two groups, according to mTOR inhibitors usage. The cumulative dose of mTOR inhibitors was recorded. Patients were followed-up until de novo cancer development, death, or the end of 2014. Results: Patients were divided into two groups: mTOR inhibitors users (study group, n = 828) and mTOR inhibitors non-users (control group, n = 3,735). The median follow-up duration was 7.8 years. The risk of de novo cancer (hazards ratio (HR) 0.80, 95% CI [0.60-1.09], p = 0.16) and risk of death (HR 1.14, 95% CI [0.82-1.60], p = 0.43) was not different between mTOR inhibitor user and non-user groups. Neither high- nor low-dose exposure to mTOR inhibitors was associated with increased risk of cancer or mortality. Analysis of cancer subtypes showed no influence by mTOR inhibitors. In addition, the cause of mortality was not significantly different between the two groups. Discussion: We could not find the association of mTOR inhibitors use and risk of de novo cancer development or mortality in patients with kidney transplantation in Chinese patients. Cumulative exposure to mTOR inhibitors did not change the results.
引用
收藏
页数:19
相关论文
共 49 条
[1]   Lower Malignancy Rates in Renal Allograft Recipients Converted to Sirolimus-Based, Calcineurin Inhibitor-Free Immunotherapy: 24-Month Results From the CONVERT Trial [J].
Alberu, Josefina ;
Pascoe, Michael D. ;
Campistol, Josep M. ;
Schena, Francesco P. ;
del Carmen Rial, Maria ;
Polinsky, Martin ;
Neylan, John F. ;
Korth-Bradley, Joan ;
Goldberg-Alberts, Robert ;
Maller, Eric S. .
TRANSPLANTATION, 2011, 92 (03) :303-310
[2]  
[Anonymous], 2014, BMJ BRIT MED J, DOI DOI 10.1136/BMJ.G6679
[3]  
[Anonymous], 2014, Handbook of Biological Statistics Internet
[4]   VHL and HIF signalling in renal cell carcinogenesis [J].
Baldewijns, Marcella M. ;
van Vlodrop, Iris J. H. ;
Vermeulen, Peter B. ;
Soetekouw, Patricia M. M. B. ;
van Engeland, Manon ;
de Bruine, Adriaan P. .
JOURNAL OF PATHOLOGY, 2010, 221 (02) :125-138
[5]   Cancer risk in patients on dialysis and after renal transplantation [J].
Birkeland, SA ;
Lokkegaard, H ;
Storm, HH .
LANCET, 2000, 355 (9218) :1886-1887
[6]   Effect of maintenance immunosuppressive drugs on virus pathobiology: evidence and potential mechanisms [J].
Brennan, Daniel C. ;
Aguado, Jose M. ;
Potena, Luciano ;
Jardine, Alan G. ;
Legendre, Christophe ;
Saeemann, Marcus D. ;
Mueller, Nicolas J. ;
Merville, Pierre ;
Emery, Vincent ;
Nashan, Bjoern .
REVIEWS IN MEDICAL VIROLOGY, 2013, 23 (02) :97-125
[7]   Causes of death after renal transplantation [J].
Briggs, JD .
NEPHROLOGY DIALYSIS TRANSPLANTATION, 2001, 16 (08) :1545-1549
[8]   Five-Year Outcomes in Kidney Transplant Patients Converted From Cyclosporine to Everolimus: The Randomized ZEUS Study [J].
Budde, K. ;
Lehner, F. ;
Sommerer, C. ;
Reinke, P. ;
Arns, W. ;
Eisenberger, U. ;
Wuethrich, R. P. ;
Muehlfeld, A. ;
Heller, K. ;
Porstner, M. ;
Veit, J. ;
Paulus, E. -M. ;
Witzke, O. .
AMERICAN JOURNAL OF TRANSPLANTATION, 2015, 15 (01) :119-128
[9]   Randomized Controlled Trial of Sirolimus for Renal Transplant Recipients at High Risk for Nonmelanoma Skin Cancer [J].
Campbell, S. B. ;
Walker, R. ;
Tai, S. See ;
Jiang, Q. ;
Russ, G. R. .
AMERICAN JOURNAL OF TRANSPLANTATION, 2012, 12 (05) :1146-1156
[10]   Sirolimus therapy after early cyclosporine withdrawal reduces the risk for cancer in adult renal transplantation [J].
Campistol, Josep M. ;
Eris, Josette ;
Oberbauer, Rainer ;
Friend, Peter ;
Hutchison, Brian ;
Morales, Jose M. ;
Claesson, Kerstin ;
Stallone, Giovanni ;
Russ, Graeme ;
Rostaing, Lionel ;
Kreis, Henri ;
Burke, James T. ;
Brault, Yves ;
Scarola, Joseph A. ;
Neylan, John F. .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2006, 17 (02) :581-589