Reduced Exposure to Calcineurin Inhibitors in Renal Transplantation

Ekberg, Henrik; Tedesco‐Silva, Hélio; Demirbaş, A.; Vı́tko, Štefan; Nashan, Björn; Gürkan, Alp; Margreiter, Raimund; Hugo, Christian; Grinyó, Josep M.; Frei, Ulrich; Vanrenterghem, Yves; Daloze, Pierre; Halloran, Philip F.

doi:10.1056/nejmoa067411

Cited by 1,660 publications

(1,406 citation statements)

References 20 publications

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“…However, clinically no consistent long-term benefit for graft outcomes was noted in sirolimus-based calcineurin inhibitor-sparing protocols (242). Indeed the lower pro-fibrogenic activity of sirolimus may be offset by higher rejections rates, as illustrated by the ELITE-SYMPHONY trial (243). Another randomized controlled trial also failed to demonstrate less allograft fibrosis at one year after switching to a sirolimus-based regimen as compared to a cyclosporine regimen despite better GFR in the former (244).…”

Section: Key Molecular Effector Systems and Therapies In Renal Fibrosismentioning

confidence: 99%

Renal Allograft Fibrosis: Biology and Therapeutic Targets

Floege

2015

American Journal of Transplantation

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Section: Key Molecular Effector Systems and Therapies In Renal Fibrosismentioning

confidence: 99%

Renal Allograft Fibrosis: Biology and Therapeutic Targets

Floege

2015

American Journal of Transplantation

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“…The incidence of DGF was high probably due to the characteristics of the transplantations performed, and was not influenced by the induction therapy used. 25 The overall incidence of BPAR (18.5%) was relatively greater when compared with the incidence of rejection observed in patients with no DGF, usually ranging from 10% to 12%. 26 Patients undergoing alemtuzumab induction showed a higher incidence of acute rejection (33.3% vs. 11.1%) and graft loss (33.3% vs. 22.2%) as compared with those receiving thymoglobulin, probably due to shorter duration of its pharmacodynamic effect, here analyzed through the reduction in lymphocyte count in peripheral blood.…”

Section: Discussionmentioning

confidence: 86%

Terapia de indução com alentuzumabe em receptores de transplante renal

Sampaio¹,

Freitas²,

Galante³

et al. 2010

J. Bras. Nefrol.

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Introduction: Induction therapy has been used in sensitized patients, re-transplants, and in patients who have high risk to delayed graft function (DGF) after renal transplantation. Methods: Retrospective study with aim to compare transplant endpoints between recipients of deceased donors which have received induction with alemtuzumab (n = 9) versus thymoglobulin (n = 18). Patients were matched for age, duration of dialysis treatment and cold ischemia time. Results: There were no differences at demographic characteristics. All patients received kidney grafts from deceased donors and 67% of these donors met the expanded criteria. The incidence of DFG was similar in alemtuzumab and thymoglobulin groups, 55% and 56%. At 12 months, rates of rejection free survival (67% versus 89%, p = 0,13), graft survival (62,5% versus 76,6%; p = 0,73), graft with death censored (62,5% versus 76,6%; p = 0,82) and patient survival (83,3% versus 81,2%; p = 0,63) were similar between the two groups. Viral infections and renal function were similar between groups. At the end of the first month, alemtuzumab patients displayed a fewer lymphocyte number (135 ± 78 versus 263 ± 112 N/mm 3 , p < 0,05) followed by a more rapid recovery after 3 months (day 90: 683 ± 367 versus 282 ± 72 N/mm 3 ; p < 0,05). Cost associated with alemtuzumab and thymoglobulin inductions therapies were R$ 1,388.00 and R$ 7,398.00. Conclusion: In this cohort of patients, alemtuzumab induction showed efficacy and safety comparable to thymoglobulin but with significant cost reduction.

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“…It is possible that cyclosporine is more nephrotoxic than tacrolimus or that, historically, cyclosporine was used at higher equivalent concentrations than tacrolimus is used in current practice. In the Elite‐SYMPHONY study, low‐dose tacrolimus (target trough concentration 3‐7 ng/mL, similar to that used in the 3C Study) provided better transplant function at 1 year compared with standard‐ or low‐dose cyclosporine 5. Consistent with this is a recent report from the Westmead Hospital, Sydney, which found less evidence of nephrotoxicity in serial protocol kidney biopsy samples taken from kidney–pancreas transplant recipients between 1999 and 2012 (an era when tacrolimus was the predominant CNI) compared with those taken between 1987 and 2000 (when cyclosporine was used) 3.…”

Section: Discussionmentioning

confidence: 99%

Campath, calcineurin inhibitor reduction, and chronic allograft nephropathy (the 3C Study) – results of a randomized controlled clinical trial

Haynes

Blackwell

Staplin

et al. 2018

American Journal of Transplantation

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Calcineurin inhibitors (CNIs, eg, tacrolimus) reduce short‐term kidney transplant failure, but chronic nephrotoxicity may contribute to late transplant loss. Elective conversion to inhibitors of the mammalian target of rapamycin (mTOR, eg, sirolimus) pathway might avoid long‐term CNI renal damage and improve outcomes. The 3C Study was a pragmatic randomized controlled trial of sequential randomizations between alemtuzumab and basiliximab induction therapy (at the time of surgery) and between tacrolimus and sirolimus maintenance therapy at 6 months posttransplantation. The primary outcome of this analysis was estimated glomerular filtration rate (eGFR) at 18 months after maintenance therapy randomization; 197 patients were assigned sirolimus‐based and 197 to tacrolimus‐based therapy. Allocation to sirolimus had no significant effect on eGFR at 18 months: baseline‐adjusted mean (SEM) eGFR was 53.7 (0.9) mL/min/1.73 m2 in the sirolimus group versus 54.6 (0.9) mL/min/1.73 m2 in the tacrolimus group (P = .50). Biopsy‐proven acute rejection (29 [14.7%]) vs 6 [3.0%]; P < .001) and serious infections (defined as opportunistic infections or those requiring hospitalization; 95 [48.2%] vs 70 [35.5%]; P = .008) were more common among participants allocated sirolimus. Compared with tacrolimus‐based therapy, sirolimus‐based maintenance therapy did not improve transplant function at 18 months after conversion and was associated with significant hazards of rejection and infection. ClinicalTrials.gov identifier NCT01120028 and ISRCTN88894088.

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Reduced Exposure to Calcineurin Inhibitors in Renal Transplantation

Cited by 1,660 publications

References 20 publications

Renal Allograft Fibrosis: Biology and Therapeutic Targets

Renal Allograft Fibrosis: Biology and Therapeutic Targets

Terapia de indução com alentuzumabe em receptores de transplante renal

Campath, calcineurin inhibitor reduction, and chronic allograft nephropathy (the 3C Study) – results of a randomized controlled clinical trial

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