Invited Review

Urological Research

, Volume 40, Issue 6, pp 623-637

First online:

Biomolecular mechanism of urinary stone formation involving osteopontin

  • Kenjiro KohriAffiliated withDepartment of Nephro-urology, Nagoya City University Graduate School of Medical Sciences Email author 
  • , Takahiro YasuiAffiliated withDepartment of Nephro-urology, Nagoya City University Graduate School of Medical Sciences
  • , Atsushi OkadaAffiliated withDepartment of Nephro-urology, Nagoya City University Graduate School of Medical Sciences
  • , Masahito HiroseAffiliated withDepartment of Nephro-urology, Nagoya City University Graduate School of Medical Sciences
  • , Shuzo HamamotoAffiliated withDepartment of Nephro-urology, Nagoya City University Graduate School of Medical Sciences
  • , Yasuhiro FujiiAffiliated withDepartment of Nephro-urology, Nagoya City University Graduate School of Medical Sciences
  • , Kazuhiro NiimiAffiliated withDepartment of Nephro-urology, Nagoya City University Graduate School of Medical Sciences
  • , Kazumi  Taguchi Affiliated withDepartment of Nephro-urology, Nagoya City University Graduate School of Medical Sciences

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Abstract

Urinary stones consist of two phases—an inorganic (mineral) phase and an organic (matrix) phase. Studies on the organic components of kidney stones have been undertaken later than those on the inorganic components. After osteopontin was identified as one of the matrix components, the biomolecular mechanism of urinary stone formation became clearer. It also triggered the development of new preventive treatments. Osteopontin expression is sporadically observed in normal distal tubular cells and is markedly increased in stone-forming kidneys. Calcium oxalate crystals adhering to renal tubular cells are incorporated into cells by the involvement of osteopontin. Stimulation of crystal–cell adhesion impairs the opening of mitochondrial permeability transition pores (mPTP) in tubular cells and produces oxidative stress, apoptosis, and osteopontin expression. Macrophages phagocytose and digest a small amount of crystals, but many crystals aggregate into a mass containing osteopontin and epithelial cell debris and are excreted into the renal tubular lumen, becoming nuclei of urinary stones. This biomolecular mechanism is similar to atherosclerotic calcification. Based on these findings, new preventive treatments have been developed. Dietary control such as low-cholesterol intake and the ingestion of antioxidative foods and vegetables have successfully reduced the 5-year recurrence rate. Osteopontin antibodies and cyclosporine A, which blocks the opening of mPTP, have markedly inhibited the expression of osteopontin and urinary stone formation in animal models.

Keywords

Osteopontin Urinary stone Calcium oxalate Macrophage Atherosclerosis Mitochondria