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Erschienen in: Pediatric Nephrology 7/2008

01.07.2008 | Original Article

Long-term follow-up after cyclophosphamide and cyclosporine-A therapy in steroid-dependent and -resistant nephrotic syndrome

verfasst von: Viktória Sümegi, Ibolya Haszon, Csaba Bereczki, Ferenc Papp, Sándor Túri

Erschienen in: Pediatric Nephrology | Ausgabe 7/2008

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Abstract

A retrospective study was made on 37 children with idiopathic nephrotic syndrome (INS). At the beginning, all patients were steroid sensitive but received more than one steroid course (median 4). Following several relapses, they became steroid dependent or steroid resistant. Group 1 consisted of 22 children [3 focal segmental glomerulosclerosis (FSGS), 19 minimal-change NS (MCNS)] who received cyclophosphamide (CP) orally for 2.5 ± 0.5 months. Group 2 consisted of 15 children (7 FSGS, 8 MCNS) who received cyclosporine-A (CSA) for 28 ± 15 months. The level of proteinuria decreased significantly and remained low during the follow-up. The relapse-free period was significantly longer in the CP group (CP 30 ± 21.5; CSA 26.2 ± 18 months, p < 0.001). The relapse rate decreased significantly in both groups and remained in this lower level during the follow-up (from 3.4 ± 2.8 to 0.1 ± 0.2/year in group 1, and from 3.7 ± 3.1 to 0.6 ±  0.8/year in group 2). At the end of the 5-year follow-up, 20/22 patients (90.9%) and 10/15 patients (66.6%) were in remission in groups 1 and 2 respectively, with or without treatment (p < 0.05). In the long term, both CP and CSA is effective second-line therapy following steroid monotherapy in INS patients, but the relapse rate was lower and the relapse free period was significantly longer in the CP-treated group.
Literatur
1.
Zurück zum Zitat Ehrich JH, Brodehl J (1991) Long versus standard prednisolone therapy for initial treatment of idiopathic nephrotic syndrome in children (Arbeitsgemeinschaft für Padiatrische Nephrologie). Eur J Pediatr 150:380–387CrossRef Ehrich JH, Brodehl J (1991) Long versus standard prednisolone therapy for initial treatment of idiopathic nephrotic syndrome in children (Arbeitsgemeinschaft für Padiatrische Nephrologie). Eur J Pediatr 150:380–387CrossRef
2.
Zurück zum Zitat Abeyagunawardena AS, Dillon MJ, Rees L, van’t Hoff W, Trompeter RS (2003) The use of steroid-sparing agents in steroid-sensitive nephrotic syndrome. Pediatr Nephrol 18:919–924CrossRefPubMed Abeyagunawardena AS, Dillon MJ, Rees L, van’t Hoff W, Trompeter RS (2003) The use of steroid-sparing agents in steroid-sensitive nephrotic syndrome. Pediatr Nephrol 18:919–924CrossRefPubMed
3.
Zurück zum Zitat Sümegi V, Haszon I, Ivanyi B, Bereczki Cs, Papp F, Turi S (2004) Long-term effects of levamisole treatment in childhood nephrotic syndrome. Pediatr Nephrol 19:1354–1360CrossRefPubMed Sümegi V, Haszon I, Ivanyi B, Bereczki Cs, Papp F, Turi S (2004) Long-term effects of levamisole treatment in childhood nephrotic syndrome. Pediatr Nephrol 19:1354–1360CrossRefPubMed
4.
Zurück zum Zitat Report of a workshop by the British Association for Paediatric Nephrology and Research Unit, Royal College of Physicians (1994) Consensus statement on management and audit potential for steroid responsive nephrotic syndrome. Arch Dis Child 71:151–157CrossRef Report of a workshop by the British Association for Paediatric Nephrology and Research Unit, Royal College of Physicians (1994) Consensus statement on management and audit potential for steroid responsive nephrotic syndrome. Arch Dis Child 71:151–157CrossRef
5.
Zurück zum Zitat Bircan Z, Kara B (2003) Intravenous cyclophosphamide is the drug of choice for steroid dependent nephrotic syndrome. Pediatr Int 45:65–67CrossRefPubMed Bircan Z, Kara B (2003) Intravenous cyclophosphamide is the drug of choice for steroid dependent nephrotic syndrome. Pediatr Int 45:65–67CrossRefPubMed
6.
