The Clinical And Pathological Study Of Diffuse Proliferative Lupus Nephritis

BackgroundDiffuse proliferative lupus nephritis is a subset of lupus nephritis with the most serious clinical manifestation and poorest prognosis. The classification of glomerulonephritis in systemic lupus erythematosus revisited by the International Society of Nephrologists and Renal Pathology Society (ISN/RPS) in2003divided Class Ⅳ (diffuse lupus nephritis) into a series of non-overlapping subcategories based on the scale of glomerular involvement and the activity or chronicity of the lesions. A diagnosis of combined class Ⅳ and class Ⅴ is established when diffuse subepithelial deposits coexist. The response to treatment and the long-term prognosis of each subcategory varied among previous studies, and there have been few studies in China to investigate the new subcategories in a large and profound scale.ObjectiveTo evaluate the clinical, histological and prognostic profiles of each subcategory of diffuse lupus nephritis based on ISN/RPS classification of lupus nephritis, and to find out the differences in response to induction treatment with corticosteroid plus cyclophosphamide of different doses between categories.MethodsPatients eligible to the study:(1) received renal biopsy in Peking Union Medical College Hospital between2002and2007, and diagnosed with Class Ⅳ or Class Ⅳ and Class Ⅴ for the first time according to ISN/RPS classification of lupus nephritis;(2) with available clinical and histologic records. The renal biopsy sections, baseline medical records and treatment and follow-up records were reviewed and analyzed for each category. Immunohistochemical staining was used to analyze the number of CD68positive cells and the area of type Ⅳ collagen in renal tissues.Results(1) The Ⅳ-G group presented more serious renal symptoms, with significantly higher baseline SCr and proteinuria than the Ⅳ-S group (P=0.009for SCr and P=0.003for proteinuria), while the systemic manifestations were similar between them. The Ⅳ-G group showed more severe proliferative lesions and inflammation, but the differences were not significant. There was no difference in5-year cumulative remission rate between the two groups, higher CTX dose showed no further benefit for both two subcategories.(2) Class Ⅳ+Ⅴ showed significantly higher baseline proteinuria than Class Ⅴ (P=0.000), while the baseline SCr and the systemic manifestations were similar between them. Class Ⅳ+Ⅴ had more CD68+cell infiltration and more type Ⅳ collagen synthesis in renal interstitium than Class Ⅳ. The5-year cumulative remission rate was significantly lower in Class IV+V than in Class IV(P=0.029), but there seemed to be a trend that higher CTX dose increased remission rate for Class Ⅳ+Ⅴ, which we didn’t see for Class Ⅳ.(3) Patients with active lesions responded better to corticosteroid plus CTX, with a remarkably higher5-year cumulative remission rate than whose with chronic or active/chronic lesions (P=0.000). High CTX dose also showed a likely benefit to improve remission rate for patients with A/C lesions.Conclusions(1) Ⅳ-G patients had more serious renal manifestations and a trend of worse histologic lesions than Ⅳ-S patients, but the prognosis was not different between the two; the active and chronic lesions showed an effective power of predicting prognosis, patients with chronic lesions had poorer prognosis; Class IV+V was worse than Class IV in both renal manifestation and prognosis.(2) Corticosteroid plus high dose CTX may improve the remission rate for patients with Class IV+V and A/C lesions.