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Nephrotoxicity in children with frequently relapsing nephrotic syndrome receiving long-term cyclosporine treatment

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Abstract

Background

Steroid-sparing drugs, such as cyclosporine, are recommended as treatment for children with frequently relapsing nephrotic syndrome (FRNS) and steroid-related toxicities. We recently reported a high rate of relapsing nephrotic syndrome 2 years after discontinuation of cyclosporine treatment, suggesting that long-term treatment is necessary. Cyclosporine-associated nephrotoxicity (CAN) is a potential side effect of long-term cyclosporine treatment.

Methods

We retrospectively reviewed pediatric patients with FRNS treated with cyclosporine for ≥3 years at a single center between 1999 and 2012. The cyclosporine dose was adjusted to maintain the whole-blood cyclosporine trough level at 80–100 ng/ml for 6 months, at 60–80 ng/ml for 18 months, and then at around 50–60 ng/ml thereafter. Maintenance dose of prednisolone was not prescribed. CAN was graded in terms of arteriolar hyalinosis and the degree of interstitial fibrosis.

Results

Thirty-six children (28 males) were enrolled in the study. The median age at the start of long-term cyclosporine treatment was 9.4 years. The median duration of the longest period of cyclosporine treatment was 4.5 years. Most CAN cases were characterized by arteriolar hyalinosis. The frequency of CAN was positively correlated with the duration of cyclosporine treatment, with an odds ratio (95% confidence interval) for CAN of 3.84 (0.79–18.74) after 2–5 years and 6.60 (1.18–36.94) after >5 years of cyclosporine treatment (vs. 0–2 years).

Conclusions

Although the frequency of CAN was correlated with the duration of cyclosporine treatment in our pediatric patient population, most cases of CAN involved arteriolar hyalinosis. We conclude that long-term cyclosporine treatment is useful for treating FRNS in children, providing its dose is controlled and kidney biopsies are regularly performed.

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Acknowledgments

The authors wish to thank Nicholas Smith, PhD, of Edanz Group Japan K.K., for providing editorial support in the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Pediatric Nephrology, Faculty of Medicine, Toho University, 6-11-1 Omori-Nishi, Ota-Ku, Tokyo, 143-8541, Japan

    Yuko Hamasaki

  2. Department of Nephrology, Tokyo Metropolitan Children’s Medical Center, Tokyo, Japan

    Yuko Hamasaki, Kenji Ishikura, Riku Hamada, Hiroshi Hataya & Masataka Honda

  3. Division of Infectious Diseases Control, Health and Welfare Bureau Health Center of Kawasaki City, Kanagawa, Japan

    Fumiyo Komaki

  4. Division of Nephrology and Rheumatology, National Center for Child Health and Development, Tokyo, Japan

    Kenji Ishikura

  5. Department of Pediatrics, Shiga University of Medical Science, Shiga, Japan

    Tomoyuki Sakai

  6. Department of Pathology, Tokyo Metropolitan Children’s Medical Center, Tokyo, Japan

    Kentaro Ogata

  7. Department of Data Management, Japan Clinical Research Support Unit, Tokyo, Japan

    Takashi Ando

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  1. Yuko Hamasaki
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Corresponding author

Correspondence to Yuko Hamasaki.

Ethics declarations

All clinical data and follow-up information were retrospectively obtained from the medical records. The design and execution of this study were in accordance with the ethical standards of the Declaration of Helsinki. The ethics committee at Tokyo Metropolitan Children’s Medical Center approved this study (approval number: 24–28).

Funding

Yuko Hamasaki has received a research grant from Novartis Pharma and a CPCF Research Grant, 2013.

Conflict of interest

Yuko Hamasaki has received research grant from Novartis Pharma, and lecture fees from Novartis Pharma and Astellas Pharma. Kenji Ishikura has received lecture fees from Novartis Pharma, Asahi Kasei Pharma, Chugai pharmaceutical Co. Ltd. and Zenyaku Kogyo. Kenji Ishikura has also received a consultant fee from Ono pharmaceutical. Masataka Honda has received lecture fees from Novartis Pharma, Takeda Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., Zenyaku Kogyo, Pfizer Japan and Asahi Kasei Pharma. Riku Hamada has received lecture fees from Chugai Pharmaceutical Co. Ltd. Takashi Ando has received consultancy fees for statistical analyses from Asahi Kasei Pharma. The other authors have no potential conflicts of interest to disclose.

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Hamasaki, Y., Komaki, F., Ishikura, K. et al. Nephrotoxicity in children with frequently relapsing nephrotic syndrome receiving long-term cyclosporine treatment. Pediatr Nephrol 32, 1383–1390 (2017). https://doi.org/10.1007/s00467-017-3641-4

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  • DOI: https://doi.org/10.1007/s00467-017-3641-4

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