Aggiornamento monografico
Trattamento della sindrome nefrosica idiopatica corticosensibile
CORTICOSTEROID TREATMENT OF IDIOPATHIC NEPHROTIC SYNDROME
CARLA ROMANELLO
Clinica Pediatrica, Policlinico Universitario di Udine
Novembre 2005 - pagg. 580 -586
Abstract
The steroid treatment of Idiopathic Nephrotic Syndrome (ISN) should be continued for at least
3 months, as there is evidence of an inverse correlation between the duration and the total
dosage of steroids and the risk of relapses. The tendency to relapses is a characteristic of
the natural history of ISN and only less than 10% of patients experience one attack. In contrast
with what happens in the treatment of the first episode, the intensity of the therapy during
relapses does not influence the recurrence rate. There are two initial therapeutic options
for frequent relapsing and steroid-dependent ISN: 1) repeated treatments according to the
standard therapeutic regime for relapses or 2) the discontinued prolonged corticosteroid therapy.
Well-tolerated steroid therapy can be maintained for as much as 10-15 years, without
the necessity of other drugs. Alternative therapy should be considered in the following cases:
severe adverse effects of prednisone, treatment during puberty, when the risk of steroid toxicity
is higher, major complications during severe relapses, inadequate follow-up and poor
compliance. Drugs effective in reducing the relapse rate, as demonstrated in randomised controlled
trials, are cyclophosphamide (CYC), chlorambucil (CHL), cyclosporin (CyA) and levamisole.
The latter can be considered the first choice alternative to steroids as it is well tolerated
and rarely induces adverse effects. Most authors recommend not introducing CyA
before trying CYC, as there is the possibility of definite and long-term remission with CYC.
Mycophenolate mofetil (MMF) is a promising drug, although more controlled and multicentric
trials to confirm its advantages on CyA, especially in terms of adverse effects are needed.
Classificazione MeSH
Bibliografia
1. Abramowicz M, Arneil GC, Barnett HL, et
al. Controlled trial of azathioprine in children
with nephritic syndrome. Lancet 1970; I:959-
61.
2. Arbeitsgemeinschaft fr Pdiatrische Nephrologie. Alternate-day versus intermittent prednisone in frequently relapsing nephrotic syndrome. Lancet 1979;I:401-3.
3. Arbeitsgemeinschaft fr Pdiatrische Nephrologie. Short versus standard prednisone therapy for initial treatment of idiopathic nephrotic syndrome in children. Lancet 1988; I:380-3.
4. Ehrich JHH, Brodehl J, Arbeitsgemeinschaft fr Pdiatrische Nephrologie. Long versus standard prednisone therapy for initial treatment of idiophatic nephrotic syndrome in children. Eur J Pediatr 1993;152:357-361.
5. Ueda N, Chihara M, Kawaguchi S, et al. Intermittent versus long term tapering prednisolone for initial therapy in children with idiopathic nephrotic syndrome. J Pediatr 1988; 112:122-6.
6. Ponticelli C, Passerini P. Treatment of the nephrotic syndrome associated with primary glomerulonephritis. Kidney Int 1994;46:595- 604.
7. Ksiazek J, Wyszynska T. Short versus long initial prednisone treatment in steroid-sensitive nephrotic syndrome in children. Acta Pdiatr 1995;84:889-93.
8. Hiraoka M, Tsukahara H, Matsubara K, et al. A randomised study of two long-course prednisolone regimens for nephrotic syndrome in children. Am J Kidney Dis 2003; 41(6): 1155-62.
9. Lande MB, Leonard MB. Variability among pediatric nephrologists in the initial therapy of nephrotic syndrome. Pediatr Nephrol 2000;14: 766-9.
10. Filler G. Treatment of nephrotic syndrome in children and controlled trials. Nephrol Dial Transplant 2003;18 (suppl 6): vi75-vi78.
11. Bargman MJ. Management of minimal lesion glomerulonephritis: Evidence based recommendations. Kidney Int 1999;55(70):s3- s16.