Zurück zum Zitat Chisthi AS, Solof 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 38:754–760CrossRef Chisthi AS, Solof 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 38:754–760CrossRef
8.
Zurück zum Zitat Zietse R, Derkx FH, Schalekamp MA, Weimar W (1995) Cyclosporine and the glomerular filtration barrier in minimal change disease and membranous nephropathy. Contrib Nephrol 114:6–18CrossRefPubMed Zietse R, Derkx FH, Schalekamp MA, Weimar W (1995) Cyclosporine and the glomerular filtration barrier in minimal change disease and membranous nephropathy. Contrib Nephrol 114:6–18CrossRefPubMed
9.
Zurück zum Zitat Borel JF, Feurer C, Gubler HU, Stahelin H (1994) Biological effects of cyclosporine A: A new antilymphocytic agent. 1976. Agents Actions 43:179–186CrossRefPubMed Borel JF, Feurer C, Gubler HU, Stahelin H (1994) Biological effects of cyclosporine A: A new antilymphocytic agent. 1976. Agents Actions 43:179–186CrossRefPubMed
10.
Zurück zum Zitat Abramowicz M, Barnett HL, Edelmann CM Jr, Greifer I, Kobayashi O, Arneil GC, Barron BA, Gordillo-P G, Hallman N, Tiddens HA (1970) Controlled trial of azathioprine in children with nephrotic syndrome. A report for the international study of kidney disease in children. Lancet 1:959–961CrossRefPubMed Abramowicz M, Barnett HL, Edelmann CM Jr, Greifer I, Kobayashi O, Arneil GC, Barron BA, Gordillo-P G, Hallman N, Tiddens HA (1970) Controlled trial of azathioprine in children with nephrotic syndrome. A report for the international study of kidney disease in children. Lancet 1:959–961CrossRefPubMed
11.
Zurück zum Zitat Hogg RJ, Furth S, Lemley KV, Portman R, Schwartz GJ, Coresh J, Balk E, Lau J, Levin A, Kausz AT, Eknoyan G, Levey AS; National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (2003) National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative clinical practice guidelines for chronic kidney disease in children and adolescents: evaluation, classification, and stratification. Pediatrics 111:1416–1421PubMed Hogg RJ, Furth S, Lemley KV, Portman R, Schwartz GJ, Coresh J, Balk E, Lau J, Levin A, Kausz AT, Eknoyan G, Levey AS; National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (2003) National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative clinical practice guidelines for chronic kidney disease in children and adolescents: evaluation, classification, and stratification. Pediatrics 111:1416–1421PubMed
12.
Zurück zum Zitat Hamahira K, Iijima K, Tanaka R, Nakamura H, Yoshikawa N (2001) Recovery from cyclosporine-associated arteriolopathy in childhood nephrotic syndrome. Pediatr Nephrol 16:723–727CrossRefPubMed Hamahira K, Iijima K, Tanaka R, Nakamura H, Yoshikawa N (2001) Recovery from cyclosporine-associated arteriolopathy in childhood nephrotic syndrome. Pediatr Nephrol 16:723–727CrossRefPubMed
13.
Zurück zum Zitat Lijima K, Hamahira K, Tanaka R, Kobayashi A, Nozu K, Nakamura H, Yoshikawa H (2002) Risk factors for cyclosporine-induced tubulointerstitial lesions in children with minimal change nephrotic syndrome. Kidney Int 61:1801–1805CrossRef Lijima K, Hamahira K, Tanaka R, Kobayashi A, Nozu K, Nakamura H, Yoshikawa H (2002) Risk factors for cyclosporine-induced tubulointerstitial lesions in children with minimal change nephrotic syndrome. Kidney Int 61:1801–1805CrossRef
14.
