Nephrotic syndrome: components, connections, and angiopoietin-like 4-related therapeutics.
Nephrotic syndrome is recognized by the presence of proteinuria in excess of 3.5 g/24 h along with hypoalbuminemia, edema, hyperlipidemia (hypertriglyceridemia and hypercholesterolemia), and lipiduria. Each component has been investigated individually over the past four decades with some success. Studies published recently have started unraveling the molecular basis of proteinuria and its relationship with other components. We now have improved understanding of the threshold for nephrotic-range proteinuria and the pathogenesis of hypertriglyceridemia. These studies reveal that modifying sialylation of the soluble glycoprotein angiopoietin-like 4 or changing key amino acids in its sequence can be used successfully to treat proteinuria. Treatment strategies on the basis of fundamental relationships among different components of nephrotic syndrome use naturally occurring pathways and have great potential for future development into clinically relevant therapeutic agents.
Glomerular Disease Therapeutics Laboratory, University of Alabama at Birmingham, Birmingham, Alabama.
Camille
C
Macé
Glomerular Disease Therapeutics Laboratory, University of Alabama at Birmingham, Birmingham, Alabama chugh@uab.edu.
Sumant S
SS
Chugh
D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000235:genetics* / Q000378:metabolism*; D015195:Drug Design; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009404:Nephrotic Syndrome / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism
C474772:ANGPTL4 protein, human; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; D019158:N-Acetylneuraminic Acid
FSGS; diabetic nephropathy; lipids; nephrotic syndrome; podocyte; proteinuria