Everolimus With Reduced Calcineurin Inhibitor in Thoracic Transplant Recipients With Renal Dysfunction: A Multicenter, Randomized Trial

Gullestad, Lars; Iversen, Martin; Mortensen, Stefan P.; Eiskjær, Hans; Riise, Gerdt C.; Mared, L.; Bjørtuft, Øystein; Ekmehag, Björn; Jansson, Kjell; Simonsen, Svein; Gude, Einar; Rundqvist, Bengt; Fagertun, H.; Solbu, D.; Bergh, Claes‐Håkan

doi:10.1097/tp.0b013e3181cbac2d

Cited by 135 publications

(125 citation statements)

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“…The mean baseline measured GFR was close to 50 mL/ min. There was a significant improvement of renal function at one and two years [44,45]. After 2 years, the measured GFR improved by 3.2 mL/min on EVRL and decreased by 2.4 mL/min in controls.…”

mentioning

confidence: 74%

“…After 2 years, the measured GFR improved by 3.2 mL/min on EVRL and decreased by 2.4 mL/min in controls. Shorter time from transplantation to enrollment was predictive of response, so that OHT patients enrolled more than 8 years after transplantation had no benefit from CNI reduction [44]. EVRL was associated with twice as many pneumonias in the first year and 1.8 fold increases in risk of rejection after 2 years.…”

Section: Reduction Of Cnis Dosementioning

confidence: 98%

“…Most of them were followed for up to 2 years [44,45]. Everolimus (EVRL) was added and the dose of CNI was reduced by close to 60%.…”

Section: Reduction Of Cnis Dosementioning

confidence: 99%

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Cardiac Troponin I Level in STEMI and Clinical Correlation with Left Ventricular Dysfunction in Indian Population

Sharma¹,

Sharma²

2013

J Cardiovasc Dis Diagn

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Calcium Channel Blockers (CCBs): CNIs cause vasoconstriction as noted above. CCBs, specifically vasodilating dihydropyridines, have been shown to improve renal plasma flow and GFR [9,16]. A small prospective study comparing amlodipine to placebo showed a slower decline in GFR at one year [13]. There was no effect on LV mass and only a modest decrease in proteinuria. Diltiazem did not appear to offer the same protection [14]. RAAS Inhibitors:The use of RAAS inhibitors is beneficial in most patients with CKD; however, this has not been shown in OHT patients. A systematic review of randomized studies in CSA-treated kidney AbstractBackground: The use of calcineurin inhibitors revolutionized transplantation by prolonging patients' survival. However, their utility is limited by the development of significant chronic kidney disease. Methods:We reviewed the English literature looking for recent publications regarding the management of chronic kidney disease in cardiac transplant patients. We chose relevant papers based on design, number of patients and clinical utility.Results: Most publications on the subject involve small populations with few prospective, randomized studies. Early use of tacrolimus appears to be associated with better kidney function after one year compared to cyclosporine. Once chronic kidney disease is established, successful strategies include reduction or elimination of calcineurin inhibitors while relying on mycophenolate mofetil, proliferation signal inhibitors or anti-CD 25 antibodies to prevent rejection. There is no follow up longer than two years with these approaches. Kidney transplantation might offer improved long-term survival compared to dialysis in end-stage disease. Conclusions:Prospective studies with long-term follow-up are needed to decide about the timing and to confirm the utility of replacing calcineurin inhibitors with other agents in cardiac transplant patients with chronic kidney disease. transplant patients show, after a median of 27 months, a reduction in GFR (around 5.8 cc/min) with a reduction of proteinuria (decrease of 470 mg/day) [17]. It is uncertain if the reduction in proteinuria would translate into better outcomes in the long run. In fact, Opelz et al. showed, in a retrospective study of 1,744 OHT patients, that the use of RAAS inhibitors did not improve patient survival after 6 years [18]. The same study looked at 17,209 kidney transplant patients and showed no difference in graft or patient survival [18]. The use of spironolactone in rat models prevented the decline in GFR and the histologic changes seen with CSA [19]. There are no data in patients. Management of Calcineurin Modification of immunosuppressive drugsTransplant centers have tried multiple immunosuppressive strategies in OHT patient with CKD to prevent progression of renal dysfunction. Most of the data come from small studies, limiting the strength of recommendations that can be made. Larger studies come usually from kidney transplantation literature. Tacrolimus:In small studies, Tacrolimus (TAC) do...

