Long-Term Kidney Allograft Function and Survival in Prednisone-Free Regimens

Chhabra, Darshika; Skaro, Anton I.; Leventhal, Joseph R.; Dalal, Pranav; Shah, Gaurav; Wang, Edward; Gallon, Lorenzo

doi:10.2215/cjn.06940711

Cited by 45 publications

(32 citation statements)

References 44 publications

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“…Also combined reduced CNI + sirolimus or everolimus regimens have proven their efficacy and safety in a large number of studies. Besides improved preservation of renal function, reported rates of viral infections and malignancy are low compared with traditional CNI regimens [6][7][8][9][10][11]. However, the wider introduction of these agents has been limited by serious adverse effects and relatively high discontinuation rates [12].…”

Section: Introductionmentioning

confidence: 99%

Sirolimus and everolimus in kidney transplantation

Moes

Guchelaar

Fijter

2015

Drug Discovery Today

112

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Section: Introductionmentioning

confidence: 99%

Sirolimus and everolimus in kidney transplantation

Moes

Guchelaar

Fijter

2015

Drug Discovery Today

112

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“…[22][23][24] Still, in another study comparing tacrolimus-sirolimus with tacrolimus-mycophenolate mofetil over 8.5 years (tacrolimus concentrations were 8-10 ng/mL during the first 3 months), long-term renal graft survival and function were significantly worse in the tacrolimussirolimus group than in the tacrolimus-mycophenolate mofetil group. 25 A recent meta-analysis of calcineurin inhibitors combined with mTOR versus mycophenolic acid showed increased graft loss, lower renal function, and higher incidence of adverse effects in the sirolimus group. 18 In all the studies reviewed, tacrolimus trough level was high (about 6-10 ng/mL), suggesting that the tacrolimus plus sirolimus combination has different safety profiles that might be related to the trough levels of both drugs, as well as with the immunologic risk of individual kidney recipients.…”

Section: Discussionmentioning

confidence: 99%

Untitled

Kojima

Nga²,

Takase³

et al. 2018

Exp Clin Transplant

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Objectives: There is no consensus on the best immunosuppressive regimen for elderly renal transplant recipients. The objective of this study was to assess cytomegalovirus infection incidence and kidney transplant outcomes in elderly recipients treated with mammalian target of rapamycin inhibitors sirolimus/ tacrolimus at low doses compared with those receiving tacrolimus/mycophenolate sodium. Materials and Methods: In this single-center prospective randomized study (Trial Registration No. NCT02683291), kidney transplant recipients over 60 years of age were randomly allocated into 2 groups: tacrolimus-sirolimus (21 patients) and tacrolimusmycophenolate (23 patients). Cytomegalovirus infec tion rate and patient survival, biopsy-proven acute rejection, and renal function at 12 months were assessed. Results: Cytomegalovirus infection rate was higher in the mycophenolate group (60.9%) than in the sirolimus group (16.7%; P = .004). The rates of biopsy-proven acute rejection, patient survival, graft survival, and estimated glomerular filtration rate over 12 months did not significantly differ between groups. Conclusions: The incidence of cytomegalovirus infection was significantly lower in the sirolimus group. The use of tacrolimus combined with sirolimus in elderly kidney transplant recipients is safe.

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“…Exp Clin Transplant Multicenter, prospective, randomized Low Tac + EVR + S Std Tac + EVR + S (CRADUS09 study, (N=92), 6 mo (Tac C0, 4-7 ng/mL, months 0-3 and TAC (C0, 8-11 ng/mL months 0-3 and Study) 30 3-6 ng/mL, months 4-6); with EVR 7-10 ng/mL months 4-6); EVR (C0, (C0 3 ng/mL); Induction with 3 ng/mL) basiliximab Induction: basiliximab Takahashi et al 28 Prospective, randomized study, SRL (C0, 7-10 ng/mL) + reduced MMF (2 g/d) + reduced TAC (N=82), 8.5 y TAC (C0, 6,-8 ng/mL) (C0, 6-8 ng/mL); Induction: basiliximab and Induction: basiliximab and methylprednisolone methylprednisolone…”

Section: Jayant Kumar Et Al/experimental and Clinical Transplantationmentioning

confidence: 99%

“…Therefore, concentration monitoring has been needed to prevent rejection and toxicity risk. Limited studies have been done so far to assess the transplant outcomes with an mTOR inhibitor-based initial regimen with CNI minimization, with the notable ones being the ASSET study (2012) [22][23][24][25][26][27][28][29] In 2012, Langer and associates in their ASSET study compared de novo introduction of very-lowdose tacrolimus (1.5-3 ng/mL) and everolimus (3-8 ng/mL) with low-dose tacrolimus (1.5-3 ng/mL) and everolimus (3-8 ng/mL). These have been used in a combination with oral steroids following basiliximab induction in renal transplant patients.…”

Section: Mammalian Target Of Rapamycin-based Initial Regimen With Lowmentioning

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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Long-Term Kidney Allograft Function and Survival in Prednisone-Free Regimens

Cited by 45 publications

References 44 publications

Sirolimus and everolimus in kidney transplantation

Sirolimus and everolimus in kidney transplantation

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