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)