The pathology of lupus nephritis

An international working group of clinicians and pathologists met in 2003 under the auspices of the International Society of Nephrology (ISN) and the Renal Pathology Society (RPS) to revise and update the 1982 and 1995 World Health Organization classification of lupus glomerulonephritis. This article compares and contrasts the ISN/RPS classification and the antecedent World Health Organization classifications. Although systemic lupus erythematosus is the prototypical systemic immune-complex disease, several non-immune-complex mechanisms of glomerular injury and dysfunction have been proposed, and this article summarizes the evidence supporting the pathogenic mechanisms of lupus vasculitis, glomerular capillary thrombosis, and lupus podocytopathy. The most significant and controversial feature of the ISN/RPS classification is the separation of diffuse glomerulonephritis into separate classes with either segmental (class IV-S) or global (class IV-G) lesions. Several groups have tested the prognostic significance of this separation, and this article discusses the implications of these studies for the ISN/RPS classification.