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.
OBJECTIVE
In the Euro-Lupus Nephritis Trial (ELNT), 90 patients with lupus nephritis were randomly assigned to a high-dose intravenous cyclophosphamide (IV CYC) regimen (6 monthly pulses and 2 quarterly pulses with escalating doses) or a low-dose IV CYC regimen (6 pulses of 500 mg given at intervals of 2 weeks), each of which was followed by azathioprine (AZA). After a median followup of 41 months, a difference in efficacy between the 2 regimens was not observed. The present analysis was undertaken to extend the followup and to identify prognostic factors.


METHODS
Renal function was prospectively assessed quarterly in all 90 patients except 5 who were lost to followup. Survival curves were derived using the Kaplan-Meier method.


RESULTS
After a median followup of 73 months, there was no significant difference in the cumulative probability of end-stage renal disease or doubling of the serum creatinine level in patients who received the low-dose IV CYC regimen versus those who received the high-dose regimen. At long-term followup, 18 patients (8 receiving low-dose and 10 receiving high-dose treatment) had developed permanent renal impairment and were classified as having poor long-term renal outcome. We demonstrated by multivariate analysis that early response to therapy at 6 months (defined as a decrease in serum creatinine level and proteinuria <1 g/24 hours) was the best predictor of good long-term renal outcome.


CONCLUSIONS
Long-term followup of patients from the ELNT confirms that, in lupus nephritis, a remission-inducing regimen of low-dose IV CYC followed by AZA achieves clinical results comparable with those obtained with a high-dose regimen. Early response to therapy is predictive of good long-term renal outcome.
Houssiau
Frédéric A
FA
Université Catholique de Louvain, Brussels, Belgium. houssiau@ruma.ucl.ac.be
Vasconcelos
Carlos
C
D'Cruz
David
D
Sebastiani
Gian Domenico
GD
de Ramon Garrido
Enrique
E
Danieli
Maria Giovanna
MG
Abramovicz
Daniel
D
Blockmans
Daniel
D
Mathieu
Alessandro
A
Direskeneli
Haner
H
Galeazzi
Mauro
M
Gül
Ahmet
A
Levy
Yair
Y
Petera
Peter
P
Popovic
Rajko
R
Petrovic
Radmila
R
Sinico
Renato Alberto
RA
Cattaneo
Roberto
R
Font
Josep
J
Depresseux
Geneviève
G
Cosyns
Jean-Pierre
JP
Cervera
Ricard
R
D000293:Adolescent; D000328:Adult; D001379:Azathioprine / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007275:Injections, Intravenous; D007677:Kidney Function Tests; D008181:Lupus Nephritis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D008297:Male; D011507:Proteinuria / Q000188:drug therapy; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D001379:Azathioprine