Sirolimus and Kidney Transplantation: Unraveling an Inflammatory Affair

Weichhart, Thomas; Säemann, Marcus D.

doi:10.1111/j.1600-6143.2010.03306.x

Cited by 3 publications

(1 citation statement)

References 5 publications

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“…It is possible that sirolimus exerts a differential effect on the risk of recurrence depending on the type of glomerulopathy, but its mechanism remains unclear. Recent data suggest that sirolimus may have a paradoxical proinflammatory effect and that this could be responsible for the apparent increased risk of IgAN in sirolimus‐treated patients. Further studies are required to specifically look into the mechanistic reason for our observation.…”

Section: Discussionmentioning

confidence: 99%

The risk of recurrent IgA nephropathy in a steroid‐free protocol and other modifying immunosuppression

Visger

Günay

Andreoni

et al. 2014

Clinical Transplantation

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Recurrent glomerulonephritis is an important cause of kidney allograft failure. The effect of immunosuppression on recurrent IgA nephropathy (IgAN) is unclear. We analyzed the impact of steroids and other immunosuppression on the risk of recurrent IgAN post-kidney transplantation. Between June 1989 and November 2008, 3311 kidney transplants were performed at our center. IgAN was the primary disease in 124 patients; of these, 75 (60.5%) patients received steroid-based immunosuppression (15 undergoing late steroid withdrawal), and 49 (39.5%) were maintained on steroid-free immunosuppression. Recurrent IgAN was diagnosed in 27 of 124 (22%) patients in clinically indicated kidney allograft biopsies over a median follow-up of 6.86 ± 5.4 yr. On cox proportional hazards model multivariate analysis, the hazard risk (HR) of IgAN recurrence was significantly higher in patients managed with steroid-free (HR 8.59: 3.03, 24.38, p < 0.001) and sirolimus-based (HR = 3.00:1.16, 7.75, p = 0.024) immunosuppression without antilymphocyte globulin induction (HR = 4.5: 1.77, 11.73, p = 0.002). Mycophenolate use was associated with a lower risk (HR = 0.42: 0.19, 0.95, p = 0.036), whereas cyclosporine did not have a significant impact on the risk of IgAN recurrence (p = 0.61). These results warrant future prospective studies regarding the role of steroids and other immunosuppression drugs in reducing recurrence of IgAN and other glomerulonephritis post-transplant.

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Section: Discussionmentioning

confidence: 99%

The risk of recurrent IgA nephropathy in a steroid‐free protocol and other modifying immunosuppression

Visger

Günay

Andreoni

et al. 2014

Clinical Transplantation

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Rapamune Does Not Attenuate High Cholesterol-Induced Atherosclerosis in Rabbits

Attia

Ahmed

et al. 2014

Int J Angiol

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Solid-organ transplant recipients are prone to develop atherosclerosis. The objectives of this study were to investigate the effects of Rapamune (Wyeth Canada, Saint-Larent, QC, Canada) on the rabbit model of atherosclerosis. The rabbits were assigned to four groups: group I, regular diet (control); group II, 1% cholesterol diet; group III, control with Rapamune (1 mg/kg/d orally); and group IV, high cholesterol diet with Rapamune. Blood samples for serum lipids (triglycerides [TG], total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C]), as well as malondialdehyde, and protein carbonyls, the indices of oxidative stress were collected at the end of 2 months on the respective diet regimen. Aortic tissue for atherosclerotic changes were also collected for oxidative stress indices were also collected. Rapamune reduced serum levels of TG, TC, LDL-C, and HDL-C. Rapamune elevated the oxidative stress in rabbits on high cholesterol diet. Rapamune did not attenuate extent of atherosclerosis (group II vs. group IV, 45.00???12.00 vs. 57.28???2.99%); intimal thickness (group II vs. group IV, 32.38???7.14???103 vs. 21.90???11.98???103 ?m2); intimal/medial ratio (group II vs. group IV, 0.50???0.06 vs. 0.35???0.06); and macrophage accumulation (group II vs. group IV, 69.72???5.02 vs. 61.52???8.94%) in the intima of rabbits on high cholesterol diet. The data suggest that (1) Rapamune increased the oxidative stress in rabbits on high cholesterol diet and (2) Rapamune did not attenuate the hypercholesterolemic atherosclerosis in the rabbit model.

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An evaluation of sirolimus in renal transplantation

Halleck¹,

Duerr²,

Waiser³

et al. 2012

Expert Opinion on Drug Metabolism & Toxicology

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Sirolimus enriches the possibilities of immunosuppressive therapies after renal transplantation. Beneficial effects toward kidney function by allowing CNI sparing, lower incidence of malignancies and less viral infections have been suggested. Sirolimus should be used cautiously in de novo patients for reasons of wound healing. An early conversion to a sirolimus-based CNI-free regimen has shown promising results, whereas late conversion is more challenging. Finally, sirolimus-associated side effects are causing tolerability concerns and frequent discontinuations. Future research should aim to better define the therapeutic window and those patients most likely to benefit.

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Sirolimus and Kidney Transplantation: Unraveling an Inflammatory Affair

Cited by 3 publications

References 5 publications

The risk of recurrent IgA nephropathy in a steroid‐free protocol and other modifying immunosuppression

The risk of recurrent IgA nephropathy in a steroid‐free protocol and other modifying immunosuppression

Rapamune Does Not Attenuate High Cholesterol-Induced Atherosclerosis in Rabbits

An evaluation of sirolimus in renal transplantation

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