12. Hodson EM, Knight JF, Willis NS, et al. Corticosteroid therapy in nephrotic syndrome: a meta-analysis of randomized controlled trials. Arch Dis Child 2000;83:45-51.
13. Hodson EM, Knight JF, Willis NS, et al. Corticosteroid therapy for nephrotic syndrome in children. Cochrane Database Syst Rev 2004(2): CD001533.
14. Brodehl J. Conventional therapy for idiopathic nephrotic syndrome in children. Clin Nephrol 1991;35:s8-15.
15. Ekka BK, Bagga A, Srivastava RN. Single versus divided-dose prednisolone therapy for relapses of nephrotic syndrome. Pediatr Nephrol 1997;11:597-9.
16. Matoo TK, Mahmoud MA. Increased maintenance corticosteroids during upper respiratory infection decrease the risk of relapse in nephrotic syndrome. Nephron 2000; 85: 343-5.
17. Broyer M. La nphrose idiopathique de lenfant et son traitement. Arch Fran Pediar 1988; 45:1-4.
18. Durkan A, Hodson EM, Willis NS, et al. Non-corticosteroid treatment for nephrotic syndrome in children. Cochrane Database Syst Rev 2005;(2):CD002290.
19. Barratt TM, Soothill JF. Controlled trial of cyclophosphamide in steroid-sensitive relapsing nephrotic syndrome of childhood. Lancet 1970; 2:479-82.
20. Latta K, von Schnakenburg C, Ehrich JHH. A meta-analysis of citotoxic treatment for frequent relapsing nephrotic syndrome in children. Pediatr Nephrol 2001;16:271-82.
21. Standermann MB, Lilien MR, van de Kar NC, et al. Is biopsy required prior to cyclophosphamide in steroid-sensitive nephrotic syndrome? Clin Nephrol 2003;60(5):315-7.
22. Arbeitsgemeinschaft fr Pdiatrische Nephrologie. Cyclophosphamide treatment of steroid dependent nephrotic syndrome: comparison of eight week with 12 week course. Arch Dis Child 1987;62:1102-6.
23. Ueda N, Kuno K, Ito S. Eight and 12 weeks courses of cyclophosphamide in nephrotic syndrome. Arch Dis Child 1990;65:1147-50.
24. Prasad N, Gulati S, Sharma RK, et al. Pulse cyclophosphamide therapy in steroid-dependent nephrotic syndrome. Pediatr Nephrol 2004;19:494-8.
25. British Association for Paediatric Nephrology. Levamisole for corticosteroid-dependent nephrotic syndrome in childhood. Lancet 1991;337:1555-7.
26. Rashid HU, Ahmed S, Fatima N, et al. Levamisole in the treatment of steroid dependent or frequent relapsing nephrotic syndrome in children. Bangladesh Renal Journal 1996;15:6-8.
27. Weiss R. Randomized double-blind placebo controlled trial of levamisole for children with frequently relapsing/steroid dependent nephrotic syndrome. J Am Soc Nephrol 1993; 4:289.
28. Dayal U, Dayal AK, Shastry JC, et al. Use of levamisole in maintaining remission in steroidsensitive nephrotic syndrome in children. Nephron 1994;66:408-12.
29. Palcoux JB, Niaudet P, Goumy P. Side effects of levamisole in children with nephrosis. Pediatr Nephrol 1994;8:263-4.
30. Barbano G, Ginevri F, Ghiggeri GM, et al. Disseminated autoimmune disease during levamisole treatment of nephrotic syndrome. Pediatric Nephrol 1999;13:602-3.
31. Davin JC, Merkus MP. Levamisole in steroid-sensitive nephrotic syndrome of childhood: the lost paradise? Pediatr Nephrol 2005; 20:10-4.
