Whole urinary proteins coat calcium oxalate monohydrate crystals to greatly decrease their adhesion to renal cells

Vivek Kumar, Gerard Farell, John C. Lieske

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Purpose: 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. Materials and 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.

Original languageEnglish (US)
Pages (from-to)221-225
Number of pages5
JournalJournal of Urology
Volume170
Issue number1
DOIs
StatePublished - Jul 1 2003

Keywords

  • Calcium oxalate
  • Kidney
  • Kidney calculi
  • Urine

ASJC Scopus subject areas

  • Urology

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