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Sirolimus Is Associated with New-Onset Diabetes in Kidney Transplant Recipients
Abstract
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 orazathioprine, 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 orazathioprine; 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.
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“Chronic treatment of humans with high doses of rapalogs is also associated with deleterious metabolic consequences including hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, insulin resistance and glucose intolerance 139–143.”
From Targeting the biology of aging with mTOR inhibitors (2023) · cites this paper as [141]
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Lamming, D. W., Ye, L., Katajisto, P., Goncalves, M. D., Saitoh, M., Stevens, D. M., Davis, J. G., Salmon, A. B., Richardson, A., Ahima, R. S., et al. (2012) · Science · doi:10.1126/science.1215135 · Cited by 1,199
Sharif, A., Hecking, M., de Vries, A. P. J., Porrini, E., Hornum, M., Rasoul-Rockenschaub, S., Berlakovich, G., Krebs, M., Kautzky-Willer, A., Schernthaner, G., et al. (2014) · American Journal of Transplantation · doi:10.1111/ajt.12850 · Cited by 532
“Johnston et al, analyzing data from the United States Renal Data System, found sirolimus were independently associated with increased risk for PTDM (38).”
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Mannick, J. B., & Lamming, D. W. (2023) · Nature Aging · doi:10.1038/s43587-023-00416-y · Cited by 372
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Albert, V., & Hall, M. N. (2015) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2014.12.001 · Cited by 304
Metadata
- Authors
- Johnston, O., Rose, C. L., Webster, A. C., & Gill, J. S.
- Venue
- Journal of the American Society of Nephrology
- Published
- 2008-07
- Volume
- 19
- Issue
- 7
- Pages
- 1411-1418
- ISSN
- 1046-6673
- Cited by
- 359
- References
- 0
- Language
- en
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- Johnston, O., Rose, C. L., Webster, A. C., & Gill, J. S. (2008). Sirolimus Is Associated with New-Onset Diabetes in Kidney Transplant Recipients. Journal of the American Society of Nephrology. https://doi.org/10.1681/asn.2007111202