Incidence of Posttransplant Diabetes Mellitus in Kidney Transplant Recipients Immunosuppressed With Sirolimus in Combination With Cyclosporine

Romagnoli, Jacopo; Citterio, Franco; Nanni, Giuseppe; Favi, Evaldo; Tondolo, Vincenzo; Spagnoletti, Gionata; Salerno, Maria Paola; Castagneto, Marco

doi:10.1016/j.transproceed.2006.03.072

Cited by 43 publications

(27 citation statements)

References 5 publications

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“…De- spite lower tacrolimus levels in the black patients, the incidence of NOD in the black patients was 36 compared with 15% in white patients (P ϭ 0.02). In a retrospective study to examine the incidence of NOD among 86 consecutive renal transplant recipients in a single center between 1997 and 2004, Romagnoli et al 20 reported that patients treated with the combination of sirolimus and CsA had a significantly higher incidence of NOD compared with patients treated with CsA alone. Teutonico et al 21 demonstrated that chronic inhibition of mammalian target of rapamycin (mTOR) caused an increase in peripheral insulin resistance, along with impaired pancreatic ␤ cell response to a glucose load, in a cohort of 26 renal transplant recipients who were converted from treatment with CsA to sirolimus.…”

Section: Clinical Epidemiology Wwwjasnorgmentioning

confidence: 99%

“…19 Single-center studies have suggested that sirolimus may also be diabetogenic. 20,21 There are a number of possible mechanisms by which sirolimus may cause NOD, including impaired insulin-mediated suppression of hepatic glucose production, 22 insulin resistance from ectopic triglyceride deposition, 23,24 or direct ␤ cell toxicity. 25,26 Although multicenter trials using sirolimus failed to demonstrate an association between sirolimus and NOD, [27][28][29] patients in the comparator groups in these studies received corticosteroids and CNI; therefore, an independent association between sirolimus and NOD may not have been evident despite the relatively large number of participants in these trials.…”

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confidence: 99%

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Sirolimus Is Associated with New-Onset Diabetes in Kidney Transplant Recipients

Johnston

Rose

Webster

et al. 2008

Journal of the American Society of Nephrology

380

238

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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.

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Section: Clinical Epidemiology Wwwjasnorgmentioning

confidence: 99%

mentioning

confidence: 99%

Sirolimus Is Associated with New-Onset Diabetes in Kidney Transplant Recipients

Johnston

Rose

Webster

et al. 2008

Journal of the American Society of Nephrology

380

238

View full text Add to dashboard Cite

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“…Sirolimus does not have a marked effect on glucose metabolism, but a decrease in insulin sensitivity has been reported (116), as well as a worsening of glucose tolerance when sirolimus is added to a calcineurin-based protocol (117). Again, caution is advised in considering modifying immunosuppression to improve glucose tolerance because of the risk for rejection.…”

Section: Role Of Immunosuppressive Agentsmentioning

confidence: 99%

Management of Cardiovascular Disease in Renal Transplant Recipients

Shirali¹,

Bia²

2008

Clinical Journal of the American Society of Nephrology

110

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Cardiovascular disease is a major cause of graft loss and the leading cause of death in renal transplant recipients. Although there are robust data on the frequency of risk factors and their contributions to cardiovascular disease in this population, few trials have demonstrated the benefit of modifying these risk factors to reduce cardiovascular events. Nevertheless, it is widely accepted that the clinical acumen filtered through the best available studies in the general population be used to treat individual renal transplant recipients given their high cardiovascular mortality. Transplant task forces and the Kidney Disease Outcomes Quality Initiative have created guidelines for this purpose. This review examines the data available for prevention and treatment of major risk factors contributing to cardiovascular disease in renal transplant recipients. The contribution of immunosuppressive agents to each risk factor and the evidence to support lifestyle modification as well as drug therapy are examined. Reducing cardiovascular risk factors requires an integrative approach that is best accomplished by a team of health care professionals. It creates a significant challenge but one that must be met if allograft survival is to improve.

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“…The mammalian target of rapamycin is a widely expressed cellular kinase and is a critical mediator of cytokineinduced lymphocyte proliferation (80). Sirolimus is a potent immunosuppressant that inhibits mammalian target of rapamycin and also seems to be diabetogenic (81,82). This is supported by the fact that (1) in initial studies that compared CsA and sirolimus, NODM rates were not reduced in sirolimustreated patients (83,84); (2) combination CsA and sirolimus has been associated with more NODM than CsA alone (82); and (3) decreases in insulin sensitivity, pancreatic ␤ cell function, and overall glucose tolerance have been demonstrated, either after conversion from CsA to sirolimus or after tacrolimus elimination from a combined tacrolimus/sirolimus regimen (81).…”

Section: Immunosuppression and Tahmentioning

confidence: 99%

Transplant-Associated Hyperglycemia

Crutchlow¹,

Bloom²

2007

Clinical Journal of the American Society of Nephrology

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New-onset diabetes has long been recognized as a common complication of kidney transplantation, promoting cardiovascular disease, death, and graft failure. Studies in recent years have begun to highlight the very high posttransplantation prevalence of the prediabetic states of impaired fasting glucose and impaired glucose tolerance and the significant repercussions of these states on cardiovascular health. Therefore, the overall burden of transplant-associated hyperglycemia (TAH), which encompasses new-onset diabetes and the prediabetic states, is far greater than previously appreciated. The kidney transplant population is predisposed to insulin resistance and to additional insults of hypertension and hyperlipidemia that, together with hyperglycemia, compose the metabolic syndrome and promote atherosclerosis. When recipients with an underlying, frequently nonmodifiable predisposition to glucose dysregulation encounter transplant-specific, often modifiable, diabetogenic exposures, TAH manifests. Aggressive screening will effectively detect TAH, whereas risk factor modification, lifestyle intervention, and, when appropriate, drug therapy may decrease its impact. Topics of future investigation should include the use of emerging diabetes therapies and avenues for the prevention and reversal of TAH.

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Incidence of Posttransplant Diabetes Mellitus in Kidney Transplant Recipients Immunosuppressed With Sirolimus in Combination With Cyclosporine

Cited by 43 publications

References 5 publications

Sirolimus Is Associated with New-Onset Diabetes in Kidney Transplant Recipients

Sirolimus Is Associated with New-Onset Diabetes in Kidney Transplant Recipients

Management of Cardiovascular Disease in Renal Transplant Recipients

Transplant-Associated Hyperglycemia

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