Long-term outcome of diffuse proliferative lupus glomerulonephritis treated with cyclophosphamide.
OBJECTIVE
To report the long-term outcome of diffuse proliferative lupus nephritis (DPLN) treated with cyclophosphamide (CYC) in Chinese patients.


METHODS
Patients with biopsy-proven DPLN treated with prednisolone and CYC were identified. The long-term renal outcome and treatment-related toxicities were reported.


RESULTS
A total of 212 patients were studied (89% women; mean age 30.9 +/- 10.9 years; mean system lupus erythematosus [SLE] duration 36.7 +/- 55.1 months). At renal biopsy, 148 (70%) patients were nephrotic, and 78 (37%) had impaired serum creatinine. One hundred and three (49%) patients received daily oral CYC, whereas 109 (51%) received intravenous bolus CYC. At last dose of CYC, 126 (59%) patients responded completely, and 56 (26%) responded partially. In a logistic regression model, the cumulative CYC dose and histologic chronicity score predicted complete response. One hundred fifty-five (73%) patients received maintenance immunosuppression for at least 3 years (88% azathioprine). After a follow-up of 1873 patient-years, 66 patients experienced renal flares, 30 had doubling of serum creatinine, 18 developed end-stage renal failure, and 14 died. The renal survival rates were 88.7%, 82.8% and 70.7% at 5, 10 and 15 years, respectively. Failure to respond completely to CYC and the absence of maintenance immunosuppression were independent predictors of a poor renal outcome. Ovarian toxicity was more frequent with the oral CYC regimen. Increasing age and higher cumulative doses of CYC were independent risk factors.


CONCLUSIONS
In Chinese patients with DPLN, the cumulative dose, rather than the route of CYC administration, determines the initial treatment response and ovarian toxicity. Maintenance immunosuppression is associated with a better long-term prognosis. The oral CYC regimen is more toxic and should be reserved for high-risk patients.
Department of Medicine, Tuen Mun Hospital, New Territories, Hong Kong, China. ccmok2005@yahoo.com
Chi Chiu
CC
Mok
King Yee
KY
Ying
Woon Leung
WL
Ng
Ka Wing
KW
Lee
Chi Hung
CH
To
Chak Sing
CS
Lau
Raymond Woon Sing
RW
Wong
Tak Cheung
TC
Au
D000284:Administration, Oral; D000328:Adult; D000568:Amenorrhea / Q000139:chemically induced; D000704:Analysis of Variance; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D002681:China; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D007275:Injections, Intravenous; D016015:Logistic Models; D008181:Lupus Nephritis / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D010053:Ovary / Q000187:drug effects; D011239:Prednisolone / Q000627:therapeutic use; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D017211:Treatment Failure; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D011239:Prednisolone