Lieske John C, Regnier Cynthia, Dillon John J
Mayo Clinic Division of Nephrology and Hypertension and Mayo Hyperoxaluria Center, Rochester, Minnesota 55905, USA.
J Urol. 2008 Apr;179(4):1407-10. doi: 10.1016/j.juro.2007.11.062. Epub 2008 Mar 4.
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.
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).
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.
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.
我们检验了以下假设,即阳离子型磷酸盐结合剂盐酸司维拉姆可通过结合脂肪酸、结合磷酸盐并使钙游离以结合草酸盐和/或直接结合草酸盐,来降低肠道高草酸尿症患者的高草酸尿症和草酸钙过饱和度。次要目标是评估与肾结石相关的其他物质的尿排泄变化。
十名肠道高草酸尿症患者参加了一项非随机、开放标签的盐酸司维拉姆试验(每日3次,每次3200毫克,共7天)。
治疗后,平均尿草酸降低了17%(从每天0.84毫摩尔降至0.70毫摩尔),尿草酸与肌酐比值降低了11%(从0.055毫摩尔/毫摩尔降至0.049毫摩尔/毫摩尔,两者均无统计学显著性)。尿钙增加了25%(无统计学显著性)。尿柠檬酸盐降低了23%(p = 0.01),尿磷降低了44%(p = 0.0001)。草酸钙、磷酸二水钙、羟基磷灰石、尿酸和尿酸钠的平均过饱和度没有显著变化。然而,磷酸二水钙过饱和度的降低接近统计学显著性(p = 0.07)。基线时平均血清磷为3.6毫克/分升,治疗后为3.3毫克/分升(无统计学显著性)。没有患者发生低磷血症。一名患者因腹痛退出研究。
盐酸司维拉姆显著降低了尿磷排泄,对尿草酸的影响较小。由于对其他成分的抵消作用,包括尿钙增加和尿柠檬酸盐减少,草酸钙过饱和度没有降低。尽管盐酸司维拉姆可能不是纠正高草酸尿症的理想药物,但其降低磷酸钙过饱和度的潜力值得进一步研究。