32. Niaudet P. 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 1992;6(1):1-3.
33. Durkan A, Hodson EM, Willis NS, et al. Immunosuppressive agents in childhood nephrotic syndrome: a meta-analysis of randomized controlled trials. Kidney Int 2001; 59:1919-27.
34. Brodehl J. The treatment of minimal change nephrotic syndrome: lessons learned from multicentre co-operative studies. Europ J Pediatr 1991;150:380-7.
35. Report of a Workshop by the British Association for Paediatric Nephrology and Research Unit, Royal College of Physicians. Consensus statement on management and audit potential for steroid responsive nephrotic syndrome. Arch Dis Child 1994;70:151-7.
36. Ponticelli C, Edefonti A, Ghio L, et al. Cyclosporin versus cyclophosphamide for patients with steroid-dependent and frequently relapsing idiopathic nephrotic syndrome: a multicentre randomized controlled trial. Nephrol Dial Transplant 1993;8:1326-32.
37. Choi MJ, Eustace JA, Gimenez LF, et al. Mycophenolate mofetil treatment for primary glomerular diseases. Kidney Int 2002;61:1098- 114.
38. Briggs WA, Choi MJ, Scheel JP. Successful mycophenolate mofetil treatment of glomerular disease. Am J Kidney Dis 1998; 31(2):213-7.
39. Hogg R, Fitzgibbons L, Bruick J, et al. Multicenter trial of mycophenolate mofetil (MMF) in children with steroid dependent (SD) or frequent relapsing (FR) nephrotic syndrome (NS). Report of the Southwest Pediatric Nephrology Study Group. Nephrology Dialysis Tranplantation 2003;18 suppl 4:261.
40. Bagga A, Hari P, Moudgil A, et al. Mycophenolate mofetil and prednisolone therapy in children with steroid-dependent nephrotic syndrome. Am J Kidney Dis 2003;42(6):1114-20.
41. Ulinski T, Dubourg L, Sad MH, et al. Switch from cyclosporine A to mycophenolte mofetil in nephrotic children. Pediatr Nephrol 2005;20:482-5.
42. Gellermann J, Querfeld U. Frequently relapsing nephrotic syndrome: treatment with mycophenolate mofetil. Pediatr Nephrol 2004; 19: 101-4.
43. Barletta G-M, Smoyer WE, Bunchman TE, et al. Use of mycophenolate mofetil in steroiddependent and -resistant nephrotic syndrome. Pediatr Nephrol 2003;18:833-7.
44. Chandra M, Susin M, Abitbol C. Remission of relapsing childhood nephrotic syndrome with mycophenolate mofetil. Pediatr Nephrol 2000;14: 224-6.
45. Loeffler K, Gowrishankar M, Yiu V. Tacrolimus therapy in pediatric patients with treatment- resistant nephrotic syndrome. Pediatr Nephrol 2004;19:281-7.
46. Sinha MD, Macleod R, Rigby E, et al. Treatment of severe steroid dependent nephrotic syndrome (SDNS) in paediatrics with tacrolimus therapy. Pediatr Nephrol 2004; 19:C72.
2. Arbeitsgemeinschaft fr Pdiatrische Nephrologie. Alternate-day versus intermittent prednisone in frequently relapsing nephrotic syndrome. Lancet 1979;I:401-3.
3. Arbeitsgemeinschaft fr Pdiatrische Nephrologie. Short versus standard prednisone therapy for initial treatment of idiopathic nephrotic syndrome in children. Lancet 1988; I:380-3.
4. Ehrich JHH, Brodehl J, Arbeitsgemeinschaft fr Pdiatrische Nephrologie. Long versus standard prednisone therapy for initial treatment of idiophatic nephrotic syndrome in children. Eur J Pediatr 1993;152:357-361.
5. Ueda N, Chihara M, Kawaguchi S, et al. Intermittent versus long term tapering prednisolone for initial therapy in children with idiopathic nephrotic syndrome. J Pediatr 1988; 112:122-6.
