Treatment with cyclophosphamide delays the progression of chronic lesions more effectively than does treatment with azathioprine plus methylprednisolone in patients with proliferative lupus nephritis.
OBJECTIVE
To analyze the effect of treatment with either pulse cyclophosphamide (CYC) or azathioprine (AZA) combined with methylprednisolone (MP), on serial biopsy results in patients with proliferative lupus nephritis, and to evaluate the predictive value of various histopathologic and clinical parameters with regard to disease outcome.


METHODS
Biopsy specimens from patients with proliferative lupus nephritis, obtained at study entry and after 2 years of therapy, were scored according to a standardized method, and results assessed in relation to disease outcome.


RESULTS
Of the 87 patients originally enrolled, 39 underwent repeat biopsy. These patients were representative of the overall group, both at entry and at 2-year followup. The median activity index changed from 8.0 to 2.7 (no differences between the treatment groups). In the group treated with AZA plus MP (AZA group), the increase in the median chronicity index (from 2.7 to 3.8) was larger than that in the CYC group (from 2.7 to 3.0) (P = 0.050). In multivariate analyses, renal function at enrollment and after 2 years was the best predictor of renal function at the last visit, while none of the histopathologic variables (either at entry or at 2 years) added to this prediction. Comparing patients whose disease transitioned to class II with those who had persistent proliferative lupus nephritis revealed no differences between the treatment groups at either time point, and no clinical differences at 2 years. However, a higher serum creatinine level at entry and greater proteinuria at last visit were characteristic of patients who still had proliferative lupus nephritis at 2 years.


CONCLUSIONS
These results indicate that, although both CYC and AZA are effective in reducing active lesions in lupus nephritis, progression of chronic lesions is more effectively halted by CYC. Variables assessed by repeat biopsy do not predict clinical outcome.
Grootscholten
Cecile
C
Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Bajema
Ingeborg M
IM
Florquin
Sandrine
S
Steenbergen
Eric J
EJ
Peutz-Kootstra
Carine J
CJ
Goldschmeding
Roel
R
Bijl
Marc
M
Hagen
E Christiaan
EC
Van Houwelingen
Hans C
HC
Derksen
Ronald H W M
RH
Berden
Jo H M
JH
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001379:Azathioprine / Q000627:therapeutic use*; D001706:Biopsy; D003404:Creatinine / Q000097:blood; D003520:Cyclophosphamide / Q000627:therapeutic use*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008181:Lupus Nephritis / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D015999:Multivariate Analysis; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D003404:Creatinine; D001379:Azathioprine; D008775:Methylprednisolone