Strong inhibition of crystal–cell attachment by pediatric urinary macromolecules: a close relationship with high urinary citrate secretion

Miyake, Osamu; Kakimoto, Ken‐ichi; Tsujihata, Masao; Yoshimura, Kazuhiro; Takahara, Shiro; Okuyama, Äkïhïko

doi:10.1016/s0090-4295(01)01257-2

Cited by 19 publications

(11 citation statements)

References 7 publications

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“…The anti-lithogenic property of CS depends on the structure and sulfate groups. Some scientists also claimed that CS in children may contain higher anti-stone potency than CS found in adults [8, 22]. Regarding low urinary CS observed in children of urolithiasis, we believed that this might be one of the risks related to high probability of stone development in urolithiasis familial members.…”

Section: Resultsmentioning

confidence: 84%

Urinary sulfated glycosaminoglycan insufficiency and chondroitin sulfate supplement in urolithiasis

et al. 2019

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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.

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Section: Resultsmentioning

confidence: 84%

Urinary sulfated glycosaminoglycan insufficiency and chondroitin sulfate supplement in urolithiasis

et al. 2019

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“…Most of them provide some inhibitory effects in various process of stone formation. We have demonstrated that lower incidence of CaOX lithiasis in children may be attributed to stronger inhibition of CaOX crystal aggregation and crystal‐cell adhesion by the higher level of citrates or pediatric UMM, which might be affected by a higher concentration of GAG in children's urine 8,24 . Recently we reported that fibronectin was a potent stone inhibitor and that normal subjects showed a significantly higher concentration of fibronectin in UMM than stone formers 9,10 .…”

Section: Discussionmentioning

confidence: 96%

“…We have demonstrated that lower incidence of CaOX lithiasis in children may be attributed to stronger inhibition of CaOX crystal aggregation and crystal-cell adhesion by the higher level of citrates or pediatric UMM, which might be affected by a higher concentration of GAG in children's urine. 8,24 Recently we reported that fibronectin was a potent stone inhibitor and that normal subjects showed a significantly higher concentration of fibronectin in UMM than stone formers. 9,10 In the present study, we focused on whether or not UMM have a similar protective effect on oxalate-related renal epithelial cell injury, and compared this activity between normal subjects and stone former subjects.…”

Section: Discussionmentioning

confidence: 99%

“…Ebisuno et al reported that pretreatment with GAG significantly reduced the adherence of CaOX monohydrate crystals to MDCK cells, 25 and Miyake et al showed that pediatric UMM more potently inhibit the adhesion of calcium oxalate crystals to renal tubular cells than male adults. 24 Second, UMM may decrease an activation of free radical and lipid peroxidation including inflammatory response. Nevertheless, further studies will be needed to determine this result.…”

Section: Discussionmentioning

confidence: 99%

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Urinary macromolecules and renal tubular cell protection from oxalate injury: Comparison of normal subjects and recurrent stone formers

et al. 2006

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Aim:To determine whether urinary macromolecules (UMM), which are the high molecular weight substances in urine, can provide protection against the oxalate-associated injury to the renal tubular cells. Methods: UMM were extracted from 24-h urine of 12 healthy adult male volunteers and 13 recurrent-stone-former male patients. Urine parameters in relation to urolithiasis were measured, including the level of glycosaminoglycans (GAG) in the UMM. MadinDarby canine kidney (MDCK) cells were used to evaluate the protective activity of UMM from oxalate-induced cytotoxicity by LDH release measurement and methyl-thiazolyl tertrazolium (MTT) assay. Results: Considering urinary parameters, citrate was significantly higher in urine from normal subjects than stone-former subjects; the other parameters show no differences between the groups. Total UMM and the level of GAG in the UMM were also significantly higher in the normal subject group. Compared with normal subject and stone-former subject UMM, after cells were treated with the UMM and then exposed to oxalate solution, LDH release was significantly higher in stone-former group. In the MTT assay, we found that more viable cells were observed after treatment with UMM compared to control in both groups. Moreover, UMM from the normal subjects showed higher protective activity against oxalate-related cytotoxicity than UMM from the stone-former subjects. Conclusion: UMM protected renal epithelial cells from oxalate-related injury. This protective activity was found to be higher in normal subject UMM than stone-former UMM. Among other factors, a higher concentration of GAG and citrate in normal subject UMM might affect some parts in this finding.

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“…Due to the strong affinity between Ca and Ox and the low calcium oxalate (CaOx) solubility product, hypercalciuria and hyperoxaluria are the most common cause of renal stones. The excretion of urinary citrate (Cit), which forms a soluble compound with Ca, reduces CaOx formation by depreciating the available Ca ions to interact with Ox [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ]. Glycosaminoglycans (GAGs) (chondroitin sulfate, heparan sulfate, hyaluronic acid, dermatan sulfate, keratan sulfate) can also inhibit CaOx crystallization (this ability is attributed to at least the first three above) [ 1 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Age-Specific Excretion of Calcium, Oxalate, Citrate, and Glycosaminoglycans and Their Ratios in Healthy Children and Children with Urolithiasis

et al. 2021

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We analyzed children with urolithiasis with age- and gender-matched healthy children. Calcium (mmol/mmol creatinine) and the calcium/citrate ratio (mol/mmol) are the only variables that differentiate children before puberty from healthy children (ROC analysis confirmed only calcium/citrate as a significant variable with cut-off value > 0.84). Peri-pubertal children are distinguished from age- and gender-matched healthy children by the following variables: citrate (mmol/mol creatinine), calcium/citrate (mol/mmol), oxalate/glycosaminoglycans (mmol/g), oxalate/citrate ratios (mmol/mmol) and oxalate/(citrate × glycosaminoglycans) (mol oxalate × mol creatinine)/(mol citrate × g glycosaminoglycans). All variables were confirmed by ROC analysis with cut-off values ≤ 327.87, >1.02, >11.24, >0.12 and >0.03, respectively. These results indicate a different risk of urinary stones development before puberty vs. pubertal/postpubertal children and increasing importance (deficiency) of citrate and glycosaminoglycans in such children. J48 classifier confirmed the importance of the oxalate/(citrate × glycosaminoglycans) and the calcium/citrate ratios (Ox/Cit × GAG 0.22 and Cit/GAG 0.612) with the practically applicable classification tree for distinguishing between pubertal/postpubertal children with urolithiasis with age- and gender-matched healthy children.

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Strong inhibition of crystal–cell attachment by pediatric urinary macromolecules: a close relationship with high urinary citrate secretion

Cited by 19 publications

References 7 publications

Urinary sulfated glycosaminoglycan insufficiency and chondroitin sulfate supplement in urolithiasis

Urinary sulfated glycosaminoglycan insufficiency and chondroitin sulfate supplement in urolithiasis

Urinary macromolecules and renal tubular cell protection from oxalate injury: Comparison of normal subjects and recurrent stone formers

Age-Specific Excretion of Calcium, Oxalate, Citrate, and Glycosaminoglycans and Their Ratios in Healthy Children and Children with Urolithiasis

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