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Effectiveness and nephrotoxicity of a 2-year medium dose of cyclosporine in pediatric patients with steroid-dependent nephrotic syndrome: determination of the need for follow-up kidney biopsy

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Abstract

Background

High dose of cyclosporine (CyA) for ≥2 years in children with steroid-dependent nephrotic syndrome (SDNS) increases the risk for nephropathy. Considering this, risk can be lowered with lower doses of CyA; we evaluated the effects of a medium dose of CyA, with target serum level, C2, of 450 ng/ml, over a 2-year period of observation, to determine the need for follow-up kidney biopsy.

Methods

We retrospectively evaluated C2 levels in 38 patients (17 males, 5.2 ± 2.9 years old) with SDNS at treatment initiation, at 6, 12 and 18 months during treatment, and at the time of kidney biopsy, 2-year after treatment initiation. Fifteen patients were also treated with mizoribine or mycophenolate mofetil. A number of relapses-per-patient-per-year, relative to SDNS onset and initiation of CyA treatment, were evaluated. Serum levels of total protein, albumin and total cholesterol, blood urea nitrogen level, and the estimated glomerular filtration rate were measured at treatment initiation and at 1- and 2-year post-treatment initiation.

Results

Only one very mild case of CyA-associated nephrotoxicity was identified based on biopsy results at 2-year post-treatment initiation. C2 concentrations were maintained at 422.2 ± 133.5 ng/ml and the number of relapses decreased from 3.0 relapses-per-patient-per-year prior to CyA treatment to 0.47 relapses-per-patient-per-year after CyA treatment. No effects of the treatment on the estimated glomerular filtration rate were noted.

Conclusion

A 2-year treatment with a medium dose of cyclosporine A with or without other immunosuppressive agents is relatively safe with regard to the development of cyclosporine A nephrotoxicity.

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References

  1. El-Husseini A, El-Basuony F, Mahmoud I, Sheashaa H, Sabry A, Hassan R, Taha N, Hassan N, Sayed-Ahmad N, Sobh M. Long-term effects of cyclosporine in children with idiopathic nephrotic syndrome: a single-centre experience. Nephrol Dial Transplant. 2005;20:2433–8.

    Article  CAS  PubMed  Google Scholar 

  2. Hodson EM, Willis NS, Craig JC. Non-corticosteroid treatment for nephrotic syndrome in children. Cochrane Database Syst Rev. 2008;23:CD002290.

    Google Scholar 

  3. Durkan AM, Hodson EM, Willis NS, Craig JC. Immunosuppressive agents in childhood nephrotic syndrome: a meta-analysis of randomized controlled trials. Kidney Int. 2001;59:1919–27.

    Article  CAS  PubMed  Google Scholar 

  4. Niaudet P, Reigneau O, Humbert H. A pharmacokinetic study of Neoral in childhood steroid-dependent nephrotic syndrome. Pediatr Nephrol. 2001;16:154–5.

    Article  CAS  PubMed  Google Scholar 

  5. Eddy AA, Symons JM. Nephrotic syndrome in childhood. Lancet. 2003;362:629–39.

    Article  PubMed  Google Scholar 

  6. Hibino S, Uemura O, Nagai T, Yamakawa S, Iwata N, Ito H, Nakano M, Tanaka K. Three year outcome of childhood idiopathic nephrotic syndrome under a unified immunosuppressive protocol. Pediatr Int. 2015;57:85–91.

    Article  CAS  PubMed  Google Scholar 

  7. Iijima K, Hamahira K, Tanaka R, Kobayashi A, Nozu K, Nakamura H, Yoshikawa N. Risk factors for cyclosporine-induced tubulointerstitial lesions in children with minimal change nephritic syndrome. Kidney Int. 2002;61:1801–5.

    Article  PubMed  Google Scholar 

  8. Mahalati K, Belitsky P, Sketris I, West K, Panek R. Neoral monitoring by simplified sparse sampling area under the concentration–time curve: its relationship to acute rejection and cyclosporine nephrotoxity early after kidney transplantation. Transplantation. 1999;68:55–62.

    Article  CAS  PubMed  Google Scholar 

  9. Clase CM, Mahalati K, Kiberd BA, Lawen JG, West KA, Fraser AD, Belitsky P. Adequate early cyclosporine exposure is critical to prevent renal allograft rejection: patients monitored by absorption profiling. Am J Transplant. 2002;2:789–95.

    Article  CAS  PubMed  Google Scholar 

  10. Fujinaga S, Kaneko K, Takada M, Ohtomo Y, Akashi S, Yamashiro Y. Preprandial C2 monitoring of cyclosporine treatment in children with nephrotic syndrome. Pediatr Nephrol. 2005;20:1359–60.

    Article  PubMed  Google Scholar 

  11. Nozu K, Iijima K, Sakaeda T, Okumura K, Nakanishi K, Yoshikawa N, Honda M, Ikeda M, Matsuo M. Cyclosporine A absorption profiles in children with nephrotic syndrome. Pediatr Nephrol. 2005;20:1660–3.