Zurück zum Zitat McCrory WW, Shibuya M, Lu WH, Lewy JE (1973) Therapeutic and toxic effects observed with different dosage programs of cyclophosphamide in treatment of steroid-responsive but frequently relapsing nephrotic syndrome. J Pediatr 82:614–618CrossRefPubMed McCrory WW, Shibuya M, Lu WH, Lewy JE (1973) Therapeutic and toxic effects observed with different dosage programs of cyclophosphamide in treatment of steroid-responsive but frequently relapsing nephrotic syndrome. J Pediatr 82:614–618CrossRefPubMed
15.
Zurück zum Zitat Ponticelli C, Edefonti A, Ghio L, Rizzoni G, Rinaldi S, Gusmano R, Lama G, Zacchello G, Confalonieri R, Altieri P, Bettinelli A, Maschio G, Cinotti GA, Fuiano G, Schena FP, Castellani A, Della Casa-Alberighi O (1993) Cyclosporine versus cyclophosphamide for patients with steroid-dependent and frequently relapsing idiopathic nephrotic syndrome: a multicentre randomized controlled trial. Nephrol Dial Transplant 8:1326–1332PubMed Ponticelli C, Edefonti A, Ghio L, Rizzoni G, Rinaldi S, Gusmano R, Lama G, Zacchello G, Confalonieri R, Altieri P, Bettinelli A, Maschio G, Cinotti GA, Fuiano G, Schena FP, Castellani A, Della Casa-Alberighi O (1993) Cyclosporine versus cyclophosphamide for patients with steroid-dependent and frequently relapsing idiopathic nephrotic syndrome: a multicentre randomized controlled trial. Nephrol Dial Transplant 8:1326–1332PubMed
16.
Zurück zum Zitat Niaudet P (1992) Comparison of cyclosporine and chlorambucil in the treatment of steroid-dependent idiopathic nephrotic syndrome: a multicentre randomized controlled trial. The French Society of Paediatric Nephrology. Pediatr Nephrol 6:1–3CrossRefPubMed Niaudet P (1992) Comparison of cyclosporine and chlorambucil in the treatment of steroid-dependent idiopathic nephrotic syndrome: a multicentre randomized controlled trial. The French Society of Paediatric Nephrology. Pediatr Nephrol 6:1–3CrossRefPubMed
17.
Zurück zum Zitat Pena A, Bravo J, Melgosa M, Fernandez C, Meseguer C, Espinosa L, Alonso A, Navarro M (2007) Steroid-resistant nephritic syndrome: long-term evolution after sequential therapy. Pediatr Nephrol 22:1875–1880CrossRefPubMed Pena A, Bravo J, Melgosa M, Fernandez C, Meseguer C, Espinosa L, Alonso A, Navarro M (2007) Steroid-resistant nephritic syndrome: long-term evolution after sequential therapy. Pediatr Nephrol 22:1875–1880CrossRefPubMed
18.
Zurück zum Zitat Grupe WE, Heymann W (1966) Cytotoxic drugs in steroid-resistant renal disease. Alkylating and antimetabolic agents in the treatment of nephrotic syndrome, lupus nephritis, chronic glomerulonephritis, and purpura nephritis in children. Am J Dis Child 112:448–458CrossRefPubMed Grupe WE, Heymann W (1966) Cytotoxic drugs in steroid-resistant renal disease. Alkylating and antimetabolic agents in the treatment of nephrotic syndrome, lupus nephritis, chronic glomerulonephritis, and purpura nephritis in children. Am J Dis Child 112:448–458CrossRefPubMed
19.
Zurück zum Zitat Querfeld U, Waldherr R, Scharer K (1985) The significance of focal global sclerosis in idiopathic nephratic nephrotic syndrome. Long-term clinical observations. Acta Paediatr Scand 74:913–919CrossRefPubMed Querfeld U, Waldherr R, Scharer K (1985) The significance of focal global sclerosis in idiopathic nephratic nephrotic syndrome. Long-term clinical observations. Acta Paediatr Scand 74:913–919CrossRefPubMed
20.
Zurück zum Zitat Report of the International Study Group of Kidney Disease in Children (1974) Prospective, controlled trial of cyclophosphamide therapy in children with the nephrotic syndrome. Lancet 2:423–427 Report of the International Study Group of Kidney Disease in Children (1974) Prospective, controlled trial of cyclophosphamide therapy in children with the nephrotic syndrome. Lancet 2:423–427
21.
