title: Reduction in mean glomerular pore size coincides with the development of large shunt pores in patients with diabetic nephropathy.
abstract: The glomerular size selectivity was determined by neutral dextran clearance sieving technique and plasma cystatin C levels in two groups of patients with long-standing type I diabetes mellitus and different stages of albuminuria but normal glomerular filtration rate and in a group of healthy controls. The sieving characteristics of the glomerular filter were determined using a mathematical model of log normal pore size distribution. Patients with albuminuria above 200 microg/min exhibited a significant increase of cystatin c plasma concentrations and a significant reduction in mean glomerular filtration slit size. Only these patients exhibited large, unrestrictive pores in the glomerular filter (shunt). The plasma cystatin c levels correlated significantly with 26-angstrom neutral dextran plasma levels in microalbuminuric patients and in patients with albuminuria above 200 microg/min. We conclude that a reduction in average pore size of the glomerular filter does not occur earlier than the development of large shunt pores. The renal clearance of cystatin c in patients with proteinuric diabetic nephropathy but a normal glomerular filtration rate is reduced due to its molecular size.
authors.affiliation: Department of Internal Medicine III, Division of Nephrology and Dialysis, University of Vienna, Austria. rainer.oberbauer@akh-wien.ac.at
authors.forename: R
authors.initials: R
authors.lastname: Oberbauer
authors.forename: V
authors.initials: V
authors.lastname: Nenov
authors.forename: C
authors.initials: C
authors.lastname: Weidekamm
authors.forename: M
authors.initials: M
authors.lastname: Haas
authors.forename: T
authors.initials: T
authors.lastname: Szekeres
authors.forename: G
authors.initials: G
authors.lastname: Mayer
mesh_terms: D000328:Adult; D000419:Albuminuria / Q000097:blood; D055316:Cystatin C; D015891:Cystatins / Q000097:blood; D003911:Dextrans / Q000097:blood / Q000493:pharmacokinetics; D003928:Diabetic Nephropathies / Q000097:blood / Q000378:metabolism* / Q000652:urine; D005260:Female; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010539:Permeability
chemical_list: C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D003911:Dextrans