Whole urinary proteins coat calcium oxalate monohydrate crystals to greatly decrease their adhesion to renal cells.
OBJECTIVE
Adhesion of urinary crystals to renal tubular cells could be a critical event that triggers a cascade of responses ending in kidney stone formation. We clarified the role of urinary macromolecules during calcium oxalate monohydrate (COM) crystal adhesion to cells.


METHODS
To assess COM crystal binding to cells in the presence of whole urine and fractions thereof we used monolayer cultures of distal nephron derived Madin-Darby canine kidney, type I cells as a model system.


RESULTS
COM crystal adhesion to cells was decreased in the presence of whole urine compared with an ultrafiltrate prepared by passing urine through a 10 kDa cutoff membrane. Supplementing the ultrafiltrate with urinary concentrate containing proteins greater than 10 kDa returned crystal adhesion to low levels, similar to whole urine. Macromolecules in whole urine acted to decrease binding to cells by coating crystals and 4 proteins previously implicated in the pathogenesis of nephrolithiasis were detected on coated crystals (bikunin, osteopontin, prothrombin fragment 1 + 2 and Tamm-Horsfall glycoprotein). Crystals precipitated and grown in whole urine also bound less avidly to cells than crystals precipitated in artificial urine.


CONCLUSIONS
This study confirms that macromolecules present in whole urine can coat crystals and, thereby, block their adhesion to renal tubular cells. Preventing crystal retention in the kidney could be an important mechanism whereby these macromolecules protect against kidney stones.
Kumar
Vivek
V
Department of Medicine, Division of Nephrology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Farell
Gerard
G
Lieske
John C
JC
D000328:Adult; D002129:Calcium Oxalate / Q000737:chemistry*; D002448:Cell Adhesion; D002478:Cells, Cultured; D003460:Crystallization; D006023:Glycoproteins / Q000737:chemistry / Q000652:urine*; D006801:Humans; D007684:Kidney Tubules / Q000166:cytology*; D046911:Macromolecular Substances; D008297:Male; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000652:urine; D009088:Mucoproteins / Q000737:chemistry; D053495:Osteopontin; D010446:Peptide Fragments / Q000737:chemistry / Q000652:urine; D011498:Protein Precursors / Q000737:chemistry / Q000652:urine; D011516:Prothrombin / Q000737:chemistry / Q000652:urine; D012795:Sialoglycoproteins / Q000737:chemistry / Q000652:urine; D014360:Trypsin Inhibitor, Kunitz Soybean; D014462:Ultrafiltration; D014556:Urine / Q000737:chemistry*; D058949:Uromodulin
D006023:Glycoproteins; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D009088:Mucoproteins; D010446:Peptide Fragments; D011498:Protein Precursors; C109148:SPINT2 protein, human; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C548612:UMOD protein, human; D058949:Uromodulin; D053495:Osteopontin; D002129:Calcium Oxalate; C029733:prothrombin fragment 1; C044183:prothrombin fragment 2; D011516:Prothrombin; D014360:Trypsin Inhibitor, Kunitz Soybean