Is idiopathic recurrent calcium urolithiasis in males a cellular disease? Laboratory findings in plasma, urine and erythrocytes, emphasizing the absence and presence of stones, oxidative and mineral metabolism: an observational study
Is idiopathic recurrent calcium urolithiasis in males a cellular disease? Laboratory findings in plasma, urine and erythrocytes, emphasizing the absence and presence of stones, oxidative and mineral metabolism: an observational study
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DOI：
10.1515/cclm.2005.103
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发表时间：
2005-01-01
影响因子：
6.8
通讯作者：
Schmiedl, A
中科院分区：
文献类型：
--
作者：
Schwille, PO;Manoharan, M;Schmiedl, A
背景：特发性复发性钙性尿石症（IRCU）是一种以草酸钙（CaOx）和/或磷酸钙(CaPi) -m-组成的结石为特征的疾病，其发病部位尚不确定，因为尿液中Ox、Ca和Pi紊乱等结石的危险因素并未定期观察到。目的：评估IRCU患者是否存在抗氧化剂和氧化剂失衡，随后出现尿液、血浆和细胞内矿物质平衡异常以及结石。方法：在标准化条件下，在实验室对男性进行调查，组织3次试验。试验1是横断面的，比较有（n = 111）和无原位结石（n = 126）的IRCU患者，重点关注尿和血浆中氧嘌呤和矿物质的异常，以及疾病的代谢活性（MA）。试验2采用部分对照（n= 14名健康受试者；n= 53名IRCU患者），比较血浆总抗氧化状态（TAS）和尿酸（人类主要抗氧化剂）水平，采用IRCU患者血浆中尿酸、抗坏血酸、白蛋白、x-生育酚和矿物质、尿矿物质、CaOx和CaPi（羟基磷灰石）过饱和度的低（n=26）和高（n=27） TAS亚群。试验3，包括无结石IRCU患者（n=8）和健康对照（n=8），比较了血浆和红细胞（红细胞）中的矿物质和矿物质比例。已确立的分析方法贯穿始终。结果：在试验1中，结石患者尿毒症、低黄嘌呤尿和蛋白尿升高，尿酸分数尿清除率（FE）降低，MA与尿毒症和尿总蛋白排泄呈正相关。在试验2中，与健康对照组相比，IRCU患者的TAS显著降低；TAS低与血浆尿酸、白蛋白低，抗坏血酸、x-生育酚和类旁腺激素不变，fe -尿酸和Pi排泄增加一致，后者与TAS呈负相关。在试验3中，与对照组相比，IRCU患者血浆矿物质显著减少，Ca/Pi、(Ca/Pi)/Mg和(Ca/Pi)/Na摩尔比增加；后一比值在红细胞中也升高，并与血浆中相同比值高度正相关。结论：在IRCU中，1)原位肾结石合并高空腹尿毒症、高低黄嘌呤尿和蛋白尿以及高MA提示结石形成的系统性代谢异常；2)经常出现抗氧化缺陷，与结石有无无关，但与肾尿酸循环不良、低尿酸血症和低白蛋白血症、尿Pi排泄过度和低MA明显相关；3)血浆TAS低，尿液、血浆和红细胞中Ca/Pi等矿物质比紊乱，但尿Ca盐过饱和不变，这与CaPi固体和Ca微石形成始于氧化损伤细胞的观点相一致。
Background: The site of origin of idiopathic recurrent calcium urolithiasis (IRCU) - a disorder characterized by stones composed of calcium oxalate (CaOx) and/ or calcium phosphate (CaPi) -m- is uncertain, because in urine such risk factors for stones as disturbed Ox, Ca and Pi are not regularly observed. Aims: To evaluate whether imbalance of antioxidants and oxidants might be present in IRCU patients that is then followed by abnormal urine, plasma and intracellular mineral homeostasis, and stones. Methods: Males were investigated in the laboratory under standardized conditions, and three trials were organized. Trial 1 was cross-sectional, comparing IRCU patients with (n 111) and without stones in situ (n = 126), focussing on abnormalities of oxypurines and minerals in urine and plasma, and metabolic activity (MA) of the disease. Trial 2 was partly controlled (n = 14 healthy subjects; n = 53 IRCU patients), comparing the plasma levels of total antioxidant status (TAS) and uric acid, the major antioxidant in humans, using the subsets Low (n=26) and High (n=27) TAS among IRCU patients in terms of plasma levels of uric acid, ascorbic acid, albumin, (x-tocopherol and minerals, urinary minerals, CaOx and CaPi (hydroxyapatite) supersaturation. Trial 3, comprising stone-free IRCU patients (n=8) and healthy controls (n=8), compared minerals and mineral ratios in plasma and red blood cells (RBCs). Established analytical methodologies were used throughout. Results: In trial 1, uricemia, hypoxanthinuria and proteinuria were elevated, fractional urinary clearance (FE) of uric acid was decreased in stone-bearing patients, and MA correlated positively with uricemia and urinary total protein excretion. In trial 2, TAS was significantly decreased in IRCU patients vs. healthy controls; low TAS coincided with low plasma uric acid and albumin, unchanged ascorbic acid, (x-tocopherol and parathy-roid hormone, but increased FE-uric acid and Pi excretion; the latter correlated negatively with TAS. In trial 3, plasma minerals were significantly decreased in IRCU patients vs. controls, and Ca/Pi, (Ca/Pi)/Mg and (Ca/Pi)/Na molar ratios increased; the latter ratio was also increased in RBCs, and correlated highly positively with the same ratio in plasma. Conclusions: In IRCU 1) renal stones in situ in combination with high fasting uricemia, high hypoxanthinuria and proteinuria, and high MA suggest that a systemic metabolic anomaly underlies stone formation; 2) antioxidant deficit is frequent, unrelated to the presence or absence of stones but apparently related to poor renal uric acid recycling, low uricemia and albuminemia, exaggerated urinary Pi excretion, and low MA; 3) the combination of low plasma TAS, disordered Ca/Pi and other mineral ratios in urine, plasma and RBCs, but unchanged urinary Ca salt supersaturation is compatible with the view that CaPi solid and Ca microlith formation start inside oxidatively damaged cells.