Class IV-S versus class IV-G lupus nephritis: clinical and morphologic differences suggesting different pathogenesis.
BACKGROUND
A recently proposed reclassification of lupus nephritis divides class IV (diffuse proliferative) lupus nephritis into those cases with predominantly segmental proliferative lesions (class IV-S) and those with predominantly global proliferative lesions (class IV-G). This report explores the validity of this distinction and possible differences in pathogenesis between the 2 types of lesions.


METHODS
Patients from a previously reported series of severe lupus nephritis, with initial biopsies (Bx1) and control biopsies (Bx2) at 6 months after induction therapy were reclassified according to the newly proposed classification. From the original series of 65 patients, 15 patients were reclassified as having class IV-S lesions and 31 patients class IV-G lesions. Clinical data at both biopsies and follow-up were available on all patients selected.


RESULTS
Patients with IV-G lesions had worse proteinuria, lower serum hemoglobins, lower CH50s, and likely higher SCrs (P = .06) and lower C3s (P = .08) than class IV-S patients. Serum CH50 and C3 correlated negatively with severity of class IV-G lesions, but not at all with class IV-S lesions. Patients with class IV-G lesions had greater overall immune deposits and subendothelial deposits on IF and greater hyaline deposits on light microscopy. By contrast, class IV-S showed predominant mesangial deposits and a much higher rate of glomerular fibrinoid necroses (13.3 +/- 15.3% vs. 5.6 +/- 8.0% of viable glomeruli, P = .03). Other distinctions included the fact that membranoproliferative features were found only in class IV-G lesions, and glomerular monocyte/macrophages were much more frequent in this group than in class IV-S lesions (1.77 +/- 0.92 vs. 0.86 +/- 0.77, P = .008). Finally, class IV-G frequently involved all viable glomeruli (74.2% of cases), whereas segmental proliferative lesions never did (P < .0001). Survivals from doubling of SCr at 10 years did not differ between the 2 types at Bx1: 72.5% segmental versus 60.4% global, P= .53. However, among those with persistent lesions at Bx 2 (11 IV-S and 9 IV-G), there was a dramatic difference in 10-year survivals between IV-S lesions (63.6%) and IV-G lesions (0%), P = .08.


CONCLUSIONS
There are definite clinical and morphologic differences between class IV-S and IV-G lesions. Data suggest that class IV-G lesions behave as an immune complex disease, having positive correlations with extent of immune deposits and negative correlations with serum complement levels, the model traditionally assumed for lupus nephritis as a whole. However, in class IV-S lesions, the presence of proportionally greater glomerular fibrinoid necroses and lack of correlation with extent of immune deposits suggest that these lesions may have a different pathogenesis.
Hill
Gary S
GS
Hôpital Européen Georges Pompidou, and INSERM Unité 652, Paris, France. garyhillparis@aol.com
Delahousse
Michel
M
Nochy
Dominique
D
Bariéty
Jean
J
D000328:Adult; D000936:Antigen-Antibody Complex / Q000378:metabolism; D001706:Biopsy; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D007678:Kidney Glomerulus / Q000473:pathology*; D008181:Lupus Nephritis / Q000145:classification* / Q000401:mortality / Q000473:pathology*; D008264:Macrophages / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000473:pathology; D009336:Necrosis; D012008:Recurrence; D016019:Survival Analysis
D000936:Antigen-Antibody Complex; D003404:Creatinine