A 50% reduction in cyclosporine exposure in stable renal transplant recipients: renal function benefits

Étienne, Isabelle; Toupance, Olivier; Bénichou, Jacques; Thierry, Antoine; Najjar, Azmi Al; Ligny, Bruno Hurault de; Meur, Yann Le; Westeel, Pierre-François; Marquet, Pierre; Audigier, François; Hellot, Marie‐France; Godin, Michel

doi:10.1093/ndt/gfq135

Cited by 23 publications

(21 citation statements)

References 31 publications

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“…(20) Other studies suggest that approaching the immunosuppressive regimen in stable RTRs with a minimalisation strategy may reduce the risk of graft dysfunction and complication such as cardiovascular disease or malignancy. (21)(22)(23)(24) However, there is little recommendation or consensus on immunosuppressant dose reduction in RTRs under severe infectious conditions. Reduction of immunosuppressants in RTRs according to the KDIGO guidelines may be indicated in opportunistic infections such as those due to Epstein-Barr virus, herpes simplex virus types 1 and 2, varicella-zoster virus, Herpes zoster virus, lifethreatening CMV disease, polyomavirus and P. jirovecii.…”

Section: Discussionmentioning

confidence: 99%

Immunosuppressant dose reduction and long-term rejection risk in renal transplant recipients with severe bacterial pneumonia

Shih¹,

Tarng²,

Wu³

et al. 2014

smedj

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Section: Discussionmentioning

confidence: 99%

Immunosuppressant dose reduction and long-term rejection risk in renal transplant recipients with severe bacterial pneumonia

Shih¹,

Tarng²,

Wu³

et al. 2014

smedj

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“…Short-term studies have proven the positive impact of CsA dose reduction with concomitant MMF administration on renal graft function [11]. In a recent publication concerning the DICAM study, a prospective randomized trial confirms these results [12]. However, the study of long-term consequences of this approach is important, given the possibility that the observed short-term improvements might be the outcome of the elimination of the functional CNI nephrotoxicity of vascular origin, and that lesions in relation to reduced immunosuppression could eventually result in graft loss.…”

Section: Introductionmentioning

confidence: 97%

Long-Term Impact of Cyclosporin Reduction with MMF Treatment in Chronic Allograft Dysfunction: REFERENECE Study 3-Year Follow Up

Frimat

Cassuto‐Viguier

François

et al. 2010

Journal of Transplantation

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Calcineurin inhibitor (CNI) toxicity contributes to chronic allograft nephropathy (CAN). In the 2-year, randomized, study, we showed that 50% cyclosporin (CsA) reduction in combination with mycophenolate mofetil (MMF) treatment improves kidney function without increasing the risk for graft rejection/loss. To investigate the long-term effect of this regimen, we conducted a follow up study in 70 kidney transplant patients until 5 years after REFERENCE initiation. The improvement of kidney function was confirmed in the MMF group but not in the control group (CsA group). Four graft losses occurred, 2 in each group (graft survival in the MMF group 95.8% and 90.9% in control group). One death occurred in the control group. There was no statistically significant difference in the occurrence of serious adverse events or acute graft rejections. A limitation is the weak proportion of patient still remaining within the control group. On the other hand, REFERENCE focuses on the CsA regimen while opinions about the tacrolimus ones are still debated. In conclusion, CsA reduction in the presence of MMF treatment seems to maintain kidney function and is well tolerated in the long term.

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“…The low occurrence of BPAR (4.9%) in the follow‐up study is in accordance with the study published by Etienne et al . in which a minimization based on CsA low‐dose exposure is associated with an incidence of BPAR of 6% at 24 months . However, in our study, six grafts were lost over 10‐year follow‐up because of chronic ABMR.…”

Section: Discussionmentioning

confidence: 54%

Minimization of maintenance immunosuppressive therapy after renal transplantation comparing cyclosporine A/azathioprine or cyclosporine A/mycophenolate mofetil bitherapy to cyclosporine A monotherapy: a 10-year postrandomization follow-up study

et al. 2016

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Long-term outcomes in renal transplant recipients withdrawn from steroid and submitted to further minimization of immunosuppressive regimen after 1 year are lacking. In this multicenter study, 204 low immunological risk kidney transplant recipients were randomized 14.2 ± 3.7 months post-transplantation to receive either cyclosporine A (CsA) + azathioprine (AZA; n = 53), CsA + mycophenolate mofetil (MMF; n = 53), or CsA monotherapy (n = 98). At 3 years postrandomization, the occurrence of biopsy for graft dysfunction was similar in bitherapy and monotherapy groups (21/106 vs. 26/98; P = 0.25). At 10 years postrandomization, patients' survival was 100%, 94.2%, and 95.8% (P = 0.25), and death-censored graft survival was 94.9%, 94.7%, and 95.2% (P = 0.34) in AZA, MMF, and CsA groups, respectively. Mean estimated glomerular filtration rate was 70.4 ± 31.1, 60.1 ± 22.2, and 60.1 ± 19.0 ml/min/1.73 m(2), respectively (P = 0.16). The incidence of biopsy-proven acute rejection was 1.4%/year in the whole cohort. None of the patients developed polyomavirus-associated nephropathy. The main cause of graft loss (n = 12) was chronic antibody-mediated rejection (n = 6). De novo donor-specific antibodies were detected in 13% of AZA-, 21% of MMF-, and 14% of CsA-treated patients (P = 0.29). CsA monotherapy after 1 year is safe and associated with prolonged graft survival in well-selected renal transplant recipient (ClinicalTrials.gov number: 980654).

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A 50% reduction in cyclosporine exposure in stable renal transplant recipients: renal function benefits

Abstract: In renal transplant recipients receiving maintenance therapy without corticosteroids, a minimization strategy using three-point pharmacokinetic sampling to reduce and maintain cyclosporine exposure to 50% of the usual levels is safe and reduces the risk of graft dysfunction.

Cited by 23 publications

References 31 publications

Immunosuppressant dose reduction and long-term rejection risk in renal transplant recipients with severe bacterial pneumonia

Immunosuppressant dose reduction and long-term rejection risk in renal transplant recipients with severe bacterial pneumonia

Long-Term Impact of Cyclosporin Reduction with MMF Treatment in Chronic Allograft Dysfunction: REFERENECE Study 3-Year Follow Up

Minimization of maintenance immunosuppressive therapy after renal transplantation comparing cyclosporine A/azathioprine or cyclosporine A/mycophenolate mofetil bitherapy to cyclosporine A monotherapy: a 10-year postrandomization follow-up study

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