PMC4159074_01
The pathogenic stages of lupus nephritis (LN) as a guide to therapy. Systemic lupus erythematosus and LN (upper boxes) occur in patients with a genetic predisposition to autoimmunity and presumably an environmental trigger to initiate disease (stage 0). Because these patients cannot be identified with accuracy in the general population, there currently are no therapies (lower boxes) that can be applied at this stage. After initiation, autoimmunity develops as the pathogenic processes listed under stage 1 occur. This would be an ideal point to intervene with drugs that target these pathways, such as B- and T-cell-directed therapies, but patients usually do not have clinical manifestations during stage 1 and the disease is relatively silent. Kidney involvement reaches clinical attention during stage 2, and clinical manifestations are due primarily to inflammatory processes initiated within the kidney (shown in the stage 2 box, above the dotted line). The induction therapy of LN therefore must control inflammation. In addition to intrarenal inflammation, the autoimmune processes of stage 1 likely are still active and kidney-specific autoimmunity may be developing (stage 2 box, below the dotted line). Thus, in addition to anti-inflammatory therapy, the antiautoimmune therapies that were applied to stage 1 also can be used in stage 2. These therapies would contribute less to controlling inflammation, but ideally would prevent further LN flares. Active inflammation also can lead to scarring of the kidneys. Addition of an antifibrotic agent, especially if interstitial fibrosis or glomerulosclerosis were confirmed by biopsy or novel biomarker, could stabilize kidney function and decrease the rate of chronic kidney disease progression. Abbreviation: IFNalpha, interferon alpha.
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