Separate Effects of Urinary Chondroitin Sulphate and Heparan Sulphate on the Crystallization of Urinary Calcium Oxalate: Differences between Stone Formers and Normal Control Subjects

1993 ◽  
Vol 85 (1) ◽  
pp. 33-39 ◽  
Author(s):  
D. K. Y. Shum ◽  
M. D. I. Gohel

1. Urinary glycosaminoglycans were recovered from the papain digest of polyanions precipitated sequentially by cetylpyridinium chloride and sodium acetate-saturated ethanol. Those from the early morning urine of 48 stone formers and 43 normal control subjects measured 11 and 16 μg of uronic acid/ml of urine, respectively. 2. Preparative agarose gel electrophoresis of the recovered glycosaminoglycans in barium acetate buffer (pH 5.8) yielded fractions containing purely chondroitin sulphate, co-polymeric chondroitin/dermatan sulphates and heparan sulphate. Identification was based on the susceptibility of the fractions to chondroitinase or nitrous acid treatment. Similar compositions of glycosaminoglycan classes were observed in samples from stone formers and normal control subjects. 3. The fractionated glycosaminoglycans were dissolved in urine ultrafiltrate to assay for nucleation-promoting and growth-inhibiting activities towards crystallization of urinary calcium oxalate. When compared at the same uronic acid concentration, both the urinary chondroitin sulphate isomers and heparan sulphates of stone formers demonstrated the capacity to enhance crystal nucleation from calcium oxalate endogenous in urine ultrafiltrates, whereas only urinary heparan sulphates of normal control subjects demonstrated this capacity. 4. Tissue-derived reference chondroitin sulphate, dermatan sulphate and heparin, when similarly tested, showed negligible crystal nucleation-promoting activity. The tissue-derived heparan sulphate was similar to the urinary heparan sulphates in showing marked crystal nucleation-promoting activity. 5. Crystal-growth inhibitory activity was evident in all urinary glycosaminoglycan fractions studied. In particular, urinary heparan sulphate of normal control subjects showed higher activity than that of stone formers or the chondroitin sulphate isomers of both stone formers and normal control subjects (P <0.005).

1990 ◽  
Vol 79 (2) ◽  
pp. 113-116 ◽  
Author(s):  
Bruno Baggio ◽  
Giovanni Marzaro ◽  
Giovanni Gambaro ◽  
Francesco Marchini ◽  
Hibbard E. Williams ◽  
...  

1. This study was performed to test the hypothesis that glycosaminoglycans may play an important role in the observed abnormalities in oxalate flux seen in patients with calcium oxalate nephrolithiasis. 2. Oxalate flux rate, erythrocyte membrane glycosaminoglycan content, membrane protein phosphorylation and effect of heparan sulphate on erythrocyte oxalate flux in vitro were studied in control subjects and patients with calcium oxalate nephrolithiasis. 3. In comparison with control subjects, renal stone-formers showed a significantly higher oxalate self-exchange, a lower erythrocyte membrane glycosaminoglycan content and a higher membrane phosphorylation rate. In stone-formers, erythrocyte glycosaminoglycan content correlated inversely with both oxalate flux rate and protein phosphorylation. In vitro, heparan sulphate promoted a significant fall in the rate of oxalate self-exchange. 4. These findings support the hypothesis that a lower erythrocyte membrane content of glycosaminoglycans enhances membrane protein phosphorylation, leading to an increased rate of transmembrane oxalate flux.


Author(s):  
L Bower ◽  
C Warren ◽  
G Manley

Quantitation of uronic acid precipitable by cetylpyridinium chloride (CPC) and electrophoretic separation of glycosaminoglycans were performed on sera from patients with chronic renal failure and compared to normal controls. Serum CPC-precipitable uronic acid (CpUA) levels in patients with renal failure were significantly higher (mean 13·7 mg/L, range 7·1–23·6 mg/L) than normal controls (mean 9·6 mg/L, range 5·1–13·9 mg/L) due to increased concentrations of low sulphated chondroitin sulphate. A positive correlation between serum CpUA and creatinine was found in renal failure patients. Urine CpUA excretion was raised in renal failure patients compared to normal controls with an increased excretion of chondroitin sulphate (Ch-S) of reduced electrophoretic mobility. Heparan sulphate (HS), a major glycosaminoglycan in normal urine, was absent from the urine of these patients. The possible origin of urine glycosaminoglycans and the role of the kidney in glycosaminoglycan metabolism are discussed.


