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Published in: Clinical and Experimental Nephrology 2/2018

01-04-2018 | Original article

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

Authors: Yoshiyuki Kuroyanagi, Yoshimitsu Gotoh, Katsuaki Kasahara, China Nagano, Naoya Fujita, Satoshi Yamakawa, Masaki Yamamoto, Asami Takeda, Osamu Uemura

Published in: Clinical and Experimental Nephrology | Issue 2/2018

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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.
Literature
1.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
2.
go back to reference Hodson EM, Willis NS, Craig JC. Non-corticosteroid treatment for nephrotic syndrome in children. Cochrane Database Syst Rev. 2008;23:CD002290. Hodson EM, Willis NS, Craig JC. Non-corticosteroid treatment for nephrotic syndrome in children. Cochrane Database Syst Rev. 2008;23:CD002290.
3.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
4.
go back to reference Niaudet P, Reigneau O, Humbert H. A pharmacokinetic study of Neoral in childhood steroid-dependent nephrotic syndrome. Pediatr Nephrol. 2001;16:154–5.CrossRefPubMed Niaudet P, Reigneau O, Humbert H. A pharmacokinetic study of Neoral in childhood steroid-dependent nephrotic syndrome. Pediatr Nephrol. 2001;16:154–5.CrossRefPubMed
6.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
7.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
8.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
9.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
10.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
11.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
12.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
13.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
14.
go back to reference 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.CrossRef 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.CrossRef
15.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
16.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
17.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
18.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
Metadata
Title
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
Authors
Yoshiyuki Kuroyanagi
Yoshimitsu Gotoh
Katsuaki Kasahara
China Nagano
Naoya Fujita
Satoshi Yamakawa
Masaki Yamamoto
Asami Takeda
Osamu Uemura
Publication date
01-04-2018
Publisher
Springer Singapore
Published in
Clinical and Experimental Nephrology / Issue 2/2018
Print ISSN: 1342-1751
Electronic ISSN: 1437-7799
DOI
https://doi.org/10.1007/s10157-017-1444-3

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