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01-12-2012 | Invited Review

Biomolecular mechanism of urinary stone formation involving osteopontin

Authors: Kenjiro Kohri, Takahiro Yasui, Atsushi Okada, Masahito Hirose, Shuzo Hamamoto, Yasuhiro Fujii, Kazuhiro Niimi, Kazumi Taguchi

Published in: Urolithiasis | Issue 6/2012

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.

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Title: Biomolecular mechanism of urinary stone formation involving osteopontin
Authors: Kenjiro Kohri
Takahiro Yasui
Atsushi Okada
Masahito Hirose
Shuzo Hamamoto
Yasuhiro Fujii
Kazuhiro Niimi
Kazumi Taguchi
Publication date: 01-12-2012
Publisher: Springer-Verlag
Published in: Urolithiasis / Issue 6/2012
Print ISSN: 2194-7228
Electronic ISSN: 2194-7236
DOI: https://doi.org/10.1007/s00240-012-0514-y

At a glance: The STEP trials

Springer Medicine

Biomolecular mechanism of urinary stone formation involving osteopontin

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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