Pathogenesis and treatment of systemic lupus erythematosus nephritis.
OBJECTIVE
Glomerulonephritis is a challenging complication of systemic lupus erythematosus that still results in kidney loss in up to 30% of patients. In this review we highlight the development of integrated efforts to link pathogenesis with disease definition and new therapeutics.


RESULTS
Immune complex deposition in the kidney initiates an inflammatory cascade that causes glomerular disease but there are many modulating factors including genetic predisposition, products of the innate immune system, cytokines, complement and activated cells (both renal and immune). Animal models can help dissect potential disease mechanisms but the study of multiple models will be required since there are multiple subsets of human disease. Recent therapeutic studies in humans address the distinction between therapies for remission induction and remission maintenance. Multiple studies confirm the therapeutic equivalence of mycophenolate mofetil and cyclophosphamide in induction of remission but results are still far from ideal. The next few years should see the testing of new biologic reagents in humans. Another area of interest is the search for noninvasive measures of disease and disease response.


CONCLUSIONS
Although there has been remarkable progress in our understanding of the immunology and phenotype of lupus nephritis current therapies have insufficient efficacy. As new therapies emerge, improved clinical design coupled with mechanistic studies will be needed to identify agents that may be effective only in some patient subpopulations.
Davidson
Anne
A
Departments of Medicine, Columbia University Medical Center, 1130 St. Nicholas Avenue, New York, NY 10032, USA. ad2247@columbia.edu
Aranow
Cynthia
C
D000818:Animals; D003520:Cyclophosphamide / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008181:Lupus Nephritis / Q000188:drug therapy* / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D051379:Mice; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D012074:Remission Induction
D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D009173:Mycophenolic Acid