title: Sialylation of urinary prothrombin fragment 1 is implicated as a contributory factor in the risk of calcium oxalate kidney stone formation.
abstract: Urinary glycoproteins are important inhibitors of calcium oxalate crystallization and adhesion of crystals to renal cells, both of which are key mechanisms in kidney stone formation. This has been attributed to glycosylation of the proteins. In South Africa, the black population rarely form stones (incidence < 1%) compared with the white population (incidence 12-15%). A previous study involving urinary prothrombin fragment 1 from both populations demonstrated superior inhibitory activity associated with the protein from the black group. In the present study, we compared N-linked and O-linked oligosaccharides released from urinary prothrombin fragment 1 isolated from the urine of healthy and stone-forming subjects in both populations to elucidate the relationship between glycosylation and calcium oxalate stone pathogenesis. The O-glycans of both control groups and the N-glycans of the black control samples were significantly more sialylated than those of the white stone-formers. This demonstrates a possible association between low-percentage sialylation and kidney stone disease and provides a potential diagnostic method for a predisposition to kidney stones that could lead to the implementation of a preventative regimen. These results indicate that sialylated glycoforms of urinary prothrombin fragment 1 afford protection against calcium oxalate stone formation, possibly by coating the surface of calcium oxalate crystals. This provides a rationale for the established roles of urinary prothrombin fragment 1, namely reducing the potential for crystal aggregation and inhibiting crystal-cell adhesion by masking the interaction of the calcium ions on the crystal surface with the renal cell surface along the nephron.
authors.affiliation: Department of Chemistry, University of Cape Town, South Africa.
authors.forename: Dawn
authors.initials: D
authors.lastname: Webber
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Radcliffe
authors.forename: Louise
authors.initials: L
authors.lastname: Royle
authors.forename: Gemma
authors.initials: G
authors.lastname: Tobiasen
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Merry
authors.forename: Allen L
authors.initials: AL
authors.lastname: Rodgers
authors.forename: Edward D
authors.initials: ED
authors.lastname: Sturrock
authors.forename: Mark R
authors.initials: MR
authors.lastname: Wormald
authors.forename: David J
authors.initials: DJ
authors.lastname: Harvey
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Dwek
authors.forename: Pauline M
authors.initials: PM
authors.lastname: Rudd
mesh_terms: D000328:Adult; D000368:Aged; D044383:Black People; D002129:Calcium Oxalate / Q000378:metabolism*; D004198:Disease Susceptibility; D006031:Glycosylation; D006801:Humans; D007669:Kidney Calculi / Q000208:ethnology / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D009844:Oligosaccharides / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry* / Q000652:urine*; D011134:Polysaccharides / Q000737:chemistry; D011498:Protein Precursors / Q000737:chemistry* / Q000652:urine*; D011516:Prothrombin / Q000737:chemistry* / Q000652:urine*; D012306:Risk; D012307:Risk Factors; D012794:Sialic Acids / Q000737:chemistry*; D044465:White People
chemical_list: D009844:Oligosaccharides; D010446:Peptide Fragments; D011134:Polysaccharides; D011498:Protein Precursors; D012794:Sialic Acids; D002129:Calcium Oxalate; C029733:prothrombin fragment 1; D011516:Prothrombin