Pak C Y, Oata M, Lawrence E C, Snyder W
J Clin Invest. 1974 Aug;54(2):387-400. doi: 10.1172/JCI107774.
The causes for the hypercalciuria and diagnostic criteria for the various forms of hypercalciuria were sought in 56 patients with hypercalcemia or nephrolithiasis (Ca stones), by a careful assessment of parathyroid function and calcium metabolism. A study protocol for the evaluation of hypercalciuria, based on a constant liquid synthetic diet, was developed. In 26 cases of primary hyperparathyroidism, characteristic features were: hypercalcemia, high urinary cyclic AMP (cAMP, 8.58+/-3.63 SD mumol/g creatinine; normal, 4.02+/-0.70 mumol/g creatinine), high immunoreactive serum parathyroid hormone (PTH), hypercalciuria, the urinary Ca exceeding absorbed Ca from intestinal tract (Ca(A)), high fasting urinary Ca (0.2 mg/mg creatinine or greater), and low bone density by (125)I photon absorption. The results suggest that hypercalciuria is partly secondary to an excessive skeletal resorption (resorptive hypercalciuria). The 22 cases with renal stones had normocalcemia, hypercalciuria, intestinal hyperabsorption of calcium, normal or low serum PTH and urinary cAMP, normal fasting urinary Ca, and normal bone density. Since their Ca(A) exceeded urinary Ca, the hypercalciuria probably resulted from an intestinal hyperabsorption of Ca (absorptive hypercalciuria). The primacy of intestinal Ca hyperabsorption was confirmed by responses to Ca load and deprivation under a metabolic dietary regimen. During a Ca load of 1,700 mg/day, there was an exaggerated increase in the renal excretion of Ca and a suppression of cAMP excretion. The urinary Ca of 453+/-154 SD mg/day was significantly higher than the control group's 211+/-42 mg/day. The urinary cAMP of 2.26+/-0.56 mumol/g creatinine was significantly lower than in the control group. In contrast, when the intestinal absorption of calcium was limited by cellulose phosphate, the hypercalciuria was corrected and the suppressed renal excretion of cAMP returned towards normal. Two cases with renal stones had normocalcemia, hypercalciuria, and high urinary cAMP or serum PTH. Since Ca(A) was less than urinary Ca, the hypercalciuria may have been secondary to an impaired renal tubular reabsorption of Ca (renal hypercalciuria). Six cases with renal stones had normal values of serum Ca, urinary Ca, urinary cAMP, and serum PTH (normocalciuric nephrolithiasis). Their Ca(A) exceeded urinary Ca, and fasting urinary Ca and bone density were normal. The results support the proposed mechanisms for the hypercalciuria and provide reliable diagnostic criteria for the various forms of hypercalciuria.
通过仔细评估甲状旁腺功能和钙代谢，在56例高钙血症或肾结石（钙结石）患者中探寻高钙尿症的病因及各种形式高钙尿症的诊断标准。制定了一项基于恒定液体合成饮食的高钙尿症评估研究方案。在26例原发性甲状旁腺功能亢进病例中，特征性表现为：高钙血症、高尿环磷腺苷（cAMP，8.58±3.63标准差μmol/g肌酐；正常，4.02±0.70μmol/g肌酐）、高免疫反应性血清甲状旁腺激素（PTH）、高钙尿症、尿钙超过肠道吸收钙（Ca(A)）、高空腹尿钙（0.2mg/mg肌酐或更高）以及通过（125）I光子吸收测定的低骨密度。结果表明，高钙尿症部分继发于过度的骨骼吸收（吸收性高钙尿症）。22例肾结石患者血钙正常、高钙尿症、肠道钙吸收增加、血清PTH和尿cAMP正常或降低、空腹尿钙正常以及骨密度正常。由于他们的Ca(A)超过尿钙，高钙尿症可能是由肠道钙吸收增加所致（吸收性高钙尿症）。在代谢饮食方案下对钙负荷和钙缺乏的反应证实了肠道钙吸收增加的首要地位。在每日1700mg钙负荷期间，尿钙排泄显著增加，cAMP排泄受到抑制。453±154标准差mg/天的尿钙显著高于对照组的211±42mg/天。2.26±0.56μmol/g肌酐的尿cAMP显著低于对照组。相反，当用磷酸纤维素限制肠道钙吸收时，高钙尿症得到纠正，受抑制的尿cAMP排泄恢复正常。2例肾结石患者血钙正常、高钙尿症、高尿cAMP或血清PTH升高。由于Ca(A)低于尿钙，高钙尿症可能继发于肾小管对钙的重吸收受损（肾性高钙尿症）。6例肾结石患者血清钙、尿钙、尿cAMP和血清PTH值正常（正常钙尿性肾结石）。他们的Ca(A)超过尿钙，空腹尿钙和骨密度正常。这些结果支持了所提出的高钙尿症机制，并为各种形式的高钙尿症提供了可靠的诊断标准。
