Abstract
In order to determine the long-term effects of cyclophosphamide (CPO) and to identify parameters associated with sustained remission, we retrospectively studied the data from 90 patients with steroid-dependent nephrotic syndrome (SDNS) who received a single course of oral cyclophosphamide (2 mg/kg/day for 10 to 12 weeks). The median follow-up period after CPO was 5.5 years (interquartile range 3.2–8.5). Sustained remission reached the cumulative rate of 57% at 1 year, 42% at 2 years, and 31% at 5 years. For the patients who relapsed, the median threshold dose of prednisone between CPO initiation and first relapse has significantly decreased (22.1 mg/kg/day versus 4.9 mg/kg/day, p < 0.001). No further immunosuppressive agent was required in 60% of all patients. Young age at CPO initiation was associated with a lower rate of sustained remission (p < 0.001). Age at diagnosis of nephrotic syndrome, gender, cumulative dose of CPO (in mg/kg), and level of steroid dependence at CPO initiation did not influence the outcome. The incidence of side effects was low. These findings suggest that despite the wide use of new immunosuppressive agents, a short course of CPO remains an effective second-line therapy in SDNS patients. Optimal efficiency was observed in children over 7.5 years.
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References
Hodson EM, Willis NS, Craig JC (2008) Non-corticosteroid treatment for nephrotic syndrome in children. Cochrane Database Syst Rev CD002290
Latta K, von Schnakenburg C, Ehrich JH (2001) A meta-analysis of cytotoxic treatment for frequently relapsing nephrotic syndrome in children. Pediatr Nephrol 16:271–282
Takeda A, Ohgushi H, Niimura F, Matsutani H (1998) Long-term effects of immunosuppressants in steroid-dependent nephrotic syndrome. Pediatr Nephrol 12:746–750
Barratt TM, Bercowsky A, Osofsky SG, Soothill JF (1975) Cyclophosphamide treatment in steroid-sensitive nephrotic syndrome of childhood. Lancet 1:55–58
Arbeitsgemeinschaft für Pädiatrische Nephrologie (1987) Cyclophosphamide treatment of steroid dependent nephrotic syndrome: comparison of eight week with 12 week course. Report of Arbeitsgemeinschaft für Pädiatrische Nephrologie. Arch Dis Child 62:1102–1106
Shohet I, Meyerovitch J, Aladjem M, Boichis H (1988) Cyclophosphamide in treatment of minimal change nephrotic syndrome. Eur J Pediatr 147:239–241
Ueda N, Kuno K, Ito S (1990) Eight and 12 week courses of cyclophosphamide in nephrotic syndrome. Arch Dis Child 65:1147–1150
Ponticelli C, Edefonti A, Ghio L, Rizzoni G, Rinaldi S, Gusmano R, Lama G, Zacchello G, Confalonieri R, Altieri P, Bettinelli A, Machio G, Cinotu GA, Fuiano G, Schena FP, Castellani A, Della Casa-Alberighi O (1993) Cyclosporin versus cyclophosphamide for patients with steroid-dependent and frequently relapsing idiopathic nephrotic syndrome: a multicentre randomized controlled trial. Nephrol Dial Transplant 8:1326–1332
Kemper MJ, Altrogge H, Ludwig K, Timmermann K, Muller-Wiefel DE (2000) Unfavorable response to cyclophosphamide in steroid-dependent nephrotic syndrome. Pediatr Nephrol 14:772–775
Vester U, Kranz B, Zimmermann S, Hoyer PF (2003) Cyclophosphamide in steroid-sensitive nephrotic syndrome: outcome and outlook. Pediatr Nephrol 18:661–664
