Cyclophosphamide in frequent-relapsing or steroid-dependent nephrotic syndrome: Review of 38 patients
Keywords:
nephrotic syndrome, frequent relapse, steroid dependent, cyclophosphamide
Abstract
Background Steroid-sensitive nephrotic syndrome (SSNS) in chil-dren is characterized by relapsing courses in a substantial propor-
tion of affected individuals. Children with frequent-relapsing neph-
rotic syndrome (FRNS) or steroid-dependent nephrotic syndrome
(SDNS) are at risk of severe steroid toxicity and need individual-
ized treatment. Previous studies have elucidated that cyclophos-
phamide (CPA) reduced the risk of relapses and increased the
length of subsequent remissions in children with relapsing SSNS.
Methods This retrospective study evaluated 38 patients (26 FRNS
and 12 SDNS) after cyclophosphamide therapy to elucidate the
efficacy of CPA in FRNS or SDNS in the Department of Child Health,
Cipto Mangunkusumo Hospital. All patients were treated with CPA
(2 mg/kg per day) for 8 weeks, in combination with prednisone.
Results The median (range) duration of follow up was 45 months
(24-140 months) for FRNS and 29 months (24-63 months) for
SDNS. The mean relapse rate one year prior to CPA therapy in
FRNS and SDNS were 3.8 relapses/year (95%CI 3.4; 4.2) and 4.0
relapses/year (95%CI 3.3; 4.7), which were reduced to 1.6 relapses/
year (95% CI 1.1; 2.1) and 2.3 relapses/year (95%CI 1.5;3.2), re-
spectively. The overall rate of cumulative sustained good response
(complete remission or infrequent relapses) was 65% after 36
months. Frequent relapsing versus steroid-dependent status was
significantly correlated with rate of sustained good response after
36 months (85% versus 15%) with OR=23 (95%CI 3.1;225.2).
Conclusion The efficacy of cyclophosphamide therapy in the
management of FRNS is better than in SDNS
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dren with steroid resistant nephrotic syndrome.
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Children. Nephrotic Syndrome in children: Prediction of
histopathology from clinical and laboratory characteris-
tics at time of diagnosis. Kidney Int 1978;13:159-65.
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MullerWiefel DE. Unfavorable response to cyclophos-
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Pediatr Nephrol 2000;14:772-5.
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Child 1990;65:1147-50.
17. Mattoo TK. Kidney biopsy prior to cyclophosphamide
therapy in primary nephrotic syndrome. Pediatr
Nephrol 1991;5:617-9.
18. Arbeitsgemeinschaft für Pädiatrische Nephrologie. Cy-
clophosphamide treatment of steroid dependent neph-
rotic syndrome: comparison of 8 week with 12 week
course. Arch Dis Child 1987;62:1102-6.
19. Ponticelli C, Edefonti A, Ghio L, Rizzoni G, Rinaldi S,
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randomized controlled trial. Nephrol Dial Transplant
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sitive nephrotic syndrome: outcome and outlook.
Pediatr Nephrol 2003;8:661-4.
21. Arbeitsgemeinschaft für Pädiatrische Nephrologie. Ef-
fect of cytotoxic drugs in frequently relapsing neph-
rotic syndrome with and without steroid dependence.
N Engl J Med 1982; 306:451-4.
22. Latta K, Schnakenburg C, Ehrich JHH. A meta-analy-
sis of cytotoxic treatment for frequently relapsing neph-
rotic syndrome in children. Pediatr Nephrol 2001;
16:271-82.
23. McCrory WW, Shibuya M, Lu WH, Lewy JE. Thera-
peutic and toxic effects observed with different dos-
age programs of cyclophosphamide in treatment of
steroid-responsive but frequently relapsing neph-
rotic syndrome. J Pediatr 1973;82:614-8.
primary nephrotic syndrome in children: Identification
of patients with minimal change nephrotic syndrome
from initial response to prednisone. J Pediatr
1981;98:561-6.
2. Barnett HL. The natural and treatment history of glom-
erular diseases in children – what can we learn from
international cooperative studies? A report of the In-
ternational Study of Kidney Disease in Children. Pre-
sented at the Sixth International Congress of Neph-
rology, Basel; 1976; Basel, Switzerland.
3. Koskimies O, Vilska J, Rapola J, Hallman N. Long-term
outcome of primary nephrotic syndrome. Arch Dis
Child 1982;57:544-8.
4. Tarshish P, Tobin JN, Bernstein J, Edelmann CMJ. Prog-
nostic significance of the early course of minimal
change nephrotic syndrome: Report of the Interna-
tional Study of Kidney Disease in Children. J Am Soc
Nephrol 1997;8:769-76.
5. Durkan AM, Hodson EM, Willis NS, Craig JC. Immu-
nosuppressive agents in childhood nephritic syndrome:
A meta-analysis of randomized controlled trial Kidney
Int 2001;59:1919-27.