Zurück zum Zitat Geary DF, Farine M, Thorner P, Baumal R (1984) Response to cyclophosphamide in steroid-resistant focal segmental glomerulosclerosis: a reappraisal. Clin Nephrol 22:109–113PubMed Geary DF, Farine M, Thorner P, Baumal R (1984) Response to cyclophosphamide in steroid-resistant focal segmental glomerulosclerosis: a reappraisal. Clin Nephrol 22:109–113PubMed
22.
Zurück zum Zitat Arbeitsgemeinschaft für Pädiatrische Nephrologie (1982) Effect of cytotoxic drugs in frequently relapsing nephrotic syndrome with and without steroid dependence. N Engl J Med 306:451–454CrossRef Arbeitsgemeinschaft für Pädiatrische Nephrologie (1982) Effect of cytotoxic drugs in frequently relapsing nephrotic syndrome with and without steroid dependence. N Engl J Med 306:451–454CrossRef
23.
Zurück zum Zitat Williams 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 302:929–933CrossRefPubMed Williams 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 302:929–933CrossRefPubMed
24.
Zurück zum Zitat 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 62:1102–1106CrossRef 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 62:1102–1106CrossRef
25.
Zurück zum Zitat Drummond KN, Hillman DA, Marchessault JH, Feldman W (1968) Cyclophosphamide in the nephrotic syndrome of childhood: its use in two groups of patients defined by clinical, light microscopic and immunopathologic findings. Can Med Assoc J 98:524–531PubMedPubMedCentral Drummond KN, Hillman DA, Marchessault JH, Feldman W (1968) Cyclophosphamide in the nephrotic syndrome of childhood: its use in two groups of patients defined by clinical, light microscopic and immunopathologic findings. Can Med Assoc J 98:524–531PubMedPubMedCentral
26.
27.
Zurück zum Zitat Rance CP, Arbus GS, Balfe JW (1976) Management of the nephrotic syndrome in children. Pediatr Clin North Am 23:735–750CrossRefPubMed Rance CP, Arbus GS, Balfe JW (1976) Management of the nephrotic syndrome in children. Pediatr Clin North Am 23:735–750CrossRefPubMed
28.
Zurück zum Zitat Dundon S, O’Callaghan U, Raftery J (1980) Stability of remission in minimal lesion nephrotic syndrome after treatment with prednisolone and cyclophosphamide. Int J Pediatr Nephrol 1:22–25PubMed Dundon S, O’Callaghan U, Raftery J (1980) Stability of remission in minimal lesion nephrotic syndrome after treatment with prednisolone and cyclophosphamide. Int J Pediatr Nephrol 1:22–25PubMed
29.
Zurück zum Zitat Griswold WR, Kaufman DB, Smith FG, McIntosh RM (1971) Cyclophosphamide in nephrotic syndrome. Clin Res 19:233 Griswold WR, Kaufman DB, Smith FG, McIntosh RM (1971) Cyclophosphamide in nephrotic syndrome. Clin Res 19:233
30.
Zurück zum Zitat Latta K, von Schnakenburg C, Ehrich JH (2001) A meta-analysis of cytotoxic treatment for frequently relapsing nephrotic syndrome in children. Pediatr Nephrol 16:271–282CrossRefPubMed Latta K, von Schnakenburg C, Ehrich JH (2001) A meta-analysis of cytotoxic treatment for frequently relapsing nephrotic syndrome in children. Pediatr Nephrol 16:271–282CrossRefPubMed
31.
Zurück zum Zitat Barratt TM, Soothill JF (1970) Controlled trial of cyclophosphamide in steroid-sensitive relapsing nephrotic syndrome of childhood. Lancet 2:479–482CrossRefPubMed Barratt TM, Soothill JF (1970) Controlled trial of cyclophosphamide in steroid-sensitive relapsing nephrotic syndrome of childhood. Lancet 2:479–482CrossRefPubMed
32.
Zurück zum Zitat Ghose S, Kumar M, Kundu B, Bindal S (1977) Long-term follow up of steroid and cyclophosphamide therapy in nephrosis. Indian Pediatr 14:885–889PubMed Ghose S, Kumar M, Kundu B, Bindal S (1977) Long-term follow up of steroid and cyclophosphamide therapy in nephrosis. Indian Pediatr 14:885–889PubMed
33.