Cammas B, Harambat J, Bertholet-Thomas A, Bouissou F, Morin D, Guigonis V, Bendeddouche S, Afroukh-Hacini N, Cochat P, Llanas B, Decramer S, Ranchin B (2011) Long-term effects of cyclophosphamide therapy in steroid-dependent or frequently relapsing idiopathic nephrotic syndrome. Nephrol Dial Transplant 26:178–184
Hodson EM, Craig JC, Willis NS (2005) Evidence-based management of steroid-sensitive nephrotic syndrome. Pediatr Nephrol 20:1523–1530
Watson AR, Rance CP, Bain J (1985) Long term effects of cyclophosphamide on testicular function. Br Med J Clin Res Ed 291:1457–1460
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
Berard E, Broyer M, Dehennault M, Dumas R, Eckart P, Fischbach M, Loirat C, Martinat L (2005) Corticosensitive nephrotic syndrome (or nephrosis) in children. Therapeutic guideline proposed by the Pediatric Society of Nephrology. Nephrol Ther 1:150–156
Arbeitsgemeinschaft für Pädiatrische Nephrologie (1982) Effect of cytotoxic drugs in frequently relapsing nephrotic syndrome with and without steroid dependence. N Engl J Med 306:451–454
Garin EH, Pryor ND, Fennell RS III, Richard GA (1978) Pattern of response to prednisone in idiopathic, minimal lesion nephrotic syndrome as a criterion in selecting patients for cyclophosphamide therapy. J Pediatr 92:304–308
Barratt TM, Cameron JS, Chantler C, Ogg CS, Soothill JF (1973) Comparative trial of 2 weeks and 8 weeks cyclophosphamide in steroid-sensitive relapsing nephrotic syndrome of childhood. Arch Dis Child 48:286–290
Yule SM, Boddy AV, Cole M, Price L, Wyllie R, Tasso MJ, Pearson AD, Idle JR (1996) Cyclophosphamide pharmacokinetics in children. Br J Clin Pharmacol 41:13–19
Sladek NE, Priest J, Doeden D, Mirocha CJ, Pathre S, Krivit W (1980) Plasma half-life and urinary excretion of cyclophosphamide in children. Cancer Treat Rep 64:1061–1066
Van Husen M, Kemper MJ (2011) New therapies in steroid-sensitive and steroid-resistant idiopathic nephrotic syndrome. Pediatr Nephrol doi:https://doi.org/10.1007/s00467-010-1717-5
Fakhouri F, Bocquet N, Taupin P, Presne C, Gagnadoux MF, Landais P, Lesavre P, Chauveau D, Knebelmann B, Broyer M, Grunfeld JP, Niaudet P (2003) Steroid-sensitive nephrotic syndrome: from childhood to adulthood. Am J Kidney Dis 41:550–557
Kabuki N, Okugawa T, Hayakawa H, Tomizawa S, Kasahara T, Uchiyama M (1998) Influence of age at onset on the outcome of steroid-sensitive nephrotic syndrome. Pediatr Nephrol 12:467–470
Kyrieleis HA, Levtchenko EN, Wetzels JF (2007) Long-term outcome after cyclophosphamide treatment in children with steroid-dependent and frequently relapsing minimal change nephrotic syndrome. Am J Kidney Dis 49:592–597
Barratt TM, Soothill JF (1970) Controlled trial of cyclophosphamide in steroid-sensitive relapsing nephrotic syndrome of childhood. Lancet 2:479–482
International Study of Kidney Disease in Children (1974) Prospective, controlled trial of cyclophosphamide therapy in children with nephrotic syndrome. Report of the International study of Kidney Disease in Children. Lancet 2:423–427
Niaudet P (1992) How to manage a child with steroid-responsive nephrotic syndrome when dose of prednisolone is reduced or when placed on high-dose alternate day steroids. Pediatr Nephrol 6:522
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Azib, S., Macher, M.A., Kwon, T. et al. Cyclophosphamide in steroid-dependent nephrotic syndrome. Pediatr Nephrol 26, 927–932 (2011). https://doi.org/10.1007/s00467-011-1830-0
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DOI: https://doi.org/10.1007/s00467-011-1830-0