Long-term effects of cyclophosphamide therapy in steroid-dependent or frequently relapsing idiopathic nephrotic syndrome.
BACKGROUND
It has been demonstrated that alkylating agents such as cyclophosphamide (CYP) are effective in reducing the risk of relapse in frequently relapsing (FRNS) and steroid-dependent nephrotic syndrome (SDNS). Little is known about prognostic factors in SDNS and FRNS treated by CYP. The objectives of this study are to determine long-term outcomes and factors associated with sustained remission in these patients.


METHODS
We retrospectively studied the data from 143 children (104 boys) with SDNS and FRNS treated with CYP in six centres over 15 years. Relapse-free survival was estimated by Kaplan-Meier method. The determinants of long-term remission were assessed by univariate and multivariate analyses using Cox proportional hazard models.


RESULTS
Median age at diagnosis was 3.7 years (interquartile range: IQR 2.3-5.9), and median follow-up was 7.8 years (IQR 4.0-11.8). CYP treatment was introduced after a median time of 1.7 years (IQR 0.7-5.9) after diagnosis. Patients received a median cumulative dose of 168 mg/kg (IQR 157-197) body weight. Relapse-free survival was 65%, 44%, 27% and 13% after 6 months, 1 year, 2 years and 5 years, respectively. In multivariate analysis, sustained remission >2 years was associated with age at treatment >5 years (P = 0.02) and cumulative dose of CYP >170 mg/kg (P = 0.02). Frequently relapsing versus steroid-dependent status and female gender were predictors of borderline significance. Height and body mass index standard deviation score were significantly influenced by CYP treatment.


CONCLUSIONS
In our study, long-term efficacy of cyclophosphamide in steroid-responsive nephrotic syndrome is disappointing. Further well-designed trials are required to evaluate the efficacy of other steroid-sparing agents.
Cammas
Benoît
B
Centre Hospitalier Universitaire de Bordeaux, Service de Pédiatrie, Centre de référence Maladies Rénales Rares du Sud Ouest, Bordeaux, France.
Harambat
Jérôme
J
Bertholet-Thomas
Aurélia
A
Bouissou
François
F
Morin
Denis
D
Guigonis
Vincent
V
Bendeddouche
Salih
S
Afroukh-Hacini
Nawel
N
Cochat
Pierre
P
Llanas
Brigitte
B
Decramer
Stéphane
S
Ranchin
Bruno
B
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D002675:Child, Preschool; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D009404:Nephrotic Syndrome / Q000188:drug therapy* / Q000473:pathology; D012008:Recurrence; D012189:Retrospective Studies; D015996:Survival Rate; D013995:Time; D013997:Time Factors; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide