HDCN Article Review/Hyperlink

Dooley MA, Hogan S, Jennette C, Falk R for the Gloremular Disease Collaborative Network

Cyclophosphamide therapy for lupus nephritis: poor renal survival in black Americans

Kidney Int (Apr) 51:1188-1195 1997

The glomerular disease collaborative network (GDCN) reports outcomes in 89 pts (58 black, 31 white) using cyclophosphamide therapy for SLE with diffuse proliferative glomerulonephritis (DPGN). Since 1985, patients with a renal biopsy diagnosis of SLE-DPGN from over 200 nephrologists in the southeastern United States (GDCN) treated with intravenous cyclophosphamide (IV CYC) were treated with IV-CYC once monthly for six months at a dose of 0.5 to 1.0 gram per meter square adjusted to the patient's nadir white blood cell count with subsequent IV cyclophosphamide q 3 months. Oral prednisone was started at 60 mg per day for two months and tapered. Beginning in 1989, IV methylprednisolone was given at a dose of 7 mg/ kg/ day for 3 days at the of biopsy. One renal pathologist reviewed all biopsies.

Endpoints were renal survival, with time to ESRD requiring dialysis or transplantation. Retrospective review of clinical data was performed on each patient and Kaplan-Meier survival curves and Cox's proportional hazards models were performed for analysis of data. Most patients had normal serum creatinine at the time of entry into the study. Because there were only 3 deaths prior to ESRD, overall patient survival was not calculated. Overall renal survival was 89% at one year, 86% at two years, 81% at three years, 75% at four years and 71% at five years. Age, sex, SLE duration, entry serum creatinine level, presence of uncontrolled hypertension, and treatment with IV methylprednisolone did not predict renal survival. The sum of activity and chronicity scores was an important predictor for ESRD, patients with a combined score > 14 being more likely to progress. Renal survival for non-blacks was 94.5% at 9 months and stayed at that level for 5 years, whereas renal survival in blacks was 85% at 9 months and declined to 57% at 5 years (P=.007). Importantly, biopsy findings could not predict the development of ESRD in black patients.

As expected, the 8 patients with serum creatinine > 3.0 on entry into the study were more likely to reach ESRD compared to those with better renal function. Neither the absolute blood pressure nor degree of BP control affected progression of renal disease, and no difference related to the type of antihypertensive agent was noted. The cumulative dose and duration of immunosuppressives were lower in blacks only because therapy was discontinued following development of ESRD.

Comment: Different from other clinical trials was the inclusion of patients in the registry at the time of renal biopsy so that the early course of SLE-DPGN was reported. It is clear that there is a group of black patients who rapidly progresses to ESRD despite no differences in clinical, laboratory or pathologic features when compared to white patients. Neither immunosuppressive therapy nor blood pressure control prevented progression in this set of patients. Though it has previously been shown that black patients are more likely to have worse renal survival, this study contradicts previous data suggesting that serum creatinine at the time of initiation of treatment is the most important variable in predicting renal survival. Because the authors did not anticipate finding these racial differences, further data such as socio-economic status or medical insurance information was not obtained. Further studies that include an age matched control group of black vs. white patients as well as more extensive epidemiologic investigation will be necessary to elucidate the cause for these racial differences in renal survival. (N. Kevin Krane, M.D., Tulane University School of Medicine)