Summary
In a pilot study 23 children with nephrotic syndrome were treated with cyclosporin A (Cs) for 6–45 months. 8 children suffered from steroid dependent minimal change nephrotic syndrome (MCNS) and had experienced at least one course with cytotoxic drugs, but had relapsed thereafter. 2 children had diabetes mellitus type I with nephrotic syndrome and 13 children had steroid resistant focal segmental glomerulosclerosis (FSGS). Cs was started with 100 mg/m2/day in two doses and increased stepwise to obtain a Cs whole blood trough level of 200–400 ng/ml. In steroid dependent MCNS treatment with Cs reduced relapse rate significantly, and prednisone therapy could be stopped completely. After discontinuation of Cs, relapses reoccurred as frequently as before. Renal function remained unimpaired despite repeated Cs treatment courses up to 38 months. In cases of nephrotic syndrome with diabetes type I Cs treatment led to complete remission without changing the insulin requirement. However, after discontinuation of Cs relapses reoccurred. In steroid resistant FSGS 6 children benefited from Cs treatment: 4 went into complete remission, 2 into partial remission. The 2 children with complete remission relapsed but remained Cs responsive. The remaining 7 children with FSGS did not respond to Cs but continued the course of their disease, with two patients rapidly progressing to terminal renal failure. Side-effects of Cs treatment were mild. It is concluded that Cs is an effective agent in steroid dependent MCNS and can be used as an alternative drug in specific cases like steroid toxicity or diabetes mellitus. In steroid resistant FSGS a trial with Cs seems to be warranted since some cases do respond favorably. To avoid nephrotoxicity treatment with Cs should always be monitored closely by determination of blood levels and renal function.
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Abbreviations
- MCNS:
-
minimal change nephrotic syndrome
- FSGS:
-
focal segmental glomerulosclerosis
- Cs:
-
Cyclosporin A
References
Arbeitsgemeinschaft für Pädiatrische Nephrologie (1979) Alternate-day versus intermittent prednisone in frequently relapsing nephrotic syndrome. Lancet I:401–403
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
Arbeitsgemeinschaft für Pädiatrische Nephrologie (1987) Cyclophosphamide treatment of steroid dependent nephrotic syndrome: comparison of eight weeks with 12 weeks course. Arch Dis Child 62:1102–1106
Arbeitsgemeinschaft für Pädiatrische Nephrologie (1988) Short versus standard prednisone therapy for initial treatment of idiopathic nephrotic syndrome in children. Lancet I:380–383
Arbus GS, Poucell S, Bacheyie GS, Baumal R (1982) Focal segmental glomerulosclerosis with idiopathic nephrotic syndrome: three types of clinical response. J Pediatr 101:40–45
Barnett HL, Schoeneman M, Bernstein J, Edelman CM (1978) Minimal change nephrotic syndrome. In: Edelmann CM (ed) Pediatric Kidney Disease. Little Brown, Boston, pp 695–711
Bennett WM, Norman DJ (1986) Action and toxicity of cyclosporine. Ann Rev Med 37:215–224
Borel JF, Ryffel B (1985) The mechanism of action of ciclosporin: a continuing puzzle. In: Schindler R (ed) Ciclosporin in Autoimmune Diseases. Springer, Berlin Heidelberg, pp 24–32
Brandis M, Burghard R, Leititis J, Zimmerhackl B, Hildebrandt F, Helmcher U (1987) Cyclosporine A for treatment in nephrotic syndrome. Pediatr Nephrol 1:C 42
Brodehl J, Ehrich JHH, Hoyer PF, Lee IJ, Oemar BS, Wonigeit K (1987) Cyclosporin A treatment of minimal change nephrotic syndrome and focal segmental glomerulosclerosis in children. Korean J Nephrology 6:26–33
