Long-term outcome of diffuse proliferative lupus glomerulonephritis treated with cyclophosphamide

Am J Med. 2006 Apr;119(4):355.e25-33. doi: 10.1016/j.amjmed.2005.08.045.


Purpose: 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.

MeSH terms

  • Administration, Oral
  • Adult
  • Amenorrhea / chemically induced
  • Analysis of Variance
  • Anti-Inflammatory Agents / therapeutic use
  • China
  • Cyclophosphamide / administration & dosage*
  • Cyclophosphamide / adverse effects*
  • Drug Therapy, Combination
  • Female
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / adverse effects*
  • Injections, Intravenous
  • Logistic Models
  • Lupus Nephritis / drug therapy*
  • Lupus Nephritis / pathology*
  • Male
  • Ovary / drug effects
  • Prednisolone / therapeutic use
  • Prognosis
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Failure
  • Treatment Outcome


  • Anti-Inflammatory Agents
  • Immunosuppressive Agents
  • Cyclophosphamide
  • Prednisolone