6. Ponticelli C, Passerini P. Treatment of the nephrotic syndrome associated with primary glomerulonephritis. Kidney Int 1994;46:595- 604.
7. Ksiazek J, Wyszynska T. Short versus long initial prednisone treatment in steroid-sensitive nephrotic syndrome in children. Acta Pdiatr 1995;84:889-93.
8. Hiraoka M, Tsukahara H, Matsubara K, et al. A randomised study of two long-course prednisolone regimens for nephrotic syndrome in children. Am J Kidney Dis 2003; 41(6): 1155-62.
9. Lande MB, Leonard MB. Variability among pediatric nephrologists in the initial therapy of nephrotic syndrome. Pediatr Nephrol 2000;14: 766-9.
10. Filler G. Treatment of nephrotic syndrome in children and controlled trials. Nephrol Dial Transplant 2003;18 (suppl 6): vi75-vi78.
11. Bargman MJ. Management of minimal lesion glomerulonephritis: Evidence based recommendations. Kidney Int 1999;55(70):s3- s16.
12. Hodson EM, Knight JF, Willis NS, et al. Corticosteroid therapy in nephrotic syndrome: a meta-analysis of randomized controlled trials. Arch Dis Child 2000;83:45-51.
13. Hodson EM, Knight JF, Willis NS, et al. Corticosteroid therapy for nephrotic syndrome in children. Cochrane Database Syst Rev 2004(2): CD001533.
14. Brodehl J. Conventional therapy for idiopathic nephrotic syndrome in children. Clin Nephrol 1991;35:s8-15.
15. Ekka BK, Bagga A, Srivastava RN. Single versus divided-dose prednisolone therapy for relapses of nephrotic syndrome. Pediatr Nephrol 1997;11:597-9.
16. Matoo TK, Mahmoud MA. Increased maintenance corticosteroids during upper respiratory infection decrease the risk of relapse in nephrotic syndrome. Nephron 2000; 85: 343-5.
17. Broyer M. La nphrose idiopathique de lenfant et son traitement. Arch Fran Pediar 1988; 45:1-4.
18. Durkan A, Hodson EM, Willis NS, et al. Non-corticosteroid treatment for nephrotic syndrome in children. Cochrane Database Syst Rev 2005;(2):CD002290.
19. Barratt TM, Soothill JF. Controlled trial of cyclophosphamide in steroid-sensitive relapsing nephrotic syndrome of childhood. Lancet 1970; 2:479-82.
20. Latta K, von Schnakenburg C, Ehrich JHH. A meta-analysis of citotoxic treatment for frequent relapsing nephrotic syndrome in children. Pediatr Nephrol 2001;16:271-82.
21. Standermann MB, Lilien MR, van de Kar NC, et al. Is biopsy required prior to cyclophosphamide in steroid-sensitive nephrotic syndrome? Clin Nephrol 2003;60(5):315-7.
22. Arbeitsgemeinschaft fr Pdiatrische Nephrologie. Cyclophosphamide treatment of steroid dependent nephrotic syndrome: comparison of eight week with 12 week course. Arch Dis Child 1987;62:1102-6.
23. Ueda N, Kuno K, Ito S. Eight and 12 weeks courses of cyclophosphamide in nephrotic syndrome. Arch Dis Child 1990;65:1147-50.
24. Prasad N, Gulati S, Sharma RK, et al. Pulse cyclophosphamide therapy in steroid-dependent nephrotic syndrome. Pediatr Nephrol 2004;19:494-8.
25. British Association for Paediatric Nephrology. Levamisole for corticosteroid-dependent nephrotic syndrome in childhood. Lancet 1991;337:1555-7.
26. Rashid HU, Ahmed S, Fatima N, et al. Levamisole in the treatment of steroid dependent or frequent relapsing nephrotic syndrome in children. Bangladesh Renal Journal 1996;15:6-8.
27. Weiss R. Randomized double-blind placebo controlled trial of levamisole for children with frequently relapsing/steroid dependent nephrotic syndrome. J Am Soc Nephrol 1993; 4:289.
