Cell biology of pathologic renal calcification: Contribution of crystal transcytosis, cell-mediated calcification, and nanoparticles

Vivek Kumar, Gerard Farell, Shihui Yu, Sean Harrington, Lorraine Fitzpatrick, Ewa Rzewuska, Virginia M. Miller, John C. Lieske

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

Introduction: The earliest lesion in the kidneys of idiopathic calcium oxalate stone formers is deposition of calcium phosphate in the interstitium, termed a Randall's plaque. Yet the cellular and molecular factors leading to their formation are unknown. Methods: The influence of urinary proteins on adhesion of preformed calcium oxalate crystals to rat continuous inner medullary collecting duct (cIMCD) cells was studied in vitro, and cIMCD cells were also exposed to calcifying media containing β-glycerophosphate for up to 28 days. Renal tissue was obtained from a stone-forming and non-stone-forming individual at the time of nephrectomy. These nanoparticles, isolated from renal stones obtained at the time of surgical resection, were analyzed and propagated in standard cell culture medium. Results: Urinary proteins influence crystal adhesion to renal epithelial cells, and this activity is abnormal in the urine of stone-forming patients. cIMCD cells assumed an osteoblastic phenotype when exposed to the calcifying medium, expressing two bone matrix proteins (osteopontin and bone sialoprotein) that were also identified in the kidney of the stone-forming patient and associated with crystal deposition. Nanoparticles were propagated from the majority of renal stones. Isolates were susceptible to selected metabolic inhibitors and antibiotics and contained conserved bacterial proteins and deoxyribonucleic acid (DNA). Conclusions: These results suggest new paradigms for Randall's plaque formation and idiopathic calcium oxalate stone disease. It seems unlikely that these events are driven solely by physical chemistry; rather, they are critically influenced by specific proteins and cellular responses, and understanding these events will provide clues toward novel therapeutic targets.

Original languageEnglish (US)
Pages (from-to)412-424
Number of pages13
JournalJournal of Investigative Medicine
Volume54
Issue number7
DOIs
StatePublished - Nov 2006

Keywords

  • Bone sialoprotein
  • Continuous inner medullary collecting duct cells
  • Nanobacteria
  • Nephrolithiasis
  • Osteopontin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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