Skip to main content

Nephrotoxicity of once-daily cyclosporine A in minimal change nephrotic syndrome

Pediatric Nephrology volume 27, pages 671–674 (2012)Cite this article

Abstract

Background

Although once-daily cyclosporine (CsA) therapy may have greater nephrotoxic-sparing effects than standard twice-daily therapy, little information is available in children with steroid-dependent minimal change nephrotic syndrome (MCNS) regarding histological analysis after long-term once-daily administration.

Case-Diagnosis/Treatment

A prospective study of the clinical efficacy and comparison between pre- and post-treatment renal biopsy findings in ten children (mean age, 8.8 years) with steroid-dependent MCNS who were administered once-daily CsA therapy for more than 24 months (mean ± SD, 30 ± 3.7) was performed in Saitama Children’s Medical Center. Administration of once-daily CsA therapy (mean dose, 2.8 ± 0.6 mg/kg/day; mean C2 levels, 670 ± 64 ng/ml) resulted in a significant reduction in the median relapse rate from 4.6 to 0.2 times per year, and five patients did not experience a relapse of NS. Furthermore, mean threshold of prednisolone dose significantly reduced from 1.2 to 0.02 mg/kg on alternate days. However, two patients showed evidence of chronic CsA nephrotoxicity (CsAN).

Conclusions

Once-daily CsA therapy appears to be effective in children with steroid-dependent MCNS. However, follow-up renal biopsies should be performed to investigate the presence of CsAN after more than 24 months of treatment with once-daily regimen as well as with the conventional twice-daily regimen.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

  1. Ishikura K, Yoshikawa N, Hattori S, Sasaki S, Iijima K, Nakanishi K, Matsuyama T, Yata N, Ando T, Honda M (2010) Treatment with microemulsified cyclosporine in children with frequently relapsing nephrotic syndrome. Nephrol Dial Transplant 25:3956–3962

    PubMed  Article  CAS  Google Scholar 

  2. Iijima K, Hamahira K, Tanaka R, Kobayashi A, Nozu K, Nakamura H, Yoshikawa N (2002) Risk factors for cyclosporine-induced tubulointerstitial lesions in children with minimal change nephrotic syndrome. Kidney Int 61:1801–1805

    PubMed  Article  Google Scholar 

  3. Fujinaga S, Kaneko K, Muto T, Ohtomo Y, Murakami H, Yamashiro Y (2006) Independent risk factors for chronic cyclosporine induced nephropathy in children with nephrotic syndrome. Arch Dis Child 91:666–670

    PubMed  Article  CAS  Google Scholar 

  4. Fujinaga S, Ohtomo Y, Someya T, Shimizu T, Yamashiro Y, Kaneko K (2008) Is single-daily low-dose cyclosporine therapy really effective in children with idiopathic frequent-relapsing nephrotic syndrome? Clin Nephrol 69:84–89

    PubMed  CAS  Google Scholar 

  5. International Study of Kidney Disease in Children (1978) Nephrotic syndrome in children: prediction of histopathology from clinical and laboratory characteristics at time of diagnosis. A report of the International Study of Kidney Disease in Children Kidney Int 13:159–165

    Google Scholar 

  6. Schwartz GJ, Haycock GB, Edelmann CM Jr, Spitzer A (1976) A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 58:259–263

    PubMed  CAS  Google Scholar 

  7. Mihatsch MJ, Antonovych T, Bohman SO, Habib R, Helmchen U, Noel LH, Olsen S, Sibley RK, Kemény E, Feutren G (1994) Cyclosporin A nephropathy: standardization of the evaluation of kidney biopsies. Clin Nephrol 41:23–32

    PubMed  CAS  Google Scholar 

  8. Hulton SA, Neuhaus TJ, Dillon MJ, Barratt TM (1994) Long-term cyclosporine A treatment of minimal-change nephrotic syndrome of childhood. Pediatr Nephrol 8:401–403

    PubMed  Article  CAS  Google Scholar 

  9. Takeda A, Ohgushi H, Niimura F, Matsutani H (1998) Long-term effects of immunosuppressants in steroid-dependent nephrotic syndrome. Pediatr Nephrol 12:746–750

    PubMed  Article  CAS  Google Scholar 

  10. Suzuki K, Oki E, Tsuruga K, Aizawa-Yshiro T, Ito E, Tanaka H (2010) Benefits of once-daily administration of cyclosporin A for children with steroid-dependent, relapsing nephrotic syndrome. Tohoku J Exp Med 220:183–186

    PubMed  Article  CAS  Google Scholar 

  11. Tanaka H, Tsugawa K, Tsuruga K, Shimada J, Suzuki K, Ito E (2006) Single-dose daily treatment with cyclosporine A for relapsing nephrotic syndrome: report of a case showing poor response. Clin Nephrol 66:219–220

    PubMed  CAS  Google Scholar 

  12. Ruggenenti P, Perico N, Mosconi L, Gaspari F, Benigni A, Amuchastegui CS, Bruzzi I, Remuzzi G (1993) Calcium channel blockers protect transplant patients from cyclosporine-induced daily renal hypoperfusion. Kidney Int 43:706–711

    PubMed  Article  CAS  Google Scholar 

  13. Bianco PD, Silva HT Jr, Boni R, Machado PG, Pacheco-Silva A, Pestana JO (2002) Cyclosporine from twice to single daily dosing: impact on renal function, mortality, and graft loss. Transplant Proc 34:2920–2921

    PubMed  Article  CAS  Google Scholar 

  14. Tanaka H, Tsugawa K, Suzuki K, Ito E (2006) Renal biopsy findings in children receiving long-term treatment with cyclosporine a given as a single daily dose. Tohoku J Exp Med 209:191–196

    PubMed  Article  CAS  Google Scholar 

Download references

Author information

Affiliations

  1. Division of Nephrology, Saitama Children’s Medical Center, 2100 Magome, Iwatsuki-ward, Saitama-city Saitama, 339 8551, Japan

    Shuichiro Fujinaga & Daishi Hirano

  2. Division of Pathology, Saitama Children’s Medical Center, Saitama, Japan

    Hitohiko Murakami

  3. Department of Pediatrics, Juntendo Nerima Hospital, Tokyo, Japan

    Yoshiyuki Ohtomo

  4. Department of Pediatrics, Juntendo University School of Medicine, Tokyo, Japan

    Toshiaki Shimizu

  5. Department of Pediatrics, Kansai Medical University, Osaka, Japan

    Kazunari Kaneko

Authors
  1. Shuichiro Fujinaga
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daishi Hirano
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hitohiko Murakami
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yoshiyuki Ohtomo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Toshiaki Shimizu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kazunari Kaneko
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shuichiro Fujinaga.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Fujinaga, S., Hirano, D., Murakami, H. et al. Nephrotoxicity of once-daily cyclosporine A in minimal change nephrotic syndrome. Pediatr Nephrol 27, 671–674 (2012). https://doi.org/10.1007/s00467-011-2076-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-011-2076-6

Keywords

  • Once-daily cyclosporine therapy
  • Chronic cyclosporine nephrotoxicity
  • Minimal change nephrotic syndrome