Baggio B, Budakovic A, Nassuato M A, Vezzoli G, Manzato E, Luisetto G, Zaninotto M
Division of Nephrology, Department of Medical and Surgical Sciences, University of Padua, Italy.
Kidney Int. 2000 Sep;58(3):1278-84. doi: 10.1046/j.1523-1755.2000.00283.x.
Reports of an increase in plasma and erythrocyte phospholipid arachidonic acid content and in urinary prostaglandin E2 (PGE2) excretion in patients with idiopathic calcium nephrolithiasis suggested their crucial role in the pathogenesis of hypercalciuria, a well-known risk factor for lithogenesis.
To confirm this hypothesis, 15 healthy subjects and 20 nephrolithiasis patients were evaluated for plasma phospholipid polyunsaturated fatty acid content and PGE2 concentration, serum parathyroid hormone, 25 hydroxyvitamin D3, 1, 25-dihydroxyvitamin D3, and bone-specific alkaline phosphatase levels, as well as urinary excretion of calcium, biochemical markers of bone resorption (hydroxyproline and crossLaps), and intestinal calcium absorption. Furthermore, the effect of a 30-day fish-oil diet supplementation on the previously mentioned parameters was investigated in the patients.
At baseline, patients compared with controls showed higher levels of plasma phospholipid arachidonic acid content (P = 0.002), PGE2 (P = 0.0004), serum 25-vitamin D3 (P = 0.001), and 1,25-vitamin D3 (P = 0.001), urinary excretion of calcium (P = 0.001), hydroxyproline (P = 0.007), and crossLaps (P = 0.019), as well as intestinal calcium absorption (P = 0.03 at 60 min). Fish oil supplementation induced a reduction in the plasma phospholipid arachidonic acid level (P < 0.0001), and except for serum concentrations of 25-vitamin D3, normalized baseline blood and urinary parameters, including intestinal calcium absorption. A close correlation between plasma PGE2 and serum 1,25-vitamin D3 (P = 0.004) and between phospholipid arachidonic acid and intestinal calcium absorption (P = 0.0002) and calciuria (P = 0.007) was observed, as well as between urine excretion of crossLaps and hydroxyproline (P < 0.0001), crossLaps and calcium (P < 0.0001), and hydroxyproline and calcium (P < 0.0001).
These findings indicate that the phospholipid arachidonic acid content anomaly could represent the primary event responsible for the mosaic of metabolic and clinical alterations that are distinctive features of renal stone formers, and suggest that a common pathogenetic mechanism might account for the several forms of hypercalciuria detected in idiopathic calcium nephrolithiasis.
特发性钙肾结石患者血浆和红细胞磷脂花生四烯酸含量增加以及尿前列腺素E2（PGE2）排泄增加的报告表明，它们在高钙尿症的发病机制中起关键作用，高钙尿症是结石形成的一个众所周知的危险因素。
为了证实这一假设，对15名健康受试者和20名肾结石患者进行了评估，检测其血浆磷脂多不饱和脂肪酸含量和PGE2浓度、血清甲状旁腺激素、25-羟基维生素D3、1,25-二羟基维生素D3和骨特异性碱性磷酸酶水平，以及尿钙排泄、骨吸收生化标志物（羟脯氨酸和交联C-末端肽）和肠道钙吸收情况。此外，还研究了患者补充30天鱼油饮食对上述参数的影响。
在基线时，与对照组相比，患者的血浆磷脂花生四烯酸含量（P = 0.002）、PGE2（P = 0.0004）、血清25-维生素D3（P = 0.001）和1,25-维生素D3（P = 0.001）、尿钙排泄（P = 0.001）、羟脯氨酸（P = 0.007）和交联C-末端肽（P = 0.019）水平以及肠道钙吸收（60分钟时P = 0.03）均较高。补充鱼油可使血浆磷脂花生四烯酸水平降低（P < 0.0001），除血清25-维生素D3浓度外，可使基线血液和尿液参数（包括肠道钙吸收）恢复正常。观察到血浆PGE2与血清1,25-维生素D3之间（P = 0.004）、磷脂花生四烯酸与肠道钙吸收之间（P = 0.0002）以及与尿钙排泄之间（P = 0.007）存在密切相关性，同时交联C-末端肽与羟脯氨酸的尿排泄之间（P < 0.0001）、交联C-末端肽与钙之间（P < 0.0001）以及羟脯氨酸与钙之间（P < 0.0001）也存在密切相关性。
这些发现表明，磷脂花生四烯酸含量异常可能是导致肾结石患者特有的代谢和临床改变的主要原因，并提示一种共同的发病机制可能解释特发性钙肾结石中检测到的几种高钙尿症形式。
