Benefit of Neoral C2 Monitoring in De Novo Cardiac Transplant Recipients Receiving Basiliximab Induction

Cantarovich, Marcelo; Ross, Heather J.; Arizón, José M.; Gómez, Miguel Ángel; Straatman, Lynn; Orús, Josefina; Alonso‐Pulpón, Luis; Molina, Beatriz Díaz; Wang, Shaohua; Lage, E.; Crespo, M.; Manito, Nicolás; Howlett, Jonathan G.; Haddad, Haissam

doi:10.1097/tp.0b013e318169bf43

Cited by 17 publications

(14 citation statements)

References 26 publications

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“…Calcineurin inhibitors may interfere with ATG-induced apoptosis of activated lymphocytes, resulting in decreased efficacy; 36 consistent with this, heart transplant patients receiving an anti-CD25 (IL-2 receptor) Ab exposed to lower C2 levels had a lower rate of graft rejection. 9 Moreover, measurement of C2 levels or AUC may not be the optimal way of assessing the biological effect of CsA. Significant inter-patient variability in the degree of calcineurin inhibition produced by a consistent dose of CsA 37 has 'emphasised the importance of correlating biological measures of calcineurin inhibition with clinical outcome'.…”

Section: Discussionmentioning

confidence: 99%

“…[5][6][7] In solid organ transplantation, the use of C0 monitoring has been associated with a high incidence of renal dysfunction. 8 In these patients, levels taken 2 h after a dose (C2) appear to correlate best with C max and area under the concentration-time curve 0-4 h (AUC 0À4h ), 9 and monitoring and dose adjustments based on C2 levels has been associated generally with improved renal function without an increased risk of graft rejection after heart, 10 liver 11 and renal transplantation, 12 although not all studies have demonstrated benefit with this approach. 13,14 Alterations in GI motility and mucosal integrity by conditioning regimens or GVHD mean that observations in solid organ transplantation may not apply to recipients of allo-SCT.…”

Section: Introductionmentioning

confidence: 99%

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CsA 2-h concentration correlates best with area under the concentration–time curve after allo-SCT compared with trough CsA

Kong

Shuttleworth

Bailey

et al. 2011

Bone Marrow Transplant

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The relationship between CsA levels and area under the curve (AUC) in allo-SCT recipients, and the effect of age, concomitant use of steroid and MDR-1 polymorphism on this relationship remain largely unexplored. Steady-state CsA blood concentrations at time 0 (C0), 1 (C1), 1.5 (C1.5), 2 (C2), 3 (C3), 4 (C4), 6 (C6), 8 (C8) and 12 (C12) h post oral CsA dose were taken from 27 consenting allo-SCT recipients (receiving myeloablative or nonmyeloablative conditioning) at D 15 -D 25 (all participants) and D 40 -D 80 (participants with myeloablative conditioning). The CsA AUC 0À4h , AUC 0À8h and AUC 0À12h were determined using trapezoidal rule, and the relationships between AUCs and CsA concentrations at various time points were examined. Poor correlation was observed between C0 and AUC 0À4h (r 2 ¼ 0.15), AUC 0À8h (r 2 ¼ 0.21) and AUC 0À12h (r 2 ¼ 0.53). C2 was better correlated with AUC 0À4h (r 2 ¼ 0.88), AUC 0À8h (r 2 ¼ 0.76) and AUC 0À12h (r 2 ¼ 0.83). The aforementioned factors did not influence the observed relationship. CsA levels taken at 2 h post oral CsA administration may represent the optimal time point for monitoring the biological effects of calcineurin inhibitors in allo-SCT recipients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CsA 2-h concentration correlates best with area under the concentration–time curve after allo-SCT compared with trough CsA

Kong

Shuttleworth

Bailey

et al. 2011

Bone Marrow Transplant

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“…As cohort B patients were randomized into two reduced doses without a standard dose, we considered only cohort A. Patients randomized into ‘high’ C 2 range were the ‘standard‐CNI’ group, and those randomized into the ‘intermediate’ and ‘low’ C 2 range were included in the ‘low‐CNI’ group .…”

Section: Resultsmentioning

confidence: 99%

“…No kidney protection by CNI reduction was observed in several studies , whereas other studies found either a trend or better kidney protection, with the greatest benefit immediately after transplantation . In the study by Cantarovich et al ., the lower C 2 group was associated with a trend towards a lower incidence of acute rejection . Potena et al .…”

