title: Albuminuria associated with CD2AP knockout mice is primarily due to dysfunction of the renal degradation pathway processing of filtered albumin.
abstract: Here we address the assumption that the massive intact albuminuria accompanying mutations of structural components of the slit diaphragm is due to changes in glomerular permeability. The increase in intact albumin excretion rate in Cd2ap knockout mice by >100-fold was not accompanied by equivalent changes in urine flow rate, glomerular filtration rate or increases in dextran plasma clearance rate, which demonstrates that changes in glomerular permeability alone could not account for the increase in intact albumin excretion. The albuminuria could be accounted for by inhibition of the tubule degradation pathway associated with degrading filtered albumin. There are remarkable similarities between these results and all types of podocytopathies in acquired and toxin-induced renal disease, and nephrotic states seen in mice with podocyte mutations.
authors.affiliation: SalAqua Inc, Suite 277, 331 W 57th St, New York, NY 10019, United States.
authors.forename: Leileata M
authors.initials: LM
authors.lastname: Russo
authors.forename: Subhashini
authors.initials: S
authors.lastname: Srivatsan
authors.forename: Matthew
authors.initials: M
authors.lastname: Seaman
authors.forename: Hani
authors.initials: H
authors.lastname: Suleiman
authors.forename: Andrey S
authors.initials: AS
authors.lastname: Shaw
authors.forename: Wayne D
authors.initials: WD
authors.lastname: Comper
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics*; D000419:Albuminuria / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D003598:Cytoskeletal Proteins / Q000172:deficiency / Q000235:genetics*; D005260:Female; D005919:Glomerular Filtration Rate; D007674:Kidney Diseases / Q000378:metabolism* / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010539:Permeability; D059748:Proteolysis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C114545:CD2-associated protein; D003598:Cytoskeletal Proteins
keywords: Albumin degradation; Albuminuria; Glomerular permeability; Transgenic mice