Williams C P, Child D F, Hudson P R, Soysa L D, Davies G K, Davies M G, De Bolla A R
Department Medical Biochemistry, Maelor Hospital NHS Trust, Wrexham.
J Clin Pathol. 1996 Nov;49(11):881-8. doi: 10.1136/jcp.49.11.881.
To present experimental evidence in support of a proposed common cause for absorptive hypercalciuria, renal hypercalciuria, renal phosphate leak and enhancement of 1,25-(OH)2-vitamin D concentrations in patients presenting with renal stone disease; and to suggest further investigation with a view to new management.
An oral calcium loading test was administered to 15 patients with renal stones and 10 normal controls in the fasting state: urine and blood were collected hourly. After the second urine sample, 400 mg calcium dissolved in water was administered orally. Serum calcium, albumin, parathyroid hormone (PTH), and phosphate were measured together with urine calcium clearance and urinary phosphate from which the TmPO4/glomerular filtration rate (GFR) ratio was calculated. Serum 1,25-(OH)2-vitamin D was measured in the first serum sample. In addition, 24 hour urine calcium results were collected retrospectively from the patients' case notes over the previous 18 months.
In the basal state, renal stone patients had an overall greater phosphaturia (lower TmPO4/GFR: median 1.72 compared with 2.10 in controls) and increased calcium clearance. Serum corrected calcium and PTH concentrations did not differ between the groups. After calcium loading, serum calcium and urine calcium clearance rose in both groups, with patients with renal stones experiencing a greater percentage fall in phosphaturia. In both groups TmPO4/GFR fell (greater phosphaturia) with increased serum corrected calcium, with the patients showing notably greater phosphaturia for any given calcium concentration. Patients also had notably greater phosphaturia compared with the serum calcium concentration for any given PTH value. Serum 1,25-(OH)2-vitamin D was higher in patients than controls and for any 1,25-(OH)2-vitamin D concentration phosphaturia measured against serum calcium was greater in patients than controls. 1,25-(OH)2-vitamin D did not correlate with phosphaturia relative to serum calcium concentrations within the patient and control groups.
It is proposed that patients with idiopathic hypercalciuria have an "inappropriately' high phosphate excretion for any given serum calcium concentration. Loss of phosphate may induce increased activation of 1,25-(OH)2-vitamin D. Some of the commonly described causes of stone formation may be manifestations of a single mechanism.
提供实验证据，支持对患有肾结石疾病的患者中吸收性高钙尿症、肾性高钙尿症、肾磷酸盐泄漏以及1,25 -（OH）₂ - 维生素D浓度升高提出的共同病因；并建议进一步调查以期采用新的治疗方法。
对15例肾结石患者和10名正常对照者在空腹状态下进行口服钙负荷试验：每小时收集尿液和血液。在第二次尿液样本采集后，口服溶解于水中的400毫克钙。检测血清钙、白蛋白、甲状旁腺激素（PTH）和磷酸盐，同时计算尿钙清除率和尿磷酸盐，并据此计算TmPO₄/肾小球滤过率（GFR）比值。在首个血清样本中检测血清1,25 -（OH）₂ - 维生素D。此外，回顾性收集患者前18个月病历中的24小时尿钙结果。
在基础状态下，肾结石患者总体上磷酸盐尿更多（TmPO₄/GFR更低：中位数为1.72，而对照组为2.10）且钙清除率增加。两组间血清校正钙和PTH浓度无差异。钙负荷后，两组血清钙和尿钙清除率均升高，肾结石患者磷酸盐尿的下降百分比更大。两组中，随着血清校正钙升高，TmPO₄/GFR下降（磷酸盐尿增加），在任何给定钙浓度下，患者的磷酸盐尿明显更高。对于任何给定的PTH值，患者的磷酸盐尿与血清钙浓度相比也明显更高。患者血清1,25 -（OH）₂ - 维生素D高于对照组，对于任何1,25 -（OH）₂ - 维生素D浓度，患者相对于血清钙测量的磷酸盐尿高于对照组。在患者组和对照组中，1,25 -（OH）₂ - 维生素D与相对于血清钙浓度的磷酸盐尿无相关性。
提出特发性高钙尿症患者对于任何给定血清钙浓度都有“不适当”的高磷酸盐排泄。磷酸盐的丢失可能导致1,25 -（OH）₂ - 维生素D的活化增加。一些常见的结石形成原因可能是单一机制的表现。
