Conversion to Everolimus in Kidney Transplant Recipients With Decreased Renal Function

Inza, A.; Balda, Sagrario; Álvarez, Eva; Zárraga, Sofía; Gaínza, Francisco J.; Lampreabe, I

doi:10.1016/j.transproceed.2009.05.013

Cited by 8 publications

(6 citation statements)

References 10 publications

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“…Although multiple reports exist on the association of sirolimus ‐treatment with an increased incidence of proteinuria , only few data are available on everolimus . As it is logical to assume that both mTOR inhibitors could exert the same effect on proteinuria, this observation might be explained by the longer use of sirolimus in renal transplantation.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, it can induce morphological changes in the cytoskeleton of human immortalized podocytes, which can result in proteinuria and morphological alterations such as foot process effacement . Only few reports were published on the effects of everolimus on proteinuria . Successful conversion from cyclosporine to everolimus has been described, although a slight increase in proteinuria was noted .…”

mentioning

confidence: 99%

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Cyclosporine versus everolimus: effects on the glomerulus

Baas

Kers

Florquin

et al. 2013

Clinical Transplantation

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Inhibitors of the mammalian target of rapamycin (mTOR) have been associated with proteinuria. We studied the development of proteinuria in renal transplant recipients (RTR) treated with the mTOR inhibitor everolimus in comparison with a calcineurin inhibitor. We related the presence of proteinuria to histopathological glomerular findings in two-yr protocol biopsies. In a single-center study, nested in a multicenter randomized controlled trial, we determined eGFR, proteinuria, and renal biopsy data (light- and electron microscopy) of RTR receiving prednisolone/everolimus (P/EVL) (n = 16) in comparison with patients treated with prednisolone/cyclosporine A (P/CsA) (n = 7). All patients had been on the above-described maintenance immunosuppression for 18 months. Renal function at two yr after transplantation did not differ between patients receiving P/EVL or P/CsA (eGFR 45.5 vs. 45.7 mL/min/1.73 m(2)). Proteinuria was slightly increased in P/EVL vs. P/CsA group (0.29 vs. 0.14 g/24 h, p = 0.06). There were no differences in light- or electron microscopic findings. We could not demonstrate increased podocyte effacement or changes in glomerular basement membrane (GBM) thickness in P/EVL-treated patients. In conclusion, long-term treatment with everolimus leaves the GBM and podocytes unaffected.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Cyclosporine versus everolimus: effects on the glomerulus

Baas

Kers

Florquin

et al. 2013

Clinical Transplantation

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“…The literature includes a number of single-center reports from small series of maintenance kidney transplant patients who were switched from CNI therapy to everolimus in response to declining renal function [45,46], malignant neoplasms or nonmelanoma skin cancer [47][48][49][50] or, more frequently, a mixture of indications but primarily renal deterioration or malignancy [51][52][53][54]. Studies of cohorts switched due to renal causes or for mixed reasons have consistently shown a significant improvement in renal function over follow-up periods ranging from six months to two years [45,46,[51][52][53][54].…”

Section: Everolimus As Rescue Therapymentioning

confidence: 99%

“…Studies of cohorts switched due to renal causes or for mixed reasons have consistently shown a significant improvement in renal function over follow-up periods ranging from six months to two years [45,46,[51][52][53][54].…”

Section: Everolimus As Rescue Therapymentioning

confidence: 99%

Everolimus immunosuppression in kidney transplantation: What is the optimal strategy?

Witzke

Sommerer

Arns

2016

Transplantation Reviews

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“…While dyslipidemia was observed in the majority of studies, proteinuria was not consistently observed. [73][74][75][76][77][78][79][80] A retrospective review of registry data for 272 patients followed for six months after introduction of everolimus was reported after approval of everolimus in Europe in 2005. Everolimus was preferentially introduced as a conversion strategy (93.8%) after the first month of transplantation.…”

Section: Preservation Of Allograft Functionmentioning

confidence: 99%

Impact of everolimus: update on immunosuppressive therapy strategies and patient outcomes after renal transplantation

Tedesco‐Silva¹,

Felipe²,

Freitas³

et al. 2011

TRRM

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Everolimus is an immunosuppressive agent used for the prophylaxis of acute rejection after kidney transplantation. Everolimus inhibits the activity of the serine/threonine kinase mammalian target of rapamycin (mTOR), a key enzyme that controls cell growth and metabolism, producing cell cycle arrest from the G1 to S phase. As a consequence, everolimus has antiproliferative and antineoplastic effects. Everolimus is a drug with a narrow therapeutic index. The pharmacokinetics of everolimus indicates a need for twice-daily dosing. Intra-and interindividual variability and drug-drug interactions suggest the need for therapeutic drug monitoring to maximize the efficacy/toxicity ratio. The good correlation between exposure (area under the concentration-time curve) and trough concentration indicates that monitoring of everolimus trough concentrations is an adequate strategy after kidney transplantation. Everolimus is indicated for low-to moderate-risk de novo kidney transplant candidates. There are no conclusive studies thus far indicating that everolimus can be used in high-risk patients, such as sensitized patients, retransplants, and African Americans. In de novo kidney transplant recipients, the recommended initial dose of everolimus is 0.75 mg twice daily, adjusted to maintain blood trough concentrations of 3-8 ng/mL, in combination with progressive reduction in blood trough cyclosporine concentrations to 25-50 ng/mL. In combination with reduced trough blood tacrolimus concentrations of 4-7 ng/mL the recommended initial dose of everolimus is 1.5 mg twice daily, adjusted to maintain trough blood concentrations of 3-8 ng/mL. Everolimus can also be used as a conversion strategy, mainly to preserve renal function and to manage patients with malignancy. There is no definition of the ideal strategy for conversion, ie, abrupt or sequential, initial dose of everolimus, or target therapeutic trough blood concentrations. Intensive monitoring is recommended after conversion, especially for acute rejection and proteinuria. Because mTOR is ubiquitous and central to many intracellular processes, an array of adverse reactions may occur, including delayed tissue regeneration, proteinuria, dyslipidemia, diabetes, myelosuppression, infertility, ovarian cysts, and mouth ulcers. Because long-term benefits are the goal of any immunosuppressive strategy, further investigations aiming to understand, prevent, and manage everolimus-related adverse reactions are necessary to mitigate the risks and improve tolerability, allowing maximization of all the benefits of this drug.

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Conversion to Everolimus in Kidney Transplant Recipients With Decreased Renal Function

Cited by 8 publications

References 10 publications

Cyclosporine versus everolimus: effects on the glomerulus

Cyclosporine versus everolimus: effects on the glomerulus

Everolimus immunosuppression in kidney transplantation: What is the optimal strategy?

Impact of everolimus: update on immunosuppressive therapy strategies and patient outcomes after renal transplantation

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