Sirolimus is associated with new-onset diabetes in kidney transplant recipients

被引:317
作者
Johnston, Olwyn [1 ]
Rose, Caren L. [1 ]
Webster, Angela C. [2 ]
Gill, John S. [1 ]
机构
[1] Univ British Columbia, St Pauls Hosp, Div Nephrol, Vancouver, BC V6Z 1Y6, Canada
[2] Childrens Hosp Westmead, Natl Hlth & Med Res Council Ctr Clin Excellence R, Sydney, NSW, Australia
来源
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2008年 / 19卷 / 07期
关键词
D O I
10.1681/ASN.2007111202
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
New-onset diabetes (NOD) is associated with transplant failure. A few single-center studies have suggested that sirolimus is associated with NOD, but this is not well established. With the use of data from the United States Renal Data System, this study evaluated the association between sirolimus use at the time of transplantation and NOD among 20,124 adult recipients of a first kidney transplant without diabetes. Compared with patients treated with cyclosporine and either mycophenolate mofetil or azathioprine, sirolimus-treated patients were at increased risk for NOD, whether it was used in combination with cyclosporine (adjusted hazard ratio [HR] 1.61; 95% confidence interval [CI] 1.36 to 1.90), tacrolimus (adjusted HR 1.66; 95% CI 1.42 to 1.93), or an antimetabolite (mycophenolate mofetil or azathioprine; adjusted HR 1.36; 95% CI 1.09 to 1.69). Similar results were obtained in a subgroup analysis that included the 16,861 patients who did not have their immunosuppressive regimen changed throughout the first posttransplantation year. In conclusion, sirolimus is independently associated with NOD. Given the negative impact of NOD on posttransplantation outcomes, these findings should be confirmed in prospective studies or in meta-analyses of existing trials that involved sirolimus.
引用
收藏
页码:1411 / 1418
页数:8
相关论文
共 43 条
[21]   Tacrolimus versus cyclosporin for immunosuppression in renal transplantation: meta-analysis of randomised trials [J].
Knoll, GA ;
Bell, RC .
BRITISH MEDICAL JOURNAL, 1999, 318 (7191) :1104-1107
[22]   Benefit-risk assessment of sirolimus in renal transplantation [J].
Kuypers, DRJ .
DRUG SAFETY, 2005, 28 (02) :153-181
[23]   Glucose-stimulated DNA synthesis through mammalian target of rapamycin (mTOR) is regulated by KATP channels -: Effects on cell cycle progression in rodent islets [J].
Kwon, G ;
Marshall, CA ;
Liu, H ;
Pappan, KL ;
Remedi, MS ;
McDaniel, ML .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (06) :3261-3267
[24]   Disordered fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes [J].
Lewis, GF ;
Carpentier, A ;
Adeli, K ;
Giacca, A .
ENDOCRINE REVIEWS, 2002, 23 (02) :201-229
[25]   Multicenter randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of renal allograft rejection - A report of the European Tacrolimus Multicenter Renal Study Group [J].
Mayer, AD ;
Dmitrewski, J ;
Squifflet, JP ;
Besse, T ;
Grabensee, B ;
Klein, B ;
Eigler, FW ;
Heemann, U ;
Pichlmayr, R ;
Behrend, M ;
Vanrenterghem, Y ;
Donck, J ;
vanHooff, J ;
Christiaans, M ;
Morales, JM ;
Andres, A ;
Johnson, RWG ;
Short, C ;
Buchholz, B ;
Rehmert, N ;
Land, W ;
Schleibner, S ;
Forsythe, JLR ;
Talbot, D ;
Neumayer, HH ;
Hauser, I ;
Ericzon, BG ;
Brattstrom, C ;
Claesson, K ;
Muhlbacher, F ;
Pohanka, E .
TRANSPLANTATION, 1997, 64 (03) :436-443
[26]   Differences in diabetes prevalence, incidence, and mortality among the elderly of four racial/ethnic groups: Whites, blacks, Hispanics, and Asians [J].
McBean, AM ;
Li, SL ;
Gilbertson, DT ;
Collins, AJ .
DIABETES CARE, 2004, 27 (10) :2317-2324
[27]   A prospective, randomized trial of tacrolimus in combination with sirolimus or mycophenolate mofetil in kidney transplantation: Results at 1 year [J].
Mendez, R ;
Gonwa, T ;
Yang, HC ;
Weinstein, S ;
Jensik, S ;
Steinberg, S .
TRANSPLANTATION, 2005, 80 (03) :303-309
[28]   Diabetes mellitus after renal transplantation - As deleterious as non-transplant-associated diabetes? [J].
Miles, AMV ;
Sumrani, N ;
Horwitz, R ;
Homel, P ;
Maursky, V ;
Markell, MS ;
Distant, DA ;
Hong, JH ;
Sommer, BG ;
Friedman, EA .
TRANSPLANTATION, 1998, 65 (03) :380-384
[29]   Inhibition of lipolysis causes suppression of endogenous glucose production independent of changes in insulin [J].
Mittelman, SD ;
Bergman, RN .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2000, 279 (03) :E630-E637
[30]  
O'Connor PJ, 1998, AM J MANAG CARE, V4, P335