heparitin-sulfate and Urolithiasis

Familial members of urolithiasis have high risk for stone development. We observed the low sulfated glycosaminoglycan (GAG) excretion in urolithiasis patients and their descendants. In this study, we investigated urinary excretion of sulfated GAG, chondroitin sulfate (CS), heparan sulfate (HS) and hyaluronic acid (HA) in urolithiasis and their children, and explored the effect of CS and HA supplement in urolithic hyperoxaluric rats. The 24-hour urines were collected from urolithiasis patients (28) and their children (40), as well as healthy controls (45) and their children (33) to measure urinary sulfated GAG, CS, HS and HA excretion rate. Our result showed that urinary sulfated GAG and CS were diminished in both urolithiasis patients and their children, while decreased HS and increased HA were observed only in urolithiasis patients. Percentage of HS per sulfated GAG increased in both urolithiasis patients and their children. In hyperoxaluric rats induced by ethylene glycol and vitamin D, we found that CS supplement could prevent stone formation, while HA supplement had no effect on stone formation. Our study revealed that decreased urinary GAG and CS excretion are common in familial members of urolithiasis patients, and CS supplement might be beneficial in calcium oxalate urolithiasis prophylaxis for hyperoxaluric patients.

Topics: Adult; Animals; Child; Chondroitin Sulfates; Creatinine; Dietary Supplements; Disease Models, Animal; Female; Glycosaminoglycans; Heparitin Sulfate; Humans; Hyaluronic Acid; Kidney; Male; Middle Aged; Rats; Rats, Wistar; Urolithiasis

Urinary polyanions recovered from the urine samples of kidney stone-formers and normal controls were subjected to preparative agarose gel electrophoresis, which yielded fractions 1-5 in a decreasing order of mobility. In both groups, chondroitin sulfates were identified in the fast-moving fractions and heparan sulfates in the slow-moving fractions. Furthermore, two types of heparan sulfates were identified based on their electrophoretic mobility: slow-moving and fast-moving. The fractionated urinary polyanions were then tested in an in vitro calcium oxalate crystallization assay and compared at the same uronic acid concentration, whereby, the chondroitin sulfates of stone-formers and heparan sulfates of normals enhanced crystal nucleation. Fraction 5 of the normals, containing glycoproteins (14-97 kDa) and associated glycosaminoglycans, were found to effectively inhibit crystallization. Papainization of this fraction in stone-formers revealed crystal-suppressive effects of glycoproteins, which was not seen in similar fractions of normals. It was concluded that glycoproteins could modulate the crystal-enhancing glycosaminoglycans such as chondroitin sulfates of stone-formers but not in normals. The differing crystallization activities of electrophoretic fraction 1 of normals and stone-formers revealed the presence of another class of glycosaminoglycan-hyaluronan. Hence, in the natural milieu, different macromolecules combine to have an overall outcome in the crystallization of calcium oxalate.

Topics: Adult; Calcium Oxalate; Chondroitin Sulfates; Crystallization; Electrophoresis, Agar Gel; Electrophoresis, Cellulose Acetate; Glycoproteins; Heparitin Sulfate; Humans; Kidney Calculi; Middle Aged; Urinary Calculi; Urolithiasis

To evaluate the interaction in the renal tubules between calcium oxalate microliths and glycosaminoglycans, especially heparan sulfate, we planned an experimentally-induced calcium oxalate microlith-producing model in rats. We found by immunofluorescence study and immunoelectron microscopy using the heparan sulfate antibody that heparan sulfate was produced in the renal tubular cells in the formation of calcium oxalate microliths and that heparan sulfate exists in the microliths. Heparan sulfate/crystal interaction might play a role as a nucleating agent and promote stone enlargement.

Topics: Animals; Calcium Oxalate; Crystallization; Disease Models, Animal; Fluorescent Antibody Technique; Heparitin Sulfate; Kidney Tubules; Male; Microscopy, Electron, Transmission; Microscopy, Immunoelectron; Rats; Rats, Wistar; Urolithiasis