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Title: Early response to immunosuppressive therapy predicts good renal outcome in lupus nephritis: Lessons from long-term followup of patients in the Euro-Lupus Nephritis Trial
Authors: Houssiau, Frédéric A
Vasconcelos, Carlos
D'Cruz, David
Sebastiani, Gian Domenico
de Ramon Garrido, Enrique
Danieli, Maria Giovanna
Abramovicz, Daniel
Blockmans, Daniel Engelbert
Mathieu, Alessandro
Direskeneli, Haner
Galeazzi, Mauro
Gül, Ahmet
Levy, Yair
Petera, Peter
Popovic, Rajko
Petrovic, Radmila
Sinico, Renato Alberto
Cattaneo, Roberto
Font, Josep
Depresseux, Geneviève
Cosyns, Jean-Pierre
Cervera, Ricard #
Issue Date: 2004
Publisher: Annals of the Rheumatic Diseases
Host Document: vol:63 issue:11 pages:111-112
Conference: EULAR 2004 location:Berlin, Germany date:9-12 June 2004
Abstract: Background: In a prospective trial (the Euro-Lupus Nephritis Trial [ELNT]), we randomly assigned 90 lupus patients with proliferative glomerulonephritis to a high-dose (HD) intravenous (IV) cyclophosphamide (CYC) regimen (6 monthly pulses and 2 quarterly pulses; doses increased according to white blood cell count nadir) or a low-dose (LD) IV CYC regimen (6 fortnightly pulses at a fixed dose of 500 mg), each of which was followed by azathioprine (AZA). After a median of 41.3 months (M), we did not observe a different efficacy between the two regimens (Houssiau et al. A&R 2002; 46: 2121). The purpose of the current analysis is to extend the follow-up and to identify pronostic factors.Methods: Follow-up data were collected from all patients randomized in the ELNT, except 5 who were lost to follow-up. Survival curves were derived using the Kaplan-Meier (KM) method. Patients were classified in two groups (poor or good long-term renal outcome) according to the development (or not) of permanent renal impairment at last follow-up (defined as a serum creatinine value repeatedly ≥ 1.4 mg/dl). Their baseline characteristics and early response to therapy were compared.Results: After a mean (± SD) follow-up of 68 ± 18 M, the KM analyses indicated that there was no significantly greater cumulative probability of end-stage renal disease (ESRD), doubling of serum creatinine (DSC) or death in patients given a LD IV CYC regimen. At long-term follow-up, 18 patients (8 LD and 10 HD) had suffered from permanent renal impairment (ESRD, DSC or impaired renal function but without reaching DSC). Their baseline mean serum creatinine was significantly higher (p = 0.03) than that measured in patients with good long-term renal outcome. Interestingly, their initial response after 3 M and 6 M of therapy was much less favourable. Thus, mean (g ± SD) 24-h proteinuria, dropped from 3.03 ± 2.49 at baseline to 1.48 ± 1.28 at 3 M and to 1.15 ± 1.41 at 6 M in patients with good renal outcome, while it remained high in the poor renal outcome group, from 3.23 ± 2.25 at baseline to 3.59 ± 3.80 at 3M (p = 0.001 vs good outcome group) and to 2.55 ± 2.68 at 6 M (p = 0.007). The percentage of patients who reduced their 24-h proteinuria by at least 75% at 6 month was significantly higher in the good long-term renal outcome group (52% vs 18%, p = 0.02). The positive predictive value of a 75% drop in 24-h proteinuria at 6 M for a good long-term renal outcome was 90%.Conclusion: Long-term follow-up of patients randomized in the ELNT confirms that a remission-inducing regimen of LD IV CYC followed by AZA achieves clinical results comparable to those obtained with a HD regimen. Interestingly, an early dramatic reduction of 24-h proteinuria is highly predictive of a good long-term renal outcome.
Publication status: published
KU Leuven publication type: IMa
Appears in Collections:Laboratory for Clinical Infectious and Inflammatory Disorders
# (joint) last author

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