RAGE and the pathogenesis of chronic kidney disease

The multiligand receptor of the immunoglobulin superfamily, receptor for advanced glycation endproducts (RAGE), is a signal transduction receptor that binds advanced glycation endproducts, certain members of the S100/calgranulin family of proteins, high mobility group box 1 (HMGB1), advanced oxidation protein products, and amyloid (beta-sheet fibrils). Initial studies investigating the role of RAGE in renal dysfunction focused on diabetes. However, RAGE also has roles in the pathogenesis of renal disorders that are not associated with diabetes, such as obesity-related glomerulopathy, doxorubicin-induced nephropathy, hypertensive nephropathy, lupus nephritis, renal amyloidosis, and ischemic renal injuries. Experiments that have employed transgenic mouse models, pharmacological blockade of RAGE, or genetic deletion or modification of RAGE indicate that modulation of RAGE expression or function affects the functional and pathological properties of these nephropathies. Accumulating evidence links RAGE to the pathogenesis of nephropathies, indicating that antagonism of RAGE might be a strategy for the treatment of chronic kidney disease.