Schwille Paul Otto, Manoharan Mahimaidos, Schmiedl Angelika
Mineral Metabolism and Endocrine Research Laboratory, Department of Surgery, University of Erlangen-Nürnberg, Germany.
Clin Chem Lab Med. 2005;43(6):590-600. doi: 10.1515/CCLM.2005.103.
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)--is uncertain, because in urine such risk factors for stones as disturbed Ox, Ca and Pi are not regularly observed.
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.
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, alpha-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.
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, alpha-tocopherol and parathyroid 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.
In IRCU 1) renal stones in situ in combination with high fasting uricemia, high hypoxanthinuria and protein-uria, 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.
特发性复发性钙尿路结石（IRCU）——一种以草酸钙（CaOx）和/或磷酸钙（CaPi）结石为特征的疾病——的起源部位尚不确定，因为在尿液中，诸如草酸、钙和磷紊乱等结石风险因素并非经常出现。
评估IRCU患者体内抗氧化剂和氧化剂是否失衡，进而导致尿液、血浆和细胞内矿物质稳态异常以及结石形成。
在标准化条件下对男性进行实验室研究，并组织了三项试验。试验1为横断面研究，比较有原位结石（n = 111）和无原位结石（n = 126）的IRCU患者，重点关注尿液和血浆中氧嘌呤和矿物质的异常以及该疾病的代谢活性（MA）。试验2为部分对照试验（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，根据尿酸、抗坏血酸、白蛋白、α-生育酚和矿物质的血浆水平、尿矿物质、CaOx和CaPi（羟基磷灰石）过饱和度，将IRCU患者分为低TAS组（n = 26）和高TAS组（n = 27）。试验3包括无结石的IRCU患者（n = 8）和健康对照（n = 8），比较血浆和红细胞（RBC）中的矿物质及矿物质比率。全程采用既定的分析方法。
在试验1中，结石患者的血尿酸、次黄嘌呤尿症和蛋白尿升高，尿酸的尿分数清除率（FE）降低，且MA与血尿酸和尿总蛋白排泄呈正相关。在试验2中，与健康对照相比，IRCU患者的TAS显著降低；低TAS与低血浆尿酸和白蛋白、抗坏血酸、α-生育酚及甲状旁腺激素不变，但FE-尿酸和磷排泄增加有关；后者与TAS呈负相关。在试验3中，与对照相比，IRCU患者的血浆矿物质显著降低，钙/磷、（钙/磷）/镁和（钙/磷）/钠摩尔比增加；红细胞中后者的比率也增加，且与血浆中相同比率高度正相关。
在IRCU中，1）原位肾结石与高空腹血尿酸、高次黄嘌呤尿症和蛋白尿以及高MA相结合，表明全身代谢异常是结石形成的基础；2）抗氧化剂缺乏很常见，与结石的有无无关，但显然与肾脏尿酸再循环不良、低血尿酸和低白蛋白血症、尿磷排泄增加以及低MA有关；3）血浆TAS低、尿液、血浆和红细胞中钙/磷及其他矿物质比率紊乱，但尿钙盐过饱和度不变，这与磷酸钙固体和钙微结石在氧化损伤细胞内形成的观点相符。