    Article  PubMed  Google Scholar 

  12. Ushijima K, Uemura O, Ymada T. Age effect on whole blood cyclosporine concentrations following oral administration in children with nephrotic syndrome. Eur J Pediatr. 2012;171:663–8.

    Article  CAS  PubMed  Google Scholar 

  13. Iijima K, Sako M, Oba MS, Ito S, Hataya H, Tanaka R, Ohwada Y, Kamei K, Ishikura K, Yata N, Nozu K, Honda M, Nakamura H, Nagata M, Ohashi Y, Nakanishi K, Yoshikawa N, Japanese Study Group of Kidney Disease in Children. Cyclosporine C2 monitoring for the treatment of frequently relapsing nephrotic syndrome in children: a multicenter randomized phase II trial. Clin J Am Soc Nephrol. 2014;9:271–8.

    Article  CAS  PubMed  Google Scholar 

  14. The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome from initial response to prednisone. A report of the International Study of Kidney Disease in Children. J Pediatr. 1981;98:561–4.

    Article  Google Scholar 

  15. Uemura O, Nagai T, Ishikura K, Ito S, Hataya H, Gotoh Y, Fujita N, Akioka Y, Kaneko T, Honda M. Creatinine-based equation to estimate the glomerular filtration rate in Japanese children and adolescents with chronic kidney disease. Clin Exp Nephrol. 2014;18:626–33.

    Article  CAS  PubMed  Google Scholar 

  16. Uemura O, Nagai T, Ishikura K, Ito S, Hataya H, Gotoh Y, Fujita N, Akioka Y, Kaneko T, Honda M. Reference glomerular filtration rate levels in Japanese children: using the creatinine and cystatin C based estimated glomerular filtration rate. Clin Exp Nephrol. 2015;19:683–7.

    Article  CAS  PubMed  Google Scholar 

  17. Fujinaga S, Kaneko K, Muto T, Ohtomo Y, Murakami H, Yamashiro Y. Independent risk factors for chronic cyclosporine induced nephropathy in children with nephrotic syndrome. Arch Dis Child. 2006;91:666–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kengne-Wafo S, Massella L, Diomedi-Camassei F, Gianviti A, Vivarelli M, Greco M, Stringini GR, Emma F. Risk factors for cyclosporine A nephrotoxicity in children with steroid-dependent nephrotic syndrome. Clin J Am Soc Nephrol. 2009;4:1409–16.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Pediatric Nephrology, Department of Kidney Center, Aichi Medical University Hospital, 1-1 Yazako-Karimata, Nagakute, Aichi, 480-1195, Japan

    Yoshiyuki Kuroyanagi

  2. Department of Pediatric Nephrology, Japan Red Cross Nagoya Daini Hospital, 2-9 Myouken-cho, Shouwa-ku, Nagoya, Aichi, 466-8650, Japan

    Yoshimitsu Gotoh, Katsuaki Kasahara & China Nagano

  3. Department of Pediatric Nephrology, Aichi Children’s Health and Medical Center, 1-2 Osakata, Morioka-cho, Oobu, Aichi, 474-8710, Japan

    Naoya Fujita & Satoshi Yamakawa

  4. Department of Pediatrics, Seirei Hamamatu General Hospital, 2-12-12 Sumiyoshi, Naka-ku, Hamamatu, Shizuoka, 430-0906, Japan

    Masaki Yamamoto

  5. Department of Nephrology, Japan Red Cross Nagoya Daini Hospital, 2-9 Myouken-cho, Shouwaku, Nagoya, Aichi, 466-8650, Japan

    Asami Takeda

  6. Department of Nursing, Japanese Red Cross Toyota College of Nursing, 12-33 Nanamagari, Hakusan-cho, Toyota, Aichi, 471-8565, Japan

    Osamu Uemura

Authors
  1. Yoshiyuki Kuroyanagi
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  2. Yoshimitsu Gotoh
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  3. Katsuaki Kasahara
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  4. China Nagano
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  5. Naoya Fujita
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  6. Satoshi Yamakawa
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  7. Masaki Yamamoto
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  8. Asami Takeda
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  9. Osamu Uemura
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Corresponding author

Correspondence to Yoshiyuki Kuroyanagi.

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Conflict of interest

The authors declare that no conflict of interest exists.

Research involving human participants

All procedures involving human participants were in accordance with the ethical standards of the institution at which the studies were conducted (IRB approval number #201611 at Aichi Children’s Health and Medical Center, #1118 at the Japanese Red Cross Nagoya Daini Hospital, and #2094 at Seirei Hamamatu General Hospital) and with standards of the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Due to the retrospective nature of our study, an opt-out for informed consent was granted.

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Cite this article

Kuroyanagi, Y., Gotoh, Y., Kasahara, K. et al. Effectiveness and nephrotoxicity of a 2-year medium dose of cyclosporine in pediatric patients with steroid-dependent nephrotic syndrome: determination of the need for follow-up kidney biopsy. Clin Exp Nephrol 22, 413–419 (2018). https://doi.org/10.1007/s10157-017-1444-3

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  • DOI: https://doi.org/10.1007/s10157-017-1444-3

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