28. Dayal U, Dayal AK, Shastry JC, et al. Use of levamisole in maintaining remission in steroidsensitive nephrotic syndrome in children. Nephron 1994;66:408-12.
29. Palcoux JB, Niaudet P, Goumy P. Side effects of levamisole in children with nephrosis. Pediatr Nephrol 1994;8:263-4.
30. Barbano G, Ginevri F, Ghiggeri GM, et al. Disseminated autoimmune disease during levamisole treatment of nephrotic syndrome. Pediatric Nephrol 1999;13:602-3.
31. Davin JC, Merkus MP. Levamisole in steroid-sensitive nephrotic syndrome of childhood: the lost paradise? Pediatr Nephrol 2005; 20:10-4.
32. Niaudet P. 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 1992;6(1):1-3.
33. Durkan A, Hodson EM, Willis NS, et al. Immunosuppressive agents in childhood nephrotic syndrome: a meta-analysis of randomized controlled trials. Kidney Int 2001; 59:1919-27.
34. Brodehl J. The treatment of minimal change nephrotic syndrome: lessons learned from multicentre co-operative studies. Europ J Pediatr 1991;150:380-7.
35. Report of a Workshop by the British Association for Paediatric Nephrology and Research Unit, Royal College of Physicians. Consensus statement on management and audit potential for steroid responsive nephrotic syndrome. Arch Dis Child 1994;70:151-7.
36. Ponticelli C, Edefonti A, Ghio L, et al. Cyclosporin versus cyclophosphamide for patients with steroid-dependent and frequently relapsing idiopathic nephrotic syndrome: a multicentre randomized controlled trial. Nephrol Dial Transplant 1993;8:1326-32.
37. Choi MJ, Eustace JA, Gimenez LF, et al. Mycophenolate mofetil treatment for primary glomerular diseases. Kidney Int 2002;61:1098- 114.
38. Briggs WA, Choi MJ, Scheel JP. Successful mycophenolate mofetil treatment of glomerular disease. Am J Kidney Dis 1998; 31(2):213-7.
39. Hogg R, Fitzgibbons L, Bruick J, et al. Multicenter trial of mycophenolate mofetil (MMF) in children with steroid dependent (SD) or frequent relapsing (FR) nephrotic syndrome (NS). Report of the Southwest Pediatric Nephrology Study Group. Nephrology Dialysis Tranplantation 2003;18 suppl 4:261.
40. Bagga A, Hari P, Moudgil A, et al. Mycophenolate mofetil and prednisolone therapy in children with steroid-dependent nephrotic syndrome. Am J Kidney Dis 2003;42(6):1114-20.
41. Ulinski T, Dubourg L, Sad MH, et al. Switch from cyclosporine A to mycophenolte mofetil in nephrotic children. Pediatr Nephrol 2005;20:482-5.
42. Gellermann J, Querfeld U. Frequently relapsing nephrotic syndrome: treatment with mycophenolate mofetil. Pediatr Nephrol 2004; 19: 101-4.
43. Barletta G-M, Smoyer WE, Bunchman TE, et al. Use of mycophenolate mofetil in steroiddependent and -resistant nephrotic syndrome. Pediatr Nephrol 2003;18:833-7.
44. Chandra M, Susin M, Abitbol C. Remission of relapsing childhood nephrotic syndrome with mycophenolate mofetil. Pediatr Nephrol 2000;14: 224-6.
45. Loeffler K, Gowrishankar M, Yiu V. Tacrolimus therapy in pediatric patients with treatment- resistant nephrotic syndrome. Pediatr Nephrol 2004;19:281-7.
46. Sinha MD, Macleod R, Rigby E, et al. Treatment of severe steroid dependent nephrotic syndrome (SDNS) in paediatrics with tacrolimus therapy. Pediatr Nephrol 2004; 19:C72.
Corrispondenza: carla.romanello@voila.fr