Abstract
Cyclosporin A (CsA) has been reported to be effective as a steroid-sparing agent in frequently relapsing nephrotic syndrome (FRNS). However, low efficacy has sometimes been observed in selected patients with steroid-dependent FRNS. We speculated that a low peak level of CsA in the blood might be the cause, and conducted a prospective pilot study on such steroid-dependent FRNS patients to examine whether single-dose daily administration of CsA would yield a sufficient peak blood level, and therefore a satisfactory steroid-sparing effect. Five children with steroid-dependent FRNS, aged 7–16 years, were enrolled in the study. All had been treated with prednisolone combined with twice daily CsA (T), which was subsequently replaced with the single-dose daily administration protocol (S), because of a poor steroid-sparing effect. Although the mean daily CsA dosage with the S protocol was significantly lower than with the T protocol (S 2.4±1.1 mg/kg per day vs. T 3.6±0.8 mg/kg per day, P<0.05), the mean peak blood level tended to be higher with the S protocol than the T protocol (S 764±122 ng/ml vs. T 358±250 ng/ml, P=0.1797) without mean trough blood level elevation. As a result, the minimum dose of prednisolone required for maintenance of clinical remission tended to be lower with the S than the T protocol (S 0.4±0.2 mg/kg on alternate days vs. T 0.6±0.4 mg/kg on alternate days, P=0.0656). No evidence of CsA nephrotoxicity was observed in a repeat renal biopsy performed 9 months after commencement of the S protocol in one patient. These clinical observations, although on a small number of patients and preliminary, suggest that single-dose daily administration of CsA might be an attractive protocol in selected patients with steroid-dependent FRNS in whom CsA administration by the conventional protocol is associated with a poor steroid-sparing effect.
References
Tarshish P, Tobin JN, Bernstein J, Edelmann CM Jr (1997) Prognostic significance of the early course of minimal change nephrotic syndrome: report of the International Study of Kidney Disease in Children. J Am Soc Nephrol 8:769–776
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
Gregory MJ, Smoyer WE, Sedman A, Kershaw DB, Valentini RP, Johnson K, Bunchman TE (1996) Long-term cyclosporine therapy for pediatric nephrotic syndrome: a clinical and histologic analysis. J Am Soc Nephrol 7:543–549
Hino S, Takemura T, Okada M, Murakami K, Yagi K, Fukushima K, Yoshioka K (1998) Follow-up study of children with nephrotic syndrome treated with a long-term moderate dose of cyclosporine. Am J Kidney Dis 31:932–939
Kano K, Kyo K, Yamada Y, Ito S, Ando T, Arisaka O (1999) Comparison between pre- and posttreatment clinical and renal biopsies in children receiving low dose ciclosporine-A for 2 years for steroid-dependent nephrotic syndrome. Clin Nephrol 52:19–24
Sharma R, Kumar J, Ahmed M, Gupta A, Gulati S, Sharma AP, Bhandari M (2001) Cyclosporine level: which point estimation of drug level is the best? Transplant Proc 33:3124–3125
Citterio F, Scata MC, Borzi MT, Pozzetto U, Castagneto M (2001) C2 single-point sampling to evaluate cyclosporine exposure in long-term renal transplant recipients. Transplant Proc 33:3133–3136
Rosati A, Bertoni E, Zanazzi M, Maria LD, Ciuti R, Piperno R, Moscarelli L, Biagini M, Salvadoei M (2001) Neoral dose monitoring with cyclosporine 2-hour postdose levels (C2) in different renal transplant patient age group. Transplant Proc 33:3106–3107
Chishti AS, Sorof JM, Brewer ED, Kale AS (2001) Long-term treatment of focal segmental glomerulosclerosis in children with cyclosporine given as a single daily dose. Am J Kidney Dis 38:754–760
Tanaka H, Onodera N, Waga S (1999) Long-term azathioprine therapy in two children with steroid-dependent minimal-change nephrotic syndrome. Tohoku J Exp Med 187:273–278
Inoue Y, Iijima K, Nakamura H, Yoshikawa N (1999) Two-year cyclosporin treatment in children with steroid-dependent nephrotic syndrome. Pediatr Nephrol 13:33–39
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
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Tanaka, H., Nakahata, T. & Ito, E. Single-dose daily administration of cyclosporin A for relapsing nephrotic syndrome. Pediatr Nephrol 19, 1055–1058 (2004). https://doi.org/10.1007/s00467-004-1508-y
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00467-004-1508-y