Calcineurin Activity Assay Measurement by Liquid Chromatography–Tandem Mass Spectrometry in the Multiple Reaction Monitoring Mode

Carr, Lynn; Gagez, Anne-Laure; Essig, Marie; Sauvage, François‐Ludovic; Marquet, Pierre; Gastinel, Louis N.

doi:10.1373/clinchem.2013.213264

Cited by 17 publications

(6 citation statements)

References 22 publications

(22 reference statements)

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“…Serum CaN activity was assayed in the presence or absence of 10 m M EGTA, a CaN inhibitor, essentially according to the method of Carr et al [12] with minor modifications. Assays were conducted in a final volume of 50 μL containing 5 μL of sample solution and 45 μL of substrate solution.…”

Section: Methodsmentioning

confidence: 99%

Correlation between Serum Calcineurin Activity and Left Ventricular Hypertrophy in Hypertensive Patients and Its Clinical Significance

Cao

Yang²,

Nabeel³

et al. 2018

Cardiology

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Objective: The aim of this study is to investigate the correlation between calcineurin (CaN) and hypertension with left ventricular hypertrophy (HLVH) and to evaluate its potential clinical significance. Design: The study involved 160 patients diagnosed with hypertension and 42 controls. Based on the exclusion criteria, 42 were not eligible for this study. The remaining 118 hypertensive patients were categorized into 2 subgroups based on left ventricular mass index and relative ventricular wall thickness: a normal model subgroup with hypertension (HNM) and an HLVH subgroup. Serum CaN levels were determined by enzyme-linked immunosorbent assay, while serum CaN activity was determined by malachite green colorimetric assay. Results: Among the HNM and HLVH subgroups, a positive correlation was demonstrated between serum CaN activity, but not serum CaN level, and HLVH. Moreover, the HLVH subgroup displayed a remarkable increase in the levels of brain natriuretic peptide, cystatin C, urinary albumin/creatinine ratio, and left atrium diameter compared to the HNM subgroup and controls. Conclusion: There was a positive correlation between serum CaN activity and LVH in hypertensive patients. Activated CaN could play an important role in the pathophysiologic mechanism of HLVH. Serum CaN activity could be a clinically useful diagnostic and prognostic biomarker for LVH.

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Section: Methodsmentioning

confidence: 99%

Correlation between Serum Calcineurin Activity and Left Ventricular Hypertrophy in Hypertensive Patients and Its Clinical Significance

Cao

Yang²,

Nabeel³

et al. 2018

Cardiology

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“…The CVs of LC-MS/MS for therapeutic drug monitoring of tacrolimus for the patient samples ranged from 2.0% to 5.4% (ANNESLEY & al [17]) and LC-MRM-MS was commonly used in routine clinical dosage of tacrolimus (CARR & al [18]). All methods that used MS/MS or LC-MS/MS proved more difficult from a practical point of view, requiring specialized staff and thus yielding results lower, albeit with a much better specificity.…”

Section: The Analysis Of Tacrolimus Concentrations Agreement Between mentioning

confidence: 99%

Tacrolimus concentrations by ELISA and LC - MS/MS

ALDEA¹,

DELEAN²,

BULATA³

et al. 2019

Rom Biotechnol Lett.

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Introduction. Tacrolimus has immunosuppressive effects in vitro through the inhibition of mixed lymphocyte reactivity and the generation of cytotoxic T cells. There is a wide variety of laboratory methods for monitoring of immunosuppressive drugs. There is a growing clinical needfor a new evaluation of these methods. Material and Method. A total of 17 transplant patients were retrospectively analyzed. This study aimed to evaluate the concordance between ELISA and LC-MS/MS methods for measurement of tacrolimus serum trough levels. Result. Mean tacrolimus blood concentrations in these patients ranged from 2.43-10.07 ng/ml for the ELISA and 3.1-7.6 ng/ml for the LC-MS/MS. We found a concordance between ELISA and LC-MS/MS but the inter-subject variance coefficient for the ELISA method was higher than inter-subject variance coefficient for LC-MS/MS. Conclusion. The results point out the advantages of LC-MS/MS over ELISA in monitoring tacrolimus levels in pediatric kidney transplanted patients. The lower inter-subject variance of LC-MS/MS could result in fewer dose changes and an overall better immunosuppression control.

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“…Unfortunately, no isoform-specific calcineurin substrate has been discovered [67]. Using Liquid Chromatography-Multiple Reaction Monitoring Mass Spectrometry (LC-MRMMS) Carr et al [68] quantified CN activity by measuring the dephosphorylation of a synthetic phosphopeptide substrate. The assay was used to determine CN activity in Peripheral Blood Mononuclear Cells (PBMCs) isolated from 20 CNI-treated kidney transplant patients and nine healthy volunteers.…”

Section: Gr Up Smmentioning

confidence: 99%

Calcineurin Inhibitor - A Necessary Evil: Pharmacogenetical Approach to a Promising Future

Zhang¹,

Gu²,

Huang³

et al. 2015

SM J Uro

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The backbone of modern immunosuppressant regimens after kidney transplantation is Calcineurin Channel Inhibitor (CNI) drugs including tacrolimus and cyclosporine A. Its mechanism is binding to immunophilins, forming complexes, binding to calcineurin, and leading to inhibition of T cell activation. Since CNI drugs are eliminated by cytochrome P450 system, especially the CYP3A subfamily, exploring their interaction exhibits great importance. It is known that CYP3A4 and CYP3A5 are involved in tacrolimus metabolism while CYP3A5 alone plays a major role in cyclosporine A metabolism. The polymorphism of CYP3A4 and CYP3A5 genes results in different CNI drugs dose requirements in transplant recipients. Pharmacogenetic approaches to figure out donors' and recipients' CYP3A4 and CYP3A5 genotypes may give us better understanding of pharmacodynamics of CNI drugs. Additionally, monitoring CNI blood concentration can reflect its pharmacokinetics. Combination of pharmacodynamics and pharmacokinetics may be used as a guide in clinical practice to administer CNI drugs in optimal dose, to avoid acute rejection or adverse effects of CNI drugs such as nephrotoxicity.

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Calcineurin Activity Assay Measurement by Liquid Chromatography–Tandem Mass Spectrometry in the Multiple Reaction Monitoring Mode

Cited by 17 publications

References 22 publications

Correlation between Serum Calcineurin Activity and Left Ventricular Hypertrophy in Hypertensive Patients and Its Clinical Significance

Correlation between Serum Calcineurin Activity and Left Ventricular Hypertrophy in Hypertensive Patients and Its Clinical Significance

Tacrolimus concentrations by ELISA and LC - MS/MS

Calcineurin Inhibitor - A Necessary Evil: Pharmacogenetical Approach to a Promising Future

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