Skip to main content
SpringerLink
Log in

Combined cyclosporine and prednisolone therapy using cyclosporine blood concentration monitoring for adult patients with new-onset minimal change nephrotic syndrome: a single-center pilot randomized trial

  • Original article
  • Published:
Clinical and Experimental Nephrology Aims and scope Submit manuscript

Abstract

Background

Minimal change nephrotic syndrome (MCNS) responds well to steroids, but some patients show frequent relapses. Long-term steroid administration leads to various adverse effects. We previously reported the effectiveness in refractory nephrosis patients of administrating microemulsified CyA (ME-CyA) once before meals and setting the target value of the CyA blood concentration at 2 h after ME-CyA administration (C2) to 600–1200 ng/ml. On this trial we evaluate the effectiveness and safety of ME-CyA for suppressing relapse of adult new-onset MCNS patients using C2 monitoring.

Methods

Adult new-onset MCNS patients were randomly allocated to a ME-CyA + prednisolone group (“CyA + PSL”) (n = 11) and a PSL-alone group (“PSL-alone”) (n = 10). The drug administration period was 18 months followed by an observation period of 12 months.

Results

The duration of remission tended to be longer in CyA + PSL with C2 >600 ng/ml than in PSL-alone (P = 0.112). The relapse rate up to 18 months was significantly lower in CyA + PSL with C2 >600 ng/ml than in PSL-alone (P = 0.02). C2 was significantly higher in the patients with no relapse at 18 months than that in the patients with relapse (P = 0.048). In CyA + PSL, the total dose of PSL was significantly reduced compared with PSL-alone (P = 0.002). Cosmetic adverse effects tended to be fewer in CyA + PSL.

Conclusions

The combination treatment regimen of ME-CyA and PSL with C2 >600 ng/ml has potential to be an important treatment option for adult new-onset MCNS patients. However, after ME-CyA dosage reduction and discontinuation, the relapse rate increased. It is thus necessary to establish a better dose-reduction method.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Faul C, Donnelly M, Merscher-Gomez S, et al. The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A. Nat Med. 2008;14(9):931–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Meyrier A. Treatment of idiopathic nephrosis by immunophilin modulation. Nephrol Dial Transplant. 2003;18(Suppl 6):vi79–86.

  3. Feutren G, Mihatsch MJ. Risk factors for cyclosporine-induced nephropathy in patients with autoimmune diseases. International Kidney Biopsy Registry of Cyclosporine in Autoimmune Diseases. N Engl J Med. 1992;326(25):1654–60.

    Article  CAS  PubMed  Google Scholar 

  4. Hamasaki Y, Yoshikawa N, Hattori S, et al. Cyclosporine and steroid therapy in children with steroid-resistant nephrotic syndrome. Pediatr Nephrol. 2009;24(11):2177–85.

    Article  PubMed  Google Scholar 

  5. Matsumoto H, Nakao T, Okada T, et al. Favorable outcome of low-dose cyclosporine after pulse methylprednisolone in japanese adult minimal-change nephrotic syndrome. Intern Med. 2004;43(8):668–73.

    Article  CAS  PubMed  Google Scholar 

  6. Eguchi A, Takei T, Yoshida T, Tsuchiya K, Nitta K. Combined cyclosporine and prednisolone therapy in adult patients with the first relapse of minimal-change nephrotic syndrome. Nephrol Dial Transplant. 2010;25(1):124–9.

    Article  CAS  PubMed  Google Scholar 

  7. Shirai S, Yasuda T, Tsuchida H, et al. Preprandial microemulsion cyclosporine administration is effective for patients with refractory nephrotic syndrome. Clin Exp Nephrol. 2009;13(2):123–9.

    Article  CAS  PubMed  Google Scholar 

  8. Mraz W, Muller C, Molnar B, Knedel M. Analysis of cyclosporin A (CsA) concentrations by fluorescence polarization immunoassay (FPIA): comparison with radio immunoassay (RIA) and liquid chromatography (HPLC). Transplant Proc. 1989;21:885–7.

    CAS  PubMed  Google Scholar 

  9. Dalere GM, Lum BL, Cooney GF, Wong-Chin M. Comparison of three methods for cyclosporine area under the curve monitoring calculations. Ther Drug Monit. 1995;17:305–7.

    Article  CAS  PubMed  Google Scholar 

  10. Radhakrishnan J, Cattran DC. The KDIGO practice guideline on glomerulonephritis: reading between the (guide)lines—application to the individual patient. Kidney Int. 2012;82(8):840–56.

    Article  PubMed  Google Scholar 

  11. Ponticelli C, Rizzoni G, Edefonti A, et al. A randomized trial of cyclosporine in steroid-resistant idiopathic nephrotic syndrome. Kidney Int. 1993;43(6):1377–84.

