Gupta Deepashree, Brietzke Stephen, Hayden M R, Kurukulasuriya L Romayne, Sowers James R
Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, University of Missouri-Columbia School of Medicine, Columbia, Mo., USA.
Cardiorenal Med. 2011;1(4):261-270. doi: 10.1159/000332388. Epub 2011 Oct 13.
Hyperphosphatemia is a major risk factor for cardiovascular disease, abnormalities of mineral metabolism and bone disease, and the progression of renal insufficiency in patients with chronic renal disease. In early renal disease, serum phosphate levels are maintained within the 'normal laboratory range' by compensatory increases in phosphaturic hormones such as fibroblast growth factor-23 (FGF-23). An important co-factor for FGF-23 is Klotho; a deficiency in Klotho plays an important role in the pathogenesis of hyperphosphatemia, renal tubulointerstitial disease, and parathyroid and bone abnormalities. Clinical hyperphosphatemia occurs when these phosphaturic mechanisms cannot counterbalance nephron loss. Hyperphosphatemia is associated with calcific uremic arteriolopathy and uremic cardiomyopathy, which may explain, in part, the epidemiologic connections between phosphate excess and cardiovascular disease. However, no clinical trials have been conducted to establish a causal relationship, and large, randomized trials