Brodehl J, Hoyer PF (1985) Ciclosporine A treatment of idiopathic syndrome in children: minimal change disease and focal segmental glomerulosclerosis. In: Schindler R (ed) Ciclosporin in autoimmune diseases. Springer, Berlin Heidelberg, pp 329–333
Brodehl J, Krohn HP, Ehrich JHH (1982) The treatment of minimal change nephrotic syndrome (lipoidnephrosis): Cooperative studies of the Arbeitsgemeinschaft für Pädiatrische Nephrologie (APN). Klin Pädiat 194:162–165
Cameron JS, Glassock RJ (1988) Natural history and outcome of the nephrotic syndrome. In: Cameron JS, Glassock RJ (eds) The nephrotic syndrome. Marcel Dekker, New York Basel, pp 999–1033
Cameron JS, Turner DR, Ogg CS, Chantler C, Williams DG (1978) The long-term prognosis of patients with focal segmental glomerulosclerosis. Clin Nephrol 10:213–218
Capodicasa G, Desanto NG, Nuzzi F, Giordano C (1986) Cyclosperin A in nephrotic syndrome of childhood — a 14 month experience. Intern J Pediatr Nephrol 7:69–72
Donatsch P, Abisch E, Homberger M, Traber R, Trapp M, Voges RA (1981) Radioimmuno assay to measure cyclosporin A in plasma and serum samples. J Immunoassay 2:19–32
Dunnill MS (1984) Minimal change glomerulonephritis. In: Pathological basis of renal disease. Bailliere Tindall, London, pp 206–222
Feehally J, Beattle TJ, Brenchley PEC, Coupes BM, Houston IB, Mallick NP, Postlethwaite RJ (1984) Modulation of cellular immune function by cyclophosphamide in children with minimal change nephropathy. N Engl J Med 310:415–420
Fodor P, Saitua MT, Rodriguez E, Gonzalez B, Schlesinger L (1982) T-Cell dysfunction in minimal-change nephrotic syndrome of childhood. Am J Dis Child 136:713–717
Habib R, Churg J (1984) Minimal change disease, mesangial proliferative glomerulonephritis and focal sclerosis: individual entities or a spectrum of disease. In: Robinson RR (ed) Nephrology. Springer, Berlin Heidelberg New York, pp 634–644
Habib R, Gubler MC (1971) Les lesions glomerulaires focales des syndromes nephrotiques idiopathiques de l'enfant. Nephron 8:382–401
Habib R, Kleinknecht C, Royer P (1971) Le syndrome nephrotique primitif de l'enfant: classification et etude anatomo-clinique de 406 observations. Arch Franc Pediatr 28:277–319
Hoyer PF, Krull F, Brodehl J (1986) Cyclosporin in frequently relapsing minimal change nephrotic syndrome. Lancet II:335
Hoyer PF, Lee IJ, Oemar BS, Krohn HP, Offner G, Brodehl J (1988) Renal handling of uric acid under cyclosporin A treatment. Pediatr Nephrol 2:18–21
Hoyer PF, Offner G, Oemar BS, Brodehl J, Ringe B, Pichlmayr S (1988) Four years experience with cyclosporin A in pediatric kidney transplantation. Transplant Proceed 20 Suppl 3:274–279
International Study of Kidney Disease in Children (1974) Prospective controlled trial of cyclophosphamide therapy in children with the nephrotic syndrome. Lancet 2:423–427
International Study of Kidney Disease in Children (1981) The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome from initial response to prednisone. J Pediatr 98:561–564
International Study of Kidney Disease in Children (1982) Early identification of frequent relapsers among children with minimal change nephrotic syndrome. J Pediatr 101:514–518
International Study of Kidney Disease in Children (1984) Minimal change nephrotic syndrome in children: deaths during the first 5 to 15 year's observation. Pediatrics 73:497–501
Koskimies O, Vilska J, Rapola J, Hallmann N (1982) Long-term outcome of primary nephrotic syndrome. Arch Dis Child 57:544–548
Krull F, Hoyer PF, Offner G, Brodehl J (1988) Renal handling of magnesium in transplanted children under cyclosporin treatment. Eur J Pediatr (accepted)
a Lagrue C, Laurent J, Belghiti D, Robeva R (1986) Cyclosporin and idiopathic nephrotic syndrome. Lancet II:692–693
