Long‐term outcome after early cyclosporine withdrawal in kidney transplantation: ten years after

Tabibzadeh, Nahid; Glowacki, François; Frimat, Marie; Elsermans, Vincent; François, Patrice; Lionet, Arnaud; Gnemmi, Viviane; Hertig, Alexandre; Noël, Christian; Hazzan, Marc

doi:10.1111/ctr.12843

Cited by 6 publications

(6 citation statements)

References 35 publications

(65 reference statements)

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“…In the late‐stage setting, patients with poor renal function have been shown to experience limited benefit from mTORi conversion, due to an increased incidence of adverse events . CNI withdrawal without replacement is generally not a valuable option . CNI minimization, as was performed here in the control group, has not proven strong evidence of graft function improvement, while it can increase the risk of de novo DSA appearance and chronic humoral rejection .…”

Section: Discussionmentioning

confidence: 95%

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Belatacept Rescue Therapy in Kidney Transplant Recipients With Vascular Lesions: A Case Control Study

Bertrand¹,

Cheddani²,

Étienne³

et al. 2017

American Journal of Transplantation

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Immunosuppression in kidney transplant recipients with decreased graft function and severe histological vascular changes can be particularly challenging. Belatacept could be a valuable option, as a rescue therapy in this context. We report a retrospective case control study comparing a CNI to belatacept switch in 17 patients with vascular damage and low eGFR to a control group of 18 matched patients with CNI continuation. Belatacept switch was performed on average 51.5 months after kidney transplantation (6.2-198 months). There was no difference between the two groups regarding eGFR at inclusion, and 3 months before inclusion. In the "CNI to belatacept switch group," mean eGFR increased significantly from 23.5 ± 6.7 mL/min/1.73m on day 0, to 30.4 ± 9.1 mL/min/1.73 m on month 6 (p < 0.001) compared to the control group, in which no improvement was observed. These results were still significant on month 12. Two patients experienced biopsy-proven acute rejection. One was effectively treated without belatacept discontinuation. Two patients needed belatacept discontinuation for infection. In conclusion, the remplacement of CNI with belatacept in patients with decreased allograft function and vascular lesions is associated with an improvement in eGFR.

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Section: Discussionmentioning

confidence: 95%

“…The inclusion of calcineurin inhibitors (CNI) in immunosuppressant regimens has significantly improved early kidney allograft survival . Paradoxically, strategies based on CNI have not been associated with an improvement in long‐term graft survival.…”

Section: Introductionmentioning

confidence: 99%

Belatacept Rescue Therapy in Kidney Transplant Recipients With Vascular Lesions: A Case Control Study

Bertrand¹,

Cheddani²,

Étienne³

et al. 2017

American Journal of Transplantation

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“…19 Similar results were reported in a recent retrospective multicenter European study, that showed a lower incidence of de novo DSA in BTC-treated kidney transplants. 21 Furthermore, BTC cannot be considered to be responsible for DSA, which was absent after 1 dose in the highly sensitized patient, considering the desensitization protocol administered prior to transplantation. CSA discontinuation is associated with an increased incidence of Class II DSA.…”

Section: Discussionmentioning

confidence: 99%

“…CSA discontinuation is associated with an increased incidence of Class II DSA. 21 Furthermore, BTC cannot be considered to be responsible for DSA, which was absent after 1 dose in the highly sensitized patient, considering the desensitization protocol administered prior to transplantation.…”

Section: Discussionmentioning

confidence: 99%

Belatacept-based immunosuppression: A calcineurin inhibitor-sparing regimen in heart transplant recipients

Launay

Guitard

Dorent

et al. 2020

American Journal of Transplantation

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| INTRODUC TI ONCalcineurin inhibitors (CNI) are the backbone of immunosuppression in solid organ transplantation, but long-term exposure is often associated with nephrotoxicity. 1 Belatacept (BTC) (Nulojix ® ) is a highaffinity CTLA4Ig indicated for the prophylaxis of graft rejection in adults receiving a renal transplant in combination with mycophenolic acid (MPA) and corticosteroids. 2,3 The BENEFIT study demonstrated that BTC-based regimens were associated with a similar incidence of acute rejection but improved renal function compared to a cyclosporine-based regimen in renal transplant recipients. 4 The BENEFIT and BENEFIT-EXT studies showed that the risk of posttransplant

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“…However, renal transplantation may exert beneficial effects on aortic stiffness evolution through kidney function recovery [ 15 ]. Conversely, new-onset diabetes, hypertension and/or dyslipidemia may occur following renal grafting, due to immunosuppressive drug side effects [ 16 , 17 ]. Moreover, calcineurin inhibitors (CNI), which remain a cornerstone treatment in renal transplant patients, induce a renal and systemic vasoconstrictive effect leading to increased peripheral wave reflection [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

From arterial stiffness to kidney graft microvasculature: Mortality and graft survival within a cohort of 220 kidney transplant recipients

et al. 2018

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BackgroundAortic stiffness assessed by carotid-femoral pulse wave velocity (CF-PWV) is a predictor of mortality in several populations. However, little is known in kidney transplant recipients. Our objectives were to evaluate the ability of CF-PWV measured 3 months following transplantation to predict mortality, graft loss and its potential links to measured Glomerular Filtration Rate (mGFR) or kidney graft microvasculature parameters.MethodsThe study is based on a monocentric retrospective cohort including 220 adult kidney graft recipients evaluated three months after transplantation. CF-PWV measures, clinical, laboratory and histological data performed at 3 (M3) and 12 months (M12) following transplantation were retrospectively collected. The two primary endpoints were all-cause mortality and occurrence of end stage renal disease (ESRD) defined by initiation of dialysis.ResultsAfter a median follow up of 5.5 years [1.9; 8.8], death and graft loss occurred in 10 and 12 patients respectively. M3 CF-PWV was an independent mortality risk factor (HR = 1.29 [1.03; 1.61]; p = 0.03), despite no aortic stiffness variation during the first year of transplantation. Of notice, M3 CF-PWV was not associated with M12 mGFR or ESRD outcome. Graft microcirculation assessed by Banff vascular fibrous intimal thickening score (cv) worsened between M3 and M12 (p = 0.01), but no link was found with CF-PWV, mGFR or ESRD outcome. Surprisingly, acute rejections at M3 were associated after adjustment with mortality (p = 0.03) but not ESRD.ConclusionAortic stiffness measured 3 months after kidney transplantation is a strong predictor of mortality with no obvious influence on kidney graft microvasculature or graft loss.

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Long‐term outcome after early cyclosporine withdrawal in kidney transplantation: ten years after

Abstract: MMF withdrawal largely failed due to CNI toxicity, while CsA withdrawal led to increased graft failure due to uncontrolled acute rejection without increasing graft survival. From this study, it remains unclear which patients could benefit from limiting CNI exposure.

Cited by 6 publications

References 35 publications

Belatacept Rescue Therapy in Kidney Transplant Recipients With Vascular Lesions: A Case Control Study

Belatacept Rescue Therapy in Kidney Transplant Recipients With Vascular Lesions: A Case Control Study

Belatacept-based immunosuppression: A calcineurin inhibitor-sparing regimen in heart transplant recipients

From arterial stiffness to kidney graft microvasculature: Mortality and graft survival within a cohort of 220 kidney transplant recipients

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