Use of sevelamer hydrochloride as an oxalate binder.

PURPOSE: We tested the hypothesis that the cationic phosphate binder sevelamer hydrochloride could reduce hyperoxaluria and calcium oxalate supersaturation in patients with enteric hyperoxaluria by binding fatty acids, binding phosphate and rendering calcium free to bind oxalate, and/or directly binding oxalate. A secondary objective was to assess changes in the urinary excretion of other substances associated with nephrolithiasis. MATERIALS AND METHODS: Ten patients with enteric hyperoxaluria were enrolled in a nonrandomized, open label trial of sevelamer hydrochloride (3,200 mg 3 times daily for 7 days). RESULTS: With treatment mean urinary oxalate decreased 17% (0.84 to 0.70 mmol per day) and the urinary oxalate-to-creatinine ratio decreased 11% (0.055 to 0.049 mmol/mmol, p not significant for both). Urinary calcium increased 25% (p not significant). Urinary citrate decreased 23% (p = 0.01) and urinary phosphorus decreased 44% (p = 0.0001). Mean supersaturation of calcium oxalate, brushite, hydroxyapatite, uric acid and sodium urate did not change significantly. However, the decrease in brushite supersaturation approached statistical significance (p = 0.07). Mean serum phosphorus was 3.6 mg/dl at baseline and 3.3 mg/dl with therapy (p not significant). Hypophosphatemia did not develop in any patients. One patient dropped out of study due to abdominal pain. CONCLUSIONS: Sevelamer hydrochloride dramatically decreased urinary phosphorus excretion with a lesser effect on urinary oxalate. Supersaturation of calcium oxalate did not decrease due to countervailing effects on other constituents including an increase in urinary calcium and a decrease in urinary citrate. Although sevelamer hydrochloride may not be an ideal agent for correcting hyperoxaluria, its potential to reduce calcium phosphate supersaturation merits further investigation.

Detectable clonal mosaicism from birth to old age and its relationship to cancer.

We detected clonal mosaicism for large chromosomal anomalies (duplications, deletions and uniparental disomy) using SNP microarray data from over 50,000 subjects recruited for genome-wide association studies. This detection method requires a relatively high frequency of cells with the same abnormal karyotype (>5-10%; presumably of clonal origin) in the presence of normal cells. The frequency of detectable clonal mosaicism in peripheral blood is low (<0.5%) from birth until 50 years of age, after which it rapidly rises to 2-3% in the elderly. Many of the mosaic anomalies are characteristic of those found in hematological cancers and identify common deleted regions with genes previously associated with these cancers. Although only 3% of subjects with detectable clonal mosaicism had any record of hematological cancer before DNA sampling, those without a previous diagnosis have an estimated tenfold higher risk of a subsequent hematological cancer (95% confidence interval = 6-18).

Use of a probiotic to decrease enteric hyperoxaluria.

BACKGROUND: Patients with inflammatory bowel disease have a 10- to 100-fold increased risk of nephrolithiasis, with enteric hyperoxaluria being the major risk factor for these and other patients with fat malabsorptive states. Endogenous components of the intestinal microflora can potentially limit dietary oxalate absorption. METHODS: Ten patients were studied with chronic fat malabsorption, calcium oxalate stones, and hyperoxaluria thought to be caused by jejunoileal bypass (1) and Roux-en-Y gastric bypass surgery for obesity (4), dumping syndrome secondary to gastrectomy (2), celiac sprue (1), chronic pancreatitis (1), and ulcerative colitis in remission (1). For 3 months, patients received increasing doses of a lactic acid bacteria mixture (Oxadrop), VSL Pharmaceuticals), followed by a washout month. Twenty-four-hour urine collections were performed at baseline and after each month. RESULTS: Mean urinary oxalate excretion fell by 19% after 1 month (1 dose per day, P < 0.05), and oxalate excretion remained reduced by 24% during the second month (2 doses per day, P < 0.05). During the third month on 3 doses per day oxalate excretion increased slightly, so that the mean was close to the baseline established off treatment. Urinary oxalate again fell 20% from baseline during the washout period. Calcium oxalate supersaturation was reduced while on Oxadrop, largely due to the decrease in oxalate excretion, although mean changes did not reach statistical significance. CONCLUSION: Manipulation of gastrointestinal (GI) flora can influence urinary oxalate excretion to reduce urinary supersaturation levels. These changes could have a salutary effect on stone formation rates. Further studies will be needed to establish the optimal dosing regimen.