Urinary sulfated glycosaminoglycan insufficiency and chondroitin sulfate supplement in 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.

Urinary stone risk factors in the descendants of patients with kidney stone disease.

BACKGROUND: Evidence has indicated that immediate family members of nephrolithiasis patients had high opportunity to develop stones. However, they are usually not regarded to be at risk, since it is unclear if there are any lithogenic abnormalities found in non-stone-forming nephrolithiasis relatives. Our aim was to investigate urinary metabolic abnormalities in the children of nephrolithiasis patients, compared with the general population. METHODS: The 24-h urinary metabolic profile was studied for 28 calcium oxalate nephrolithiasis patients (NL) and 46 of their descendants (ND), as well as 40 non-stone-forming volunteers (V) and 34 of their descendants (VD). RESULTS: There was no difference between age, gender, and serum creatinine between NL vs. V (parental groups) and ND vs. VD (descendant groups). High urinary oxalate in nephrolithiasis and urinary calcium in their descendants was detected. In addition, an elevated urinary excretion rate of calcium, phosphate, protein, and albumin, along with low citrate excretion and high urinary supersaturation was observed in both the nephrolithiasis patients and their descendants. Approximate 17.8-24.4% of the nephrolithiasis descendants had a urinary supersaturation higher than the nephrolithiasis level, but none was found in VD group. The level of urinary supersaturation index was correlated with urinary protein and albumin excretion in nephrolithiasis family. CONCLUSION: It was demonstrated that nephrolithiasis offspring carried several urinary metabolic risks predisposing to stone formation which are similar to their parents, and about one in every five nephrolithiasis children had nephrolithiasis level urinary supersaturation.

LINE-1 hypomethylation induced by reactive oxygen species is mediated via depletion of S-adenosylmethionine.

Whether long interspersed nuclear element-1 (LINE-1) hypomethylation induced by reactive oxygen species (ROS) was mediated through the depletion of S-adenosylmethionine (SAM) was investigated. Bladder cancer (UM-UC-3 and TCCSUP) and human kidney (HK-2) cell lines were exposed to 20 µM H2O2 for 72 h to induce oxidative stress. Level of LINE-1 methylation, SAM and homocysteine (Hcy) was measured in the H2O2 -exposed cells. Effects of α-tocopheryl acetate (TA), N-acetylcysteine (NAC), methionine, SAM and folic acid on oxidative stress and LINE-1 methylation in the H2O2 -treated cells were explored. Viabilities of cells treated with H2O2 were not significantly changed. Intracellular ROS production and protein carbonyl content were significantly increased, but LINE-1 methylation was significantly decreased in the H2O2 -treated cells. LINE-1 methylation was restored by TA, NAC, methionine, SAM and folic acid. SAM level in H2O2 -treated cells was significantly decreased, while total glutathione was significantly increased. SAM level in H2O2 -treated cells was restored by NAC, methionine, SAM and folic acid; while, total glutathione level was normalized by TA and NAC. Hcy was significantly decreased in the H2O2 -treated cells and subsequently restored by NAC. In conclusion, in bladder cancer and normal kidney cells exposed to H2O2 , SAM and Hcy were decreased, but total glutathione was increased. Treatments with antioxidants (TA and NAC) and one-carbon metabolites (SAM, methionine and folic acid) restored these changes. This pioneer finding suggests that exposure of cells to ROS activates glutathione synthesis via the transsulfuration pathway leading to deficiency of Hcy, which consequently causes SAM depletion and eventual hypomethylation of LINE-1.