Outcome and prognostic indicators of diffuse proliferative lupus glomerulonephritis treated with sequential oral cyclophosphamide and azathioprine.
OBJECTIVE
To study the outcome and prognostic indicators of diffuse proliferative glomerulonephritis (DPGN) in patients with systemic lupus erythematosus (SLE) treated with sequential oral cyclophosphamide (CYC) and azathioprine (AZA).


METHODS
SLE patients with biopsy-proven DPGN treated with sequential oral CYC and AZA were studied. Those who achieved renal remission at 12 months were identified, and the clinical predictors of complete remission were evaluated by regression analysis. All patients were followed up until a relapse of the nephritis or a doubling of the serum creatinine level occurred. The timing and risk factors for flares and creatinine doubling were evaluated by Kaplan-Meier analysis and with the Cox proportional hazards model.


RESULTS
We studied 55 patients (47 women, 8 men; mean +/- SD age at renal biopsy 31.1 +/- 10.4 years); 25 (46%) had a serum creatinine level >106 micromoles/liter, and 29 (53%) had nephrotic syndrome. At 12 months posttreatment, 37 (67%) had complete remission and 12 (22%) had partial remission. The initial serum creatinine level was an independent predictor of complete remission. Excluding the 4 patients who were treatment- resistant or died, 21 patients (41%) had renal flares during a median followup of 4 years. The cumulative risk of renal flare was 6% at 1 year, 21% at 3 years, and 32% at 5 years. The median time to relapse was 43 months. The histologic activity score and the mean daily dose of CYC were multivariate predictors of renal flare, by Cox regression. At the last followup visit, 9 of 54 patients (17%) had a doubling of the creatinine level, 6 of whom (11%) underwent dialysis. The cumulative risk of creatinine doubling was 8.4% at 5 years and 18.2% at 10 years. An increasing chronicity index at the time of initial renal biopsy was an independent predictor of deterioration in renal function.


CONCLUSIONS
Sequential therapy with oral CYC followed by AZA appears to be an effective treatment regimen for DPGN in patients with SLE, with 89% of patients achieving complete or partial remission at 12 months, 62.8% remaining in remission after 5 years, and 81.8% having stable renal function after 10 years. Predictors of treatment resistance and relapse include increasing serum creatinine level, higher histologic activity scores, and a lower dose of CYC. Increasing chronicity indices predict a deterioration of renal function.
Mok
Chi Chiu
CC
Queen Mary Hospital, Pokfulam, Hong Kong. ccmok@netvigator.com
Ho
Carmen Tze Kwan
CT
Chan
Kwok Wah
KW
Lau
Chak Sing
CS
Wong
Raymond Woon Sing
RW
D000284:Administration, Oral; D000328:Adult; D001379:Azathioprine / Q000008:administration & dosage*; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008181:Lupus Nephritis / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D015995:Prevalence; D011379:Prognosis; D012008:Recurrence; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D001379:Azathioprine