Chapter 25 - Systemic Lupus Erythematosus and the Kidney

Abstract

Kidney involvement in systemic lupus erythematosus, termed lupus nephritis (LN), occurs in 50% to 75% of lupus patients and is a significant cause of lupus-associated morbidity and mortality, including end-stage kidney disease. LN is a paradigm of immune complex–mediated kidney injury: The immune deposits that incite LN are primarily complexes of anti-double-stranded DNA antibodies directed against nucleosomal antigens. However, the pathogenesis is complex, involving abnormalities in multiple components of the immune system, including B and T cells, the complement cascade, cytokines, and clearance of apoptosis. The diagnosis of LN is suspected by changes in laboratory parameters—elevated serum creatinine, presence of hematuria and/or proteinuria, low serum complement levels—but still hinges on the kidney biopsy with glomerular changes being the major determinant of classification. The current approach to treating LN is guided by histologic findings (i.e., International Society of Nephrology (ISN)/Renal Pathology Society (RPS) class and the degree of activity and chronicity), with appropriate consideration of presenting clinical parameters and the degree of kidney function impairment. Treatment regimens for LN typically utilize combination therapy of corticosteroids with cyclophosphamide or mycophenolate. After remission is obtained, maintenance therapy involves a tapering dose of corticosteroids combined with an antimetabolite. LN has been shown to impact clinical outcomes in systemic lupus erythematosus (SLE) both directly via target organ damage and indirectly through complications of therapy.