6. Barrat TM, Soothill JF. Controlled trial of cyclophos-
phamide in steroid sensitive relapsing nephrotic syn-
drome of childhood. Lancet 1970;ii:479-82.
7. International Study of Kidney Disease in Children. Pro-
spective controlled trial of cyclophosphamide in chil-
dren with nephrotic syndrome. Lancet 1974;ii:423-7.
8. Wila Wirya IGN, Alatas H, Tambunan T, Khow LP,
Ramelan W. The effect of cyclophosphamide in chil-
dren with steroid resistant nephrotic syndrome.
Paediatr Indones 1976;6:291-8.
9. Alatas H. Pengobatan rasional sindrom nefrotik anak.
Presented at Simposium Penyakit Ginjal di Masyarakat,
Bandung; 1985; Bandung, Indonesia.
10. A report of the International Study of Kidney Disease in
Children. Nephrotic Syndrome in children: Prediction of
histopathology from clinical and laboratory characteris-
tics at time of diagnosis. Kidney Int 1978;13:159-65.
11. Nash MA, Edelmann Jr CM, Bernstein J, Barnett HL.
The Nephrotic Syndrome. In: Edelmann Jr CM, edi-
tor. Pediatric Kidney Disease. 2 nd ed. Boston: Little
Brown and Company; 1992. p.1247-1324.
12. Pulungan AB. Gambaran klinis dan laboratorium
sindrom nefrotik primer pada anak kelompok kambuh
sering dan dependen steroid [Thesis]. Jakarta: Bagian
Ilmu Kesehatan Anak FKUI; 1996.
13. Wila Wirya IGN. Penelitian beberapa aspek klinis dan
patologi anatomis sindrom nefrotik primer pada anak di
Indonesia [dissertation]. Jakarta: Universitas Indone-
sia; 1992.
14. Pennisi AJ, Grushkin CM, Lieberman E. Cyclophos-
phamide in the treatment of idiopathic nephrotic syn-
drome. Pediatrics 1976;57:948-51.
15. Kemper MJ, Altrogge H, Ludwig K, Timmermann K,
MullerWiefel DE. Unfavorable response to cyclophos-
phamide in steroid-dependent nephrotic syndrome.
Pediatr Nephrol 2000;14:772-5.
16. Ueda N, Kuno K, Ito S. Eight and 12 week courses of
cyclophosphamide in nephrotic syndrome. Arch Dis
Child 1990;65:1147-50.
17. Mattoo TK. Kidney biopsy prior to cyclophosphamide
therapy in primary nephrotic syndrome. Pediatr
Nephrol 1991;5:617-9.
18. Arbeitsgemeinschaft für Pädiatrische Nephrologie. Cy-
clophosphamide treatment of steroid dependent neph-
rotic syndrome: comparison of 8 week with 12 week
course. Arch Dis Child 1987;62:1102-6.
19. Ponticelli C, Edefonti A, Ghio L, Rizzoni G, Rinaldi S,
Gusmano R et al. Cyclosporin versus cyclophospha-
mide for patients with steroid dependent and frequently
relapsing idiopathic nephrotic syndrome: a multicentre
randomized controlled trial. Nephrol Dial Transplant
2003;8:1326-33.
20. Vester U, Kranz B. Cyclophosphamide in steroid-sen-
sitive nephrotic syndrome: outcome and outlook.
Pediatr Nephrol 2003;8:661-4.
21. Arbeitsgemeinschaft für Pädiatrische Nephrologie. Ef-
fect of cytotoxic drugs in frequently relapsing neph-
rotic syndrome with and without steroid dependence.
N Engl J Med 1982; 306:451-4.
22. Latta K, Schnakenburg C, Ehrich JHH. A meta-analy-
sis of cytotoxic treatment for frequently relapsing neph-
rotic syndrome in children. Pediatr Nephrol 2001;
16:271-82.
23. McCrory WW, Shibuya M, Lu WH, Lewy JE. Thera-
peutic and toxic effects observed with different dos-
age programs of cyclophosphamide in treatment of
steroid-responsive but frequently relapsing neph-
rotic syndrome. J Pediatr 1973;82:614-8.
Published
2016-10-10
How to Cite
1.
Iriani Y, Tambunan T, Sastroasmoro S. Cyclophosphamide in frequent-relapsing or steroid-dependent nephrotic syndrome: Review of 38 patients. PI [Internet]. 10Oct.2016 [cited 22Nov.2024];45(1):18-3. Available from: https://paediatricaindonesiana.org/index.php/paediatrica-indonesiana/article/view/793
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Received 2016-10-05
Accepted 2016-10-05
Published 2016-10-10
Accepted 2016-10-05
Published 2016-10-10
