The purpose of this study is to confirm the hypocalciuric effect of rice bran experimentally and clinically. Urinary calcium excretion and its absorption in the intestine were reduced significantly by rice bran or phytin in rats fed high calcium diets, while there were no significant decreases with a low calcium diet. For the clinical study 70 patients with idiopathic hypercalciuria were treated with rice bran (10 gm. twice daily) for 1 month to 3 years. In almost all patients rice bran caused a significant decrease in urinary calcium excretion, which was maintained during treatment. Evidence of stones has decreased clearly among patients treated with rice bran for 1 to 3 years, although this might be a halfway judgment of the long-term treatment. We suggest that phytin should be the most effective substance to reduce the intestinal absorption of calcium and that rice bran treatment should be effective for prevention of recurrent urinary stone disease.

No abstract

The present investigation was designed to study the biological responses in cultures of Madin-Darby canine kidney (MDCK) cells exposed to calcium oxalate monohydrate (COM) crystals, the most common type of urinary crystals. The addition of COM crystals significantly accelerated the multiplication of MDCK cells and significantly activated the cell viability. After exposure of MDCK cells to COM crystals, scanning electron microscopy revealed that some crystals adhered to the plasma membrane and others were endocytosed by the cell. This cellular uptake of crystals was time dependent from 1 to 8 h and showed a specificity according to crystal type. However, the endocytosis of aggregated COM crystals was less marked than that of non-aggregated crystals. Pre-treatment with each of the glycosaminoglycans (sodium pentosan polysulphate, heparin, and chondroitin sulphate C) produced a significant reduction of the cellular uptake of COM crystals, suggesting that these glycosaminoglycans may play some critical roles in preventing the cellular uptake of crystals. Although investigation in further detail is necessary, we speculate that these crystal-cell interactions, that is, the cellular uptake of crystals and cell proliferation, may be among the earliest processes in the formation of kidney stones.

Adhesion and/or endocytosis of calcium oxalate crystals to the three kinds of tubular cells (Madin-Darby canine kidney (MDCK) cells, rat and human kidney) were demonstrated morphologically to presume the initial formation of kidney stone. After removal of the nonadhesion crystals, the cells were subsequently recultured in the vertical position. At various times thereafter, the interactions between COM crystals and MDCK cells were evaluated morphologically by SEM. COM crystals adhered to the surface of MDCK cells immediately, and the crystals were then endocytosed. The microvilli of the cells appeared to play an important role in these processes. At later times, some complexes that consist of aggregated calcium oxalate crystals and cell debris were observed sporadically. Kidney tissues were obtained from male Sprague-Dawley rats which were injected with sodium oxalate intraperitoneally. Experimentally induced calcium oxalate crystals were evaluated histologically using polarized light microscopy. Some crystals in the cortical portion were attached to the tubular epithelium or internalized into the luminal membrane. Whereas in the papilla, the aggregated crystals were observed lying free from the degenerated tubular lumen along with the cell debris. Human kidney tissues were obtained from 38 patients with calcium oxalate nephrolithiasis who underwent nephrolithotomy or partial nephrectomy before the era of ESWL. The specimens were examined for calcium crystals within the tubular lumen, attached to the tubular walls or internalized into the tubular cells, by polarized light microscopy. Approximately 50% of the specimens observed crystals attached to the tubular cell epithelium and some of them were seen inside the tubular cells. In conclusion, crystal-cell interaction resulted in movement of crystals from the lumen into the cells by an action of microvilli from the results of MDCK cells. However, it was not clear from the results in rats or human kidney tissue that crystal adhesion and/or endocytosis might be vital in the crystal growth in the kidney.

Although oxalate is a major component of kidney stones, the factors affecting renal oxalate handling are poorly understood. This uncertainty stems in part from complexities inherent to available preparations; thus the present studies examined oxalate handling in a simpler model system, LLC-PK1 cells, an epithelial cell line of porcine origin. Initial studies on monolayers in dishes demonstrated that these cells accumulate oxalate via a process or processes sensitive to the anion transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). Subsequent studies using LLC-PK1 monolayers on membrane filters examined the characteristics and distribution of these transporter(s). At the apical surface, DIDS-sensitive uptake was sensitive to [Cl-] but not [SO4(2-)] or [HCO3-] and was unaffected by alterations in pH or membrane potential. At the basolateral surface, oxalate uptake was [Cl-] insensitive but markedly affected by variation in pH, [SO4(2-)], or [HCO3-]. Uptake at the two membrane surfaces was also differentially affected by transport inhibitors and organic acids. Thus LLC-PK1 cells appear to express unique transporters at each membrane surface: oxalate/Cl- exchange at the apical surface and oxalate/SO4(2-) (or HCO3-) exchange at the basolateral surface.