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mentioning

confidence: 74%

Section: Reduction Of Cnis Dosementioning

confidence: 98%

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Cardiac Troponin I Level in STEMI and Clinical Correlation with Left Ventricular Dysfunction in Indian Population

Sharma¹,

Sharma²

2013

J Cardiovasc Dis Diagn

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“…13) CNI-minimization or free regimens plus EVL have advantages in terms of the improvement of renal function among heart or renal transplantation recipients, and EVL-incorporated regimens have recently been increasing. [16][17][18][19][20] Recent clinical studies including ours also demonstrated the suppressive effects of EVL in cardiac allograft vasculopathy and post-transplant malignancy. [21][22][23][24][25] Considering that both SRL and EVL are mTOR inhibitors, EVL may also have a repressive effect on LVM.…”

Section: Eft Ventricular Hypertrophy (Lvh) Is Observed In Pa-mentioning

confidence: 99%

Everolimus Attenuates Myocardial Hypertrophy and Improves Diastolic Function in Heart Transplant Recipients

et al. 2016

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SummaryEverolimus (EVL), one of the mammalian targets of rapamycin, is a next generation immunosuppressant that may have accessory anti-proliferative effects in heart transplant (HTx) recipients. However, little is known about the clinical relationship between EVL and regression of cardiac hypertrophy. A total of 42 HTx recipients received EVL therapy at post-HTx 150 days on median and had been followed at our institute for > 1 year between 2008 and 2014 [EVL (+) group]. We also observed 18 patients without EVL from post-HTx 150 days for 1 year [EVL (-) group]. There were no significant differences in baseline variables between the two groups. Left ventricular mass index (LVMI) and the ratio of early transmitral filling velocity to the peak early diastolic mitral annular motion velocity (E/e') decreased significantly during 1-year EVL treatment compared with the EVL (-) group. There were no differences in blood pressure and medications between the 2 groups. Improvement of LVMI and the E/e' ratio was not associated with trough levels of calcineurin inhibitors or EVL, but correlated with each baseline value. In conclusion, this EVL-incorporated immunosuppressant regimen attenuated cardiac hypertrophy as well as diastolic dysfunction in HTx recipients. (Int Heart J 2016; 57: 204-210)

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“…This results in reduced production of interleukin 2, inhibiting T-cell proliferation. 15,16 According to the Kidney Disease Improving Global Outcomes 2009 clinical practice guidelines, the combination of tacrolimus with an antiproliferative agent, with or without corticosteroids, is the most favored first-line CNI for initial maintenance therapy. Thus, tacrolimusbased regimens are the most commonly used regimens, with 80% of initial immuno suppression and 70% of maintenance immunosup pression received by renal transplant recipients.…”

Section: Introductionmentioning

confidence: 99%

Untitled

Jayant

Bridson

Sharma³

et al. 2017

Exp Clin Transplant

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Objectives: This review focuses on the current limited evidence of graft function and graft survival in various immunosuppressive regimens involving mammalian target of rapamycin inhibitors with or without calcineurin inhibitors. Materials and Methods: We evaluated the current literature for describing the role of mammalian target of rapamycin inhibitors as an alternative to calcineurin inhibitors by searching the PubMed, EMBASE, Cochrane, Crossref, and Scopus databases using medical subject heading terms. Results: Our detailed analyses of all relevant literature showed use of mammalian target of rapamycin inhibitor-based de novo regimens, early calcineurin inhibitor withdrawal with subsequent introduction of mammalian target of rapamycin inhibitor-based regimens, and late conversion from a calcineurin inhibitor-based regimen to mammalian target of rapamycin inhibitor-based regimens. Notably, early calcineurin inhibitor withdrawal with subsequent introduction of mammalian target of rapamycin inhibitor-based regimen seemed to be a more practical and realistic approach toward immunosuppressive treatment of renal transplant recipients. However, in view of the high rejection rate observed in these studies, it is advisable not to offer these regimens to patients with moderate to high immunologic risk. Conclusions: The present evidences suggest that treatment with mammalian target of rapamycin inhibitors allows early and substantial calcineurin inhibitor minimization. The mammalian target of rapamycin inhibitors everolimus and sirolimus are preferred due to their complementary mechanisms of action and favorable nephrotoxicity profile, which have opened the way for calcineurin inhibitor reduction/withdrawal in the early posttransplant period.

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Everolimus With Reduced Calcineurin Inhibitor in Thoracic Transplant Recipients With Renal Dysfunction: A Multicenter, Randomized Trial

Abstract: Introduction of everolimus with CNI reduction offers a significant improvement in renal function in maintenance heart and lung transplant recipients. The greatest benefit is observed in patients with a shorter time since transplantation.

Cited by 135 publications

References 33 publications

Cardiac Troponin I Level in STEMI and Clinical Correlation with Left Ventricular Dysfunction in Indian Population

Cardiac Troponin I Level in STEMI and Clinical Correlation with Left Ventricular Dysfunction in Indian Population

Everolimus Attenuates Myocardial Hypertrophy and Improves Diastolic Function in Heart Transplant Recipients

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