Elsevier

The American Journal of Medicine

Volume 119, Issue 4, April 2006, Pages 355.e25-355.e33
The American Journal of Medicine

Clinical research study
Long-term Outcome of Diffuse Proliferative Lupus Glomerulonephritis Treated with Cyclophosphamide

https://doi.org/10.1016/j.amjmed.2005.08.045Get rights and content

Abstract

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.

Section snippets

Study Population

Between 1988 and 2002, all patients with renal biopsy-proven diffuse proliferative lupus glomerulonephritis (Class IV nephritis according to the revised 1995 WHO classification15) treated in 5 regional hospitals of Hong Kong were identified from either the hospital clinical registries or the pathologists’ renal biopsy databases. All patients had to fulfill at least 4 of the American College of Rheumatology (ACR) criteria for the classification of SLE.9 Those patients who were treated initially

Demographic Data and Baseline Renal Parameters

A total of 268 patients with diffuse proliferative lupus nephritis confirmed by renal biopsy were identified. Two hundred twelve patients (188 women, 24 men) were initially treated with prednisolone and CYC. All were ethnic Chinese. The mean age was 30.9 ± 10.9 years, and the mean SLE duration was 36.7 ± 55.1 months. At the time of renal biopsy, 70% of patients were nephrotic, 37% had impaired serum creatinine level (>106 umol/L), and 34% were hypertensive (blood pressure ≥140/90 mmHg). The

Discussion

This is a retrospective review of the long-term outcome of a very large cohort of patients with DPLN treated initially with prednisolone and CYC and followed prospectively in 5 regional hospitals of Hong Kong. As CYC protocols being used and the monitoring strategies for patients are similar in these centers, longitudinal data are available for analysis. Using the hospital clinical and pathology registries, we believe that we have nested all the patients within the specified period to minimize

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