chondroitin-sulfates and Kidney-Calculi

Topics: Calcium Oxalate; Chondroitin Sulfates; Crystallization; Glycosaminoglycans; Heparin; Humans; Kidney Calculi; Urinary Calculi

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

The effect of glycosaminoglycans (GAGs) in urinary crystal inhibition has been shown in vitro, but their inhibitor role in vivo has not been precisely determined in stone-forming patients. The aim of this study was to compare the levels of total GAGs and their components in primary stone-forming patients and a healthy control group and to investigate the impact of shockwave lithotripsy (SWL).. Thirty-eight patients with primary kidney stones and 31 healthy controls were included in this prospective study. Total urinary GAG concentrations were determined by the dimethylene blue assay (DMB), and GAG fractions (chondroitin sulfate, heparan sulfate, and dermatan sulfate) were studied by cellulose acetate electrophoresis. Analysis was repeated after SWL in the stone patients.. Chondroitin sulfate was the major component secreted in the urine of the control subjects. Heparan sulfate was the major component in the urine of the stone patients with less chondroitin sulfate and dermatan sulfate (48%, 35%, 16.5%, respectively). Our study showed a significant increase in total urinary GAGs (4.75 v. 7.43 microg/mg of creatinine; P<0.0001) after SWL. Dermatan sulfate was the main component in this group (P<0.0001). The total urinary GAG concentrations remained high for at least 2 days after SWL.. The elevation in total GAGs after SWL indicates the presence of tissue injury, which also renders dermatan sulfate the principal excreted component. Studies with longer follow-up periods are needed to determine whether these changes in the excretion of GAG components persist.

Topics: Adult; Biomarkers; Chondroitin Sulfates; Creatinine; Dermatan Sulfate; Electrophoresis, Cellulose Acetate; Female; Heparitin Sulfate; Humans; Kidney Calculi; Lithotripsy; Male; Prognosis; Prospective Studies; Severity of Illness Index

Atomic force microscopy (AFM) was applied to the (-101) faces of calcium oxalate monohydrate (COM) crystals grown from calcium oxalate (CaOx) solutions. Microstructures of many spiral hillocks with step height of 1 nm were observed on the faces. Then using AFM in situ, we analysed the re-growth process of the spiral steps on the face of COM seed-crystals in CaOx growth solutions that contained growth inhibitors of glycosaminoglycans and studied their inhibition mechanisms on COM crystals. The total morphology of the faces of COM seed crystals re-grown in the CaOx growth solutions was assessed by scanning electron microscopy (SEM). In the growth solution without glycosaminoglycans (control experiment) or with chondroitin sulphate (ChS), AFM images and SEM micrographs of the faces of the re-grown seed crystals showed two-dimensional (2D) nucleation although 2D nucleation was delayed in the presence of ChS. However, the addition of dermatan sulphate (DS) to the growth solution resulted in isotropic growth by a step flow mode and spiral mechanism. With regard to the main inhibition mechanisms of two glycosaminoglycans (ChS and DS) on COM crystals, it can be concluded from these results that ChS delays 2D nucleation and DS inhibits 2D nucleation.

Topics: Calcium Oxalate; Chondroitin Sulfates; Crystallization; Dermatan Sulfate; Glycosaminoglycans; Humans; In Vitro Techniques; Kidney Calculi; Microscopy, Atomic Force; Microscopy, Electron, Scanning

In 50 calcium oxalate stone-forming patients, the total excretion of glycosaminoglycans (GAGs) and of four subgroups [chondroitin-4-sulfate (CS-A), chondroitin-6-sulfate (CS-C), dermatan sulfate (DS) and hyaluronic acid (HY)] were investigated before extracorporeal shock wave lithotripsy (ESWL) and during the subsequent 5 days. The standard value was determined by reference to a group of healthy test subjects. The excretion of GAGs was significantly higher in healthy test persons than in stone-forming patients. Twenty-four hours after ESWL administration, GAG excretion was enhanced significantly but returned to normal values over the course of 3 days. ESWL had no influence on the proportional composition of GAG subgroups CS-A, CS-C, DS and HY. The increase in GAG excretion after ESWL indicates a transient injury of renal tissue or of the mucus layer lining the urothelium. This lesion, however, can be regarded as temporary with later restitutio ad integrum.

Topics: Adult; Aged; Aged, 80 and over; Calcium Oxalate; Chondroitin; Chondroitin Sulfates; Creatinine; Dermatan Sulfate; Epithelium; Female; Glycosaminoglycans; Humans; Hyaluronic Acid; Kidney; Kidney Calculi; Lithotripsy; Male; Metabolic Clearance Rate; Middle Aged; Predictive Value of Tests; Sex Factors

The possibility that hypercalciuria could cause calcium stone formation through a mechanism other than by increasing urinary saturation of stone-forming calcium salts was explored. The effect of increasing calcium concentration on the inhibitor activity against the spontaneous precipitation of calcium oxalate was examined in whole urine (in the presence of naturally occurring inhibitors) and in synthetic media (with added inhibitors). In 11 patients with calcium nephrolithiasis, the induced hypercalciuria from calcium supplementation (600 mg/day) caused a significant fall in the urinary inhibitory activity against calcium oxalate precipitation, as shown by a decline in the formation product ratio from 12.6 +/- 1.1 SEM to 9.6 +/- 1.4 (P less than 0.005). In order to more fully explore this observation, the effect of increasing calcium concentration on the inhibitory activities of citrate (2 mM), chondroitin sulfate (0.05 mg/liter) and a heterogeneous group of naturally-occurring urinary inhibitors (1.0 mg/liter) against calcium oxalate precipitation was examined in vitro in synthetic solutions. The inhibitory actions of both citrate and chondroitin sulfate were significantly attenuated by increasing calcium concentration from 0.25 mM to 6.0 mM (P less than 0.01). However, raising the calcium concentration in synthetic media containing a mixture of partially purified urinary inhibitors produced a significant rise in the urinary inhibitory activity of this macromolecular mixture (P less than 0.01). We conclude that hypercalciuria can attenuate the inhibitory activities of citrate and chondroitin sulfate against calcium oxalate precipitation while at the same time accentuating the inhibitory activity of naturally-occurring urinary inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Calcium; Calcium Oxalate; Calcium, Dietary; Chondroitin Sulfates; Citrates; Citric Acid; Crystallization; Humans; In Vitro Techniques; Kidney Calculi

A method was developed for the determination of urinary chondroitin sulphate (CS), including dermatan sulphate and chondroitin 4 and 6-sulphates, using an enzymatic degradation with chondroitinase-ABC followed by precipitation with Alcian blue, whereby CS was determined as the difference between undigested and chondroitinase digested material. The method was linear in the range 0-100 mg l-1 with a detection limit of 1 mg l-1 and allowed determinations on small urine volumes without pretreatment of the urine. It could be demonstrated that males excreted more CS than females, and growing children had the highest urinary content of CS. Renal calcium stone formers did not differ from healthy controls in urinary CS. Patients with acromegaly had a higher excretion of CS compared with controls. There was also, in these patients, a positive correlation between the serum growth hormone levels and the urinary CS, indicating that CS-excretion may be an estimate of the activity of the pituitary disorder.

Topics: Acromegaly; Alcian Blue; Chemical Precipitation; Chondroitin; Chondroitin Sulfates; Dermatan Sulfate; Female; Heparin; Humans; Kidney Calculi; Male; Pentosan Sulfuric Polyester