Section: Discussionmentioning

confidence: 99%

Impact of the reduction of calcineurin inhibitors on renal function in heart transplant patients: a systematic review and meta‐analysis

Cornu

Dufays

Gaillard

et al. 2014

Brit J Clinical Pharma

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AIMSCalcineurin inhibitors (CNIs) taken after heart transplantation lead to excellent short-term outcomes, but long-term use may cause chronic nephrotoxicity. Our aim was to identify, appraise, select and analyse all high-quality research evidence relevant to the question of the clinical impact of CNI-sparing strategies in heart transplant patients. METHODSWe carried out a systematic review and meta-analysis of randomized controlled trials on CNI reduction in heart transplant recipients. Primary outcomes were kidney function and acute rejection after 1 year. Secondary outcomes included graft loss, all-cause mortality and adverse events. RESULTSEight open-label studies were included, with 723 patients (four tested de novo CNI reduction and four maintenance CNI reduction). Calcineurin inhibitor reduction did not improve creatinine clearance at 12 months 5.46 [−1.17, 12.03] P = 0.32 I 2 = 65.4%. Acute rejection at 12 months (55/360 vs. 52/332), mortality (18/301 vs. 15/270) and adverse event rates (55/294 vs. 52/281) did not differ between the low-CNI and standard-CNI groups. There was significant benefit on creatinine clearance in patients with impaired renal function at 6 months [+12.23 (+5.26, +18.82) ml min −1 , P = 0.0003] and at 12 months 4.63 [−4.55, 13.82] P = 0.32 I 2 = 75%. CONCLUSIONSThis meta-analysis did not demonstrate a favourable effect of CNI reduction on kidney function, but there was no increase in acute rejection. To provide a better analysis of the influence of CNI reduction patterns and associated treatments, a meta-analysis of individual patient data should be performed.

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“…This scheme has been optimized and evolved to monitor a single sample at 2 H with the introduction of CsA microemulsion (Neoral R ) [8]. C2 monitoring has been shown to be predictive of outcomes in solid-organ transplants and compared with the conventionally measured trough level (C0), and has been shown to reflect the AUC and adequately estimate oral adsorption in transplant patients [9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

The Emit® 2000 Cyclosporine Specific Assay, Extended Range: Development of an application protocol for the V‐Twin® Analyzer

Morjana

Yau

Rea

et al. 2011

Biotech and App Biochem

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We evaluated a new protocol for measurement of cyclosporine A (CsA) 2 H after dose (C2) on the V-Twin® analyzer. Imprecision, recovery, and linearity were determined using CsA-spiked blood pools. Accuracy was evaluated using specimens from renal, cardiac, and liver transplant patients, and results were compared with those from liquid chromatography-tandem mass spectrometry (LC-MS/MS) and the Abbott TDx®/TDxFLx® assay. Cross-reactivity and interferences were assessed in the presence of 800 ng/mL CsA. Imprecision coefficients of variation were 3.3%-4.8% (within run) and 5.9%-8.7% (total). Recovery was within 10% of the expected values. Linearity was 350-2,000 ng/mL. Calibration was stable for ≥ 2 weeks. Method comparison showed regression statistics: V-Twin® = 1.01 × LC tandem MS + 36.1, r = 0.971; V-Twin® = 1.13 × Abbott - 92.4, r = 0.969. Metabolite cross-reactivity and interference (endogenous substances and drugs) were within ±10%. The C2 protocol on the V-Twin® analyzer provides acceptable assay performance and accurate determination of whole blood CsA drawn at 2 H after dose.

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Benefit of Neoral C2 Monitoring in De Novo Cardiac Transplant Recipients Receiving Basiliximab Induction

Abstract: These results suggest that C2 monitoring is safe in de novo heart transplant patients. A low Neoral C2 range in combination with basiliximab induction resulted in preserved renal function without increased risk of acute rejection.

Cited by 17 publications

References 26 publications

CsA 2-h concentration correlates best with area under the concentration–time curve after allo-SCT compared with trough CsA

CsA 2-h concentration correlates best with area under the concentration–time curve after allo-SCT compared with trough CsA

Impact of the reduction of calcineurin inhibitors on renal function in heart transplant patients: a systematic review and meta‐analysis

The Emit® 2000 Cyclosporine Specific Assay, Extended Range: Development of an application protocol for the V‐Twin® Analyzer

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