1994 ◽  
Vol 5 (5) ◽  
pp. S46
Author(s):  
E M Worcester

Calcium stones occur because renal tubular fluid and urine are supersaturated with respect to calcium oxalate and phosphate. The process of stone formation includes crystal nucleation, growth, aggregation, and attachment to renal epithelia. Urine contains macromolecules that modify these processes and may protect against stone formation. Attention has focused especially on inhibitors of crystal growth, and several have been isolated from urine, including nephrocalcin, an acidic phosphorylated glycoprotein that contains several residues of gamma-carboxyglutamic acid per molecule; osteopontin (uropontin), a phosphorylated glycoprotein also found in bone matrix; uronic acid-rich protein, which contains a covalently bound glycosaminoglycan residue; and several others. Abnormalities in structure and/or function have been detected in some of these proteins in stone formers' urine. However, the overall ability of urinary macromolecules to inhibit calcium oxalate crystal growth is often normal in stone formers. Recently, attention has been focused on the ability of these molecules to inhibit other stages in stone formation. Nephrocalcin can inhibit crystal nucleation, for example, and both nephrocalcin and Tamm-Horsfall protein inhibit crystal aggregation. Nephrocalcin and Tamm-Horsfall protein from stone formers are less active in preventing aggregation, and under some conditions, Tamm-Horsfall protein may promote the formation of crystal aggregates, especially in the presence of high concentrations of calcium. The structural abnormalities responsible for impaired inhibitory activity are not completely understood.


2001 ◽  
Vol 85 (6) ◽  
pp. 616-620 ◽  
Author(s):  
H. Al Zahrani ◽  
R.W. Norman ◽  
C. Thompson ◽  
S. Weerasinghe

Author(s):  
Daniel G Fuster ◽  
Gaétan A Morard ◽  
Lisa Schneider ◽  
Cedric Mattmann ◽  
David Lüthi ◽  
...  

Abstract Background Sex-specific differences in nephrolithiasis with respect to both distribution of prevalence and stone composition are widely described and may be influenced by sex hormones. Methods We conducted a cross-sectional analysis of the relationship between 24-hour urinary sex hormone metabolites measured by gas chromatography–mass spectrometry with urinary calcium, oxalate and citrate excretion in a cohort of 628 kidney stone formers from a tertiary care hospital in Switzerland, taking demographic characteristics, kidney function and dietary factors into account. Results We observed a positive association of urinary calcium with urinary testosterone and 17β-estradiol. Positive associations of urinary calcium with dehydroepiandrosterone, 5α-DH-testosterone, etiocholanolone, androsterone, and estriol were modified by net gastrointestinal alkali absorption or urinary sulfate excretion. As the only sex hormone, dehydroepiandrosterone was inversely associated with urinary oxalate excretion in adjusted analyses. Urinary citrate correlated positively with urinary testosterone. Associations of urinary citrate with urinary androsterone, 17β-estradiol and estriol were modified by urinary sulfate or sodium, or by sex. Conclusions Urinary androgens and estrogens are significantly associated with urinary calcium and citrate excretion, and associations are in part modified by diet. Our data furthermore reveal dehydroepiandrosterone as a novel factor associated with urinary oxalate excretion in humans.


1969 ◽  
Vol 114 (1) ◽  
pp. 89-96 ◽  
Author(s):  
G. Manley ◽  
R. N. Mullinger ◽  
P. H. Lloyd

1. Glycosaminoglycans were liberated from old and young human ascending aortae by digestion with papain. Heparan sulphate and chondroitin sulphate were separated by the different solubilities of their complexes with cetylpyridinium chloride in solutions of sodium chloride. Final fractionation was achieved by salt-gradient column chromatography on Dowex 1 (Cl−form). 2. Heparan sulphate from old aortae showed a slight, but consistent, increase in sulphation compared with heparan sulphate from young aortae. 3. The major amino acids associated with aortic heparan sulphate and chondroitin sulphate were serine, glycine, glutamic acid and aspartic acid. Heparan sulphate and chondroitin sulphate from old aortae contained about twice as much total amino acid as heparan sulphate and chondroitin sulphate from young aortae. Alkali hydrolysis resulted in the destruction of more serine in chondroitin sulphate from old, compared with young, aortae. 4. Molecular weights of glycosaminoglycans from old and young aortae were found to be similar, and in the region of 35000. 5. It is suggested that there is an increased degree of protein–glycosaminoglycan cross-linking in old aortae.


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