Mathew TH (1988) Nephrotic syndrome in patients with transplanted kidneys. In: Cameron JS, Glassock RJ (ed) The nephrotic syndrome. Marcel Dekker, New York Basel, pp 805–847
Meyrier A (1987) Treatment with cyclosporin of patients with idiopathic nephrotic syndrome. Springer Semin Immunopathol 9:441–450
Meyrier A, Simon P, Perret G, Condamin-Meyrier MC (1986) Remission of idiopathic nephrotic syndrome after treatment with cyclosporin A. Brit Med J 292:789–792
Mihatsch MJ, Bach JF, Coovadia HM, Forre O, Moutsopoulos HM, Drosos AA, Siamopolous KC, Noel LH, Ramsaroop R, Hällgren R, Svenson K, Bohman SO (1988) Cyclsoporin-associated nephropathy in patients with autoimmune diseases. Klin Wochenschr 66:43–47
Moncrieff MW, White RH, Ogg CS, Cameron JS (1969) Cyclophosphamide therapy in the nephrotic syndrome in childhood. Br Med J I:666–671
Niaudet P, Habib R, Tete MJ, Hinglais N, Broyer M (1987) Cyclosporin in the treatment of idiopathic nephrotic syndrome in children. Pediatr Nephrol 1:566–573
Peces R, Riera JR, Lopez Larrera C, Alvarez J (1987) Steroid-responsive relapsing nephrotic syndrome associated with early diabetic glomerulopathy in a child. Nephron 46:78–82
Shaloup RJ (1975) Pathogenesis of lipoid nephrosis: a disorder of T-cell function. Lancet II:556–560
Shoeneman MJ, Bennett B, Greifer I (1978) The natural history of focal segmental glomerulosclerosis with and without mesangial hypercellularity in children. Clin Nephrol 9:45–54
Siegel NJ, Gaudio KM, Krassner LS, McDonald BM, Anderson FP, Kashgarian M (1981) Steroid-dependent nephrotic syndrome in children: Histopathology and relapses after cyclophosphamide treatment. Kidney Intern 19:454–459
Southwest Pediatric Nephrology Study Group (1985) Focal segmental glomerulosclerosis in children with idiopathic nephrotic syndrome. Kidney Intern 27:442–449
Taube D, Brown Z, Williams DG (1984) Impaired lymphocyte and suppressor cell function in minimal change nephropathy, membranous nephropathy and focal glomerulosclerosis. Clin Nephrol 22:176–182
Tejani A, Butt K, Trachtman H, Suthanthiran M, Rosenthal CJ, Khawar MR (1987) Cyclosporine-induced remission of relapsing nephrotic syndrome in children. J Pediatr 111:1056–1062
Tejani A, Butt K, Trachtman H, Suthanthiran M, Rosenthal CJ, Khawar MR (1988) Cyclosporine A induced remission of relapsing nephrotic syndrome in children. Kidney Intern 33:729–734
Tejani A, Nicastri AD, Sen D, Chen CK, Phadke K, Adamson O, Butt KMH (1983) Long-term evaluation of children with nephrotic syndrome and focal segmental glomerular sclerosis. Nephron 35:225–231
Trompeter RS, Hicks J, Lloyd BW, White RHR, Cameron JS (1985) Long-term outcome for children with minimal change nephrotic syndrome. Lancet I:368–370
Von Graffenried B, Krupp P (1986) Side effects of cyclosporin (Sandimmun) in renal transplant recipients and in patients with autoimmune diseases. Transplant Proceed 18:876–883
Waldo FB, Kohaut EC (1987) Therapy of focal segmental glomerulosclerosis with cyclosporin. Pediatr Nephrol 1:180
Wiliams SA, Makker SP, Ingelfinger JR, Grupe WE (1980) Long-term evaluation of chlorambucil plus prednisone in the idiopathic nephrotic syndrome of childhood. N Engl J Med 302:929–933
Wish JB (1986) Immunologic effects of cyclosporine (1986) Transplant Proceed 18, Suppl 2:15–18
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Brodehl, J., Brandis, M., Helmchen, U. et al. Cyclosporin a treatment in children with minimal change nephrotic syndrome and focal segmental glomerulosclerosis. Klin Wochenschr 66, 1126–1137 (1988). https://doi.org/10.1007/BF01727848
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DOI: https://doi.org/10.1007/BF01727848