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Cell Biology of Pathologic Renal Calcification
  1. Vivek Kumar,
  2. Gerard Farell,
  3. Shihui Yu,
  4. Sean Harrington,
  5. Lorraine Fitzpatrick,
  6. Ewa Rzewuska,
  7. Virginia M. Miller,
  8. John C. Lieske
  1. From the Division of Nephrology (V.K., G.F., S.Y., J.C.L.), Division of Endocrinology (S.H., L.F.), and Departments of Surgery and Physiology and Biomedical Engineering (E.R., V.M.M.), Mayo Clinic College of Medicine, Rochester, MN.
  1. This work was supported by grants from the National Institutes of Health (DK 53399, DK 60707, and DK 62021), The Ralph C. Wilson, Sr., and Ralph C. Wilson, Jr. Medical Research Foundation, the Oxalosis and Hyperoxaluria Foundation, and the Mayo Foundation.
  2. Presented at Experimental Biology 2006, San Francisco, CA, April 1-5, 2006.
  3. Address correspondence to: Dr. John C. Lieske, Division of Nephrology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905; e-mail: Lieske.John{at}mayo.edu.

Contribution of Crystal Transcytosis, Cell-Mediated Calcification, and Nanoparticles

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.

Key words
  • bone sialoprotein
  • continuous inner medullary collecting duct cells
  • nanobacteria
  • nephrolithiasis
  • osteopontin

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