Association of Cumulative Cyclosporine Dose with Its Irreversible Nephrotoxicity in Japanese Patients with Pediatric-Onset Autoimmune Diseases

Tsutomu Nakamura; Kandai Nozu; Kazumoto Iijima; Norishige Yoshikawa; Yuka Moriya; Motohiro Yamamori; Asae Kako; Masafumi Matsuo; Aki Sakurai; Noboru Okamura; Toshihisa Ishikawa; Katsuhiko Okumura; Toshiyuki Sakaeda

doi:10.1248/bpb.30.2371

Regular Articles

Association of Cumulative Cyclosporine Dose with Its Irreversible Nephrotoxicity in Japanese Patients with Pediatric-Onset Autoimmune Diseases

Tsutomu Nakamura, Kandai Nozu, Kazumoto Iijima, Norishige Yoshikawa, Yuka Moriya, Motohiro Yamamori, Asae Kako, Masafumi Matsuo, Aki Sakurai, Noboru Okamura, Toshihisa Ishikawa, Katsuhiko Okumura, Toshiyuki Sakaeda

Author information

Tsutomu Nakamura
Department of Hospital Pharmacy, Kobe University School of Medicine
Kandai Nozu
Department of Pediatrics, Kobe University Graduate School of Medicine
Kazumoto Iijima
Department of Nephrology, National Center for Child Health and Development
Norishige Yoshikawa
Department of Pediatrics, Wakayama Medical University
Yuka Moriya
Department of Hospital Pharmacy, Kobe University School of Medicine
Motohiro Yamamori
Department of Hospital Pharmacy, Kobe University School of Medicine
Asae Kako
Department of Hospital Pharmacy, Kobe University School of Medicine
Masafumi Matsuo
Department of Pediatrics, Kobe University Graduate School of Medicine
Aki Sakurai
Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology
Noboru Okamura
Department of Clinical Evaluation of Pharmacotherapy, Kobe University Graduate School of Medicine
Toshihisa Ishikawa
Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology
Katsuhiko Okumura
Department of Hospital Pharmacy, Kobe University School of Medicine
Department of Clinical Evaluation of Pharmacotherapy, Kobe University Graduate School of Medicine
Toshiyuki Sakaeda
Department of Hospital Pharmacy, Kobe University School of Medicine
Center for Integrative Education of Pharmacy Frontier, Graduate School of Pharmaceutical Sciences, Kyoto University

Keywords: cyclosporine, auto-immune disease, nephrotoxicity, pediatric patient

JOURNAL FREE ACCESS

2007 Volume 30 Issue 12 Pages 2371-2375

DOI https://doi.org/10.1248/bpb.30.2371

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Abstract

Cyclosporine (CsA)-induced nephrotoxicity can become a major obstacle to continuous use. The aim of this study was to optimize CsA dose to avoid its irreversible nephrotoxicity. Twenty-three Japanese patients with pediatric-onset systemic lupus erythematosus or idiopathic nephrotic syndrome, who were maintained in a stable condition by oral dosing of CsA microemulsion, were enrolled in this study. The patients were stratified into 3 groups; those with no, reversible, and irreversible nephrotoxicity, according to periodically performed renal pathohistological examinations. A higher concentration of CsA in blood (p=0.002—0.011) and a longer duration of CsA treatment (p=0.002) were risk factors for irreversible nephrotoxicity, and the cumulative CsA dose, the product of the maintenance dose and duration of CsA treatment, was predictive of nephrotoxicity (p=0.036). The maximum target blood concentration at 2 h post-dose, C₂, to avoid CsA-induced irreversible nephrotoxicity was 700 ng/ml, although the cumulative CsA dose of 4850 mg/kg would result in a 50% probability of nephrotoxicity.

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