    Article  CAS  PubMed  Google Scholar 

  12. Tejani A, Suthanthiran M, Pomrantz A. A randomized controlled trial of low-dose prednisone and ciclosporin versus high-dose prednisone in nephrotic syndrome of children. Nephron. 1991;59(1):96–9.

    Article  CAS  PubMed  Google Scholar 

  13. Fujiwara A, Hirawa N, Kobayashi Y, et al. Efficacy of cyclosporine combination therapy for new-onset minimal change nephrotic syndrome in adults. Clin Exp Nephrol. 2015;19(2):240–6.

    Article  CAS  PubMed  Google Scholar 

  14. Vavic N, Ignjatovic L, Draskovic B, Hrvacevic R, Kovacevic Z, Paunic Z. Efficacy of therapeutic monitoring of cyclosporine through C2 and AUC(0–4) during the first 24 months following kidney transplantation. Vojnosanit Pregl. 2008;65(2):119–27.

    Article  PubMed  Google Scholar 

  15. Kusaba T, Konno Y, Hatta S, et al. More stable and reliable pharmacokinetics with preprandial administration of cyclosporine compared with postprandial administration in patients with refractory nephrotic syndrome. Pharmacotherapy. 2005;25(1):52–8.

    Article  CAS  PubMed  Google Scholar 

  16. Saito T, Iwano M, Matsumoto K, et al. Significance of combined cyclosporine-prednisolone therapy and cyclosporine blood concentration monitoring for idiopathic membranous nephropathy with steroid-resistant nephrotic syndrome: a randomized controlled multicenter trial. Clin Exp Nephrol. 2014;18(5):784–94.

    Article  CAS  PubMed  Google Scholar 

  17. Broyer M, Guest G, Gagnadoux MF. Growth rate in children receiving alternate-day corticosteroid treatment after kidney transplantation. J Pediatr. 1992;120(5):721–5.

    Article  CAS  PubMed  Google Scholar 

  18. Gipson DS, Troost JP, Lafayette RA, et al. Complete remission in the nephrotic syndrome study network. Clin J Am Soc Nephrol. 2016;11(1):81–9.

    Article  CAS  PubMed  Google Scholar 

  19. Ittel TH, Clasen W, Fuhs M, Kindler J, Mihatsch MJ, Sieberth HG. Long-term cyclosporine A treatment in adults with minimal change nephrotic syndrome or focal segmental glomerulosclerosis. Clin Nephrol. 1995;44(3):156–62.

    CAS  PubMed  Google Scholar 

  20. Meyrier A, Noel LH, Auriche P, Callard P. Long-term renal tolerance of cyclosporin A treatment in adult idiopathic nephrotic syndrome. Collaborative Group of the Societe de Dephrologie. Kidney Int. 1994;45(5):1446–56.

    Article  CAS  PubMed  Google Scholar 

  21. Yokoyama H, Sugiyama H, Narita I, Saito T, Yamagata K, Nishio S, et al. Outcomes of primary nephrotic syndrome in the elderly Japanese: retrospective analysis of the Japan Renal Biopsy Registry (J-RBR). Clin Exp Nephrol. 2015;19:496–505.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Nephrology and Hypertension, St. Marianna University School of Medicine Yokohama City Seibu Hospital, Yokohama, Kanagawa, Japan

    Sayuri Shirai & Katsuomi Matsui

  2. Department of Nephrology and Hypertension, Kawasaki Municipal Tama Hospital, Kawasaki, Kanagawa, Japan

    Naohiko Imai

  3. Department of Nephrology and Hypertension, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan

    Shina Sueki, Naoto Tominaga, Tsutomu Sakurada & Yugo Shibagaki

  4. Department of Nephrology, Kichijoji Asahi Hospital, Musashino, Tokyo, Japan

    Takashi Yasuda

  5. Department of Nephrology, JHCO Tokyo Takanawa Hospital, Takanawa, Tokyo, Japan

    Kenjiro Kimura

Authors
  1. Sayuri Shirai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Naohiko Imai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shina Sueki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Katsuomi Matsui
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Naoto Tominaga
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tsutomu Sakurada
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Takashi Yasuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kenjiro Kimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yugo Shibagaki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sayuri Shirai.

Ethics declarations

Conflict of interest

All the authors have declared no competing interest.

Human and animal rights (with IRB approval number)

This article does not contain any studies with animals performed by any of the authors.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee at which the studies were conducted (IRB approval number 1137) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Registration of clinical trials

UMIN Clinical Trials Registry number 000027185.

Informed consent

Informed consent was obtained from all individual participants included in the study.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shirai, S., Imai, N., Sueki, S. et al. Combined cyclosporine and prednisolone therapy using cyclosporine blood concentration monitoring for adult patients with new-onset minimal change nephrotic syndrome: a single-center pilot randomized trial. Clin Exp Nephrol 22, 283–290 (2018). https://doi.org/10.1007/s10157-017-1443-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10157-017-1443-4

Keywords

Search

Navigation