Low-Dose Versus High-Dose Cyclosporine Induction Protocols in Renal Transplantation

Ghafari, A.; Makhdoomi, Khadijeh; Pedram, Ahmadpour; Afshari, A. Taghizadeh; Fallah, Mohammadreza Mohammadi; Rad, Pedram

doi:10.1016/j.transproceed.2007.03.014

Cited by 8 publications

(5 citation statements)

References 8 publications

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“…The most widely reported strategy identified by our literature search was CNI minimization, implemented by reducing target trough levels. Thirty‐six RCTs (Table S4) examining dose minimization were identified: 22 studies used CsA, 7 used tacrolimus and 7 incorporated both. Mycophenolic acid formulations (mycophenolate mofetil [MMF] or enteric‐coated mycophenolate sodium [MPS]) were used as adjuvant agents in 19 studies, and 14 used mammalian target of rapamycin (mTOR) inhibitors in addition to CNI.…”

Section: Resultsmentioning

confidence: 99%

Calcineurin Inhibitor Minimization, Conversion, Withdrawal, and Avoidance Strategies in Renal Transplantation: A Systematic Review and Meta‐Analysis

Sawinski

Trofe‐Clark

Leas

et al. 2016

American Journal of Transplantation

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Despite their clinical efficacy, concerns about calcineurin inhibitor (CNI) toxicity make alternative regimens that reduce CNI exposure attractive for renal transplant recipients. In this systematic review and meta-analysis, we assessed four CNI immunosuppression strategies (minimization, conversion, withdrawal, and avoidance) designed to reduce CNI exposure and assessed the impact of each on patient and allograft survival, acute rejection and renal function. We evaluated 92 comparisons from 88 randomized controlled trials and found moderate- to high-strength evidence suggesting that minimization strategies result in better clinical outcomes compared with standard-dose regimens; moderate-strength evidence indicating that conversion to a mammalian target of rapamycin inhibitor or belatacept was associated with improved renal function but increased rejection risk; and moderate- to high-strength evidence suggesting planned CNI withdrawal could result in improved renal function despite an association with increased rejection risk. The evidence base for avoidance studies was insufficient to draw meaningful conclusions. The applicability of the review is limited by the large number of studies examining cyclosporine-based strategies and low-risk populations. Additional research is needed with tacrolimus-based regimens and higher risk populations. Moreover, research is necessary to clarify the effect of induction and adjunctive agents in alternative immunosuppression strategies and should include more comprehensive and consistent reporting of patient-centered outcomes.

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Section: Resultsmentioning

confidence: 99%

Calcineurin Inhibitor Minimization, Conversion, Withdrawal, and Avoidance Strategies in Renal Transplantation: A Systematic Review and Meta‐Analysis

Sawinski

Trofe‐Clark

Leas

et al. 2016

American Journal of Transplantation

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“…The incidence and severity depend on dose [8,9] and duration [15] of treatment, as well as on the patient population studied [10]. The underlying mechanism is complex.…”

Section: Discussionmentioning

confidence: 99%

“…The mechanism is unclear but could be identical to that of cyclosporine. The blood pressure-elevating effects of both calcineurin inhibitors seem to be dose-dependent [8,9].…”

Section: Introductionmentioning

confidence: 96%

Differential effects of acute and sustained cyclosporine and tacrolimus on sympathetic nerve activity

Klein

Abrahams²,

Ede³

et al. 2010

Journal of Hypertension

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Sympathetic overactivity plays a role in the acute hypertensive action of cyclosporine. Cyclosporine given during 2 weeks increases blood pressure and suppresses MSNA, possibly by volume retention. Tacrolimus, in the presently applied dosages, does not cause hypertension or sympathetic overactivity. However, sustained tacrolimus also suppresses sympathetic activity, the reason of which is unclear.

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“…First, the optimal adult rodent dose of 20 mg/kg/d (K m of 6) would scale to 10 mg/kg/d in the 3-to 5-day-old piglet (K m of 12) using allometric scaling (Reagan-Shaw et al, 2008). Second, CsA is administered clinically in doses between 5 and 21 mg/ kg/d (del Mar Fernandez De Gatta et al, 2002;Ghafari et al, 2007;Mazzeo et al, 2009) in humans (K m of 37), which scales to 13-65 mg/kg/d in the 3-to 5-day-old piglet (K m of 12; Reagan-Shaw et al, 2008). It should be noted that children have higher CsA systemic clearance than adults, requiring significantly higher doses and more frequent administration in a transplant cohort (del Mar Fernandez De Gatta et al, 2002).…”

Section: Rapid Non-impact Rotational Injury In Pigletsmentioning

confidence: 99%

Cyclosporin A Preserves Mitochondrial Function after Traumatic Brain Injury in the Immature Rat and Piglet

Kilbaugh

Bhandare

Lorom

et al. 2011

Journal of Neurotrauma

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Cyclosporin A (CsA) has been shown to be neuroprotective in mature animal models of traumatic brain injury (TBI), but its effects on immature animal models of TBI are unknown. In mature animal models, CsA inhibits the opening of the mitochondrial permeability transition pore (MPTP), thereby maintaining mitochondrial homeostasis following injury by inhibiting calcium influx and preserving mitochondrial membrane potential. The aim of the present study was to evaluate CsA's ability to preserve mitochondrial bioenergetic function following TBI (as measured by mitochondrial respiration and cerebral microdialysis), in two immature models (focal and diffuse), and in two different species (rat and piglet). Three groups were studied: injured+CsA, injured+saline vehicle, and uninjured shams. In addition, we evaluated CsA's effects on cerebral hemodynamics as measured by a novel thermal diffusion probe. The results demonstrate that post-injury administration of CsA ameliorates mitochondrial dysfunction, preserves cerebral blood flow (CBF), and limits neuropathology in immature animals 24 h post-TBI. Mitochondria were isolated 24 h after controlled cortical impact (CCI) in rats and rapid non-impact rotational injury (RNR) in piglets, and CsA ameliorated cerebral bioenergetic crisis with preservation of the respiratory control ratio (RCR) to sham levels. Results were more dramatic in RNR piglets than in CCI rats. In piglets, CsA also preserved lactate pyruvate ratios (LPR), as measured by cerebral microdialysis and CBF at sham levels 24 h after injury, in contrast to the significant alterations seen in injured piglets compared to shams (p<0.01). The administration of CsA to piglets following RNR promoted a 42% decrease in injured brain volume (p<0.01). We conclude that CsA exhibits significant neuroprotective activity in immature models of focal and diffuse TBI, and has exciting translational potential as a therapeutic agent for neuroprotection in children.

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Low-Dose Versus High-Dose Cyclosporine Induction Protocols in Renal Transplantation

Cited by 8 publications

References 8 publications

Calcineurin Inhibitor Minimization, Conversion, Withdrawal, and Avoidance Strategies in Renal Transplantation: A Systematic Review and Meta‐Analysis

Calcineurin Inhibitor Minimization, Conversion, Withdrawal, and Avoidance Strategies in Renal Transplantation: A Systematic Review and Meta‐Analysis

Differential effects of acute and sustained cyclosporine and tacrolimus on sympathetic nerve activity

Cyclosporin A Preserves Mitochondrial Function after Traumatic Brain Injury in the Immature Rat and Piglet

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