Zurück zum Zitat Grushkin CM, Fine RN, Heuser E, Lieberman E (1970) Cyclophosphamide therapy of idiopathic nephrosis. Calif Med 13:1–5 Grushkin CM, Fine RN, Heuser E, Lieberman E (1970) Cyclophosphamide therapy of idiopathic nephrosis. Calif Med 13:1–5
34.
Zurück zum Zitat Cattran DC, Appel GB, Hebert LA, Hunsicker LG, Pohl MA, Hoy WE, Maxwell DR, Kunis CL (1999) A randomized trial of cyclosporine in patients with steroid-resistant focal segmental glomerulosclerosis. Kidney Int 56:2220–2226CrossRefPubMed Cattran DC, Appel GB, Hebert LA, Hunsicker LG, Pohl MA, Hoy WE, Maxwell DR, Kunis CL (1999) A randomized trial of cyclosporine in patients with steroid-resistant focal segmental glomerulosclerosis. Kidney Int 56:2220–2226CrossRefPubMed
35.
Zurück zum Zitat Durkan A, Hodson E, Willis N, Craig J (2003) Non-corticosteroid treatment for nephrotic syndrome in children (Cochrane Review) The Cochrane Library. 1. Oxford, Update Software Ltd Durkan A, Hodson E, Willis N, Craig J (2003) Non-corticosteroid treatment for nephrotic syndrome in children (Cochrane Review) The Cochrane Library. 1. Oxford, Update Software Ltd
36.
Zurück zum Zitat Kemper MJ, Kuwertz-Broeking E, Bulla M, Mueller-Wiefel DE, Neuhaus TJ (2004) Recurrence of severe steroid dependency in cyclosporin A-treated childhood idiopathic nephrotic syndrome. Nephrol Dial Transplant 19:1136–1141CrossRefPubMed Kemper MJ, Kuwertz-Broeking E, Bulla M, Mueller-Wiefel DE, Neuhaus TJ (2004) Recurrence of severe steroid dependency in cyclosporin A-treated childhood idiopathic nephrotic syndrome. Nephrol Dial Transplant 19:1136–1141CrossRefPubMed
37.
Zurück zum Zitat Ingulli E, Singh A, Baqi N, Ahmad H, Moazami S, Tejani A (1995) Aggressive, long-term cyclosporine therapy for steroid-resistant focal segmental glomerulosclerosis. J Am Soc Nephrol 5:1820–1825PubMed Ingulli E, Singh A, Baqi N, Ahmad H, Moazami S, Tejani A (1995) Aggressive, long-term cyclosporine therapy for steroid-resistant focal segmental glomerulosclerosis. J Am Soc Nephrol 5:1820–1825PubMed
38.
Zurück zum Zitat Sairam VK, Kaila A, Rajaraman S, Travis LB (2002) Secondary resistance to cyclosporin A in children with nephrotic syndrome. Pediatr Nephrol 17:842–846CrossRefPubMed Sairam VK, Kaila A, Rajaraman S, Travis LB (2002) Secondary resistance to cyclosporin A in children with nephrotic syndrome. Pediatr Nephrol 17:842–846CrossRefPubMed
39.
Zurück zum Zitat Waldo FB, Benfield MR, Kohaut EC (1998) Therapy of focal and segmental glomerulosclerosis with methylprednisolone, cyclosporine A, and prednisone. Pediatr Nephrol 12:397–400CrossRefPubMed Waldo FB, Benfield MR, Kohaut EC (1998) Therapy of focal and segmental glomerulosclerosis with methylprednisolone, cyclosporine A, and prednisone. Pediatr Nephrol 12:397–400CrossRefPubMed
Metadaten
Titel
Long-term follow-up after cyclophosphamide and cyclosporine-A therapy in steroid-dependent and -resistant nephrotic syndrome
verfasst von
Viktória Sümegi
Ibolya Haszon
Csaba Bereczki
Ferenc Papp
Sándor Túri
Publikationsdatum
01.07.2008
Verlag
Springer Berlin Heidelberg
Erschienen in
Pediatric Nephrology / Ausgabe 7/2008
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-008-0771-8

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