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Cyclosporine A C1.5 monitoring reflects the area under the curve in children with nephrotic syndrome: a single-center experience

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Abstract

Background

The currently used single-monitoring method for drug–blood-level evaluation in cyclosporine A (CsA) treatment for nephrotic syndrome (NS) was established through hourly measurements based on adult organ transplantation. However, the pharmacokinetics may differ due to different concomitant medications, age, and conditions. This study was conducted to determine the measurement timing that best reflects the CsA area under the curve (AUC) in pediatric NS.

Methods

This retrospective study included children aged 2–14 years who were started on CsA treatment for idiopathic NS during 2013–2020. AUC0–4 was calculated from 7 points, before and 0.5, 1, 1.5, 2, 3, and 4 h after administration. Mean values at each timing were compared with age-dependent different drug forms. Correlation between AUC0–4 and measurement timing was analyzed.

Results

There were 13 patients (11 boys) whose median age during testing was 7.3 years, and the total number of measurements was 94. The highest timing of CsA concentrations was found in C1 59.6%. The content liquid used at younger ages had a faster absorption time to peak value and lower blood concentration than those of capsules. Among the significant correlations observed, AUC0–4 and C1.5 showed the strongest significant correlation coefficient (r = 0.93, P < 0.001).

Conclusion

In pediatric NS, CsA metabolism may be faster than that in previous organ transplantation. Compared with C2, C1.5 monitoring may result in better disease control as it can best reflect the AUC0–4 and peak values associated with side effects, which are indicators of therapeutic efficacy.

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Availability of data and materials

The datasets generated during and/or analyzed in the present study are available from the corresponding author on reasonable request.

Code availability

Not applicable.

Abbreviations

AUC:

Area under the curve

CsA:

Cyclosporine A

ECLIA:

Electro-chemiluminescence immunoassay

EMIT:

Enzyme-multiplied immunoassay technique

NS:

Nephrotic syndrome

SRNS:

Steroid-resistant nephrotic syndrome

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Funding

This study received no specific grants from any funding agency in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Pediatrics, Teikyo University School of Medicine, 2-11-1, Kaga, Itabashi-ku, Tokyo, 173-8605, Japan

    Tomohiko Nishino, Kazuhiro Takahashi, Shinya Tomori, Sayaka Ono & Masakazu Mimaki

Authors
  1. Tomohiko Nishino
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  2. Kazuhiro Takahashi
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  3. Shinya Tomori
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  4. Sayaka Ono
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  5. Masakazu Mimaki
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Contributions

All authors contributed to the study conception and design. The authors TN and KT contributed equally to this work. TN mainly drafted the manuscript, data collection and performed the statistical analysis; TN, KT and ST contributed to the material preparation and data collection; KT and SO critically reviewed the manuscript; MM supervised the whole study process. All authors read and approved the final manuscript.

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Correspondence to Tomohiko Nishino.

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Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

The study was approved by the Teikyo University Ethical Review Board for Medical and Health Research Involving Human Subjects (approval number 20-195-2). All procedures in studies involving human participants were performed in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Consent to participate/Consent for publication

The study plan outline was presented on the Teikyo University website, where patients and their guardians could ask questions about the study and opt out from the use of their data. Informed consent to participate and publication was obtained on the before blood sampling. The study was explained to all patients and their parents/guardians in plain language with explanatory documents, and written consent for participation in research and publication was obtained from the parents/guardians of all subjects. At the same time, it was clarified that the parents/guardians had the right to refuse participation and withdraw consent at will.

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Nishino, T., Takahashi, K., Tomori, S. et al. Cyclosporine A C1.5 monitoring reflects the area under the curve in children with nephrotic syndrome: a single-center experience. Clin Exp Nephrol 26, 154–161 (2022). https://doi.org/10.1007/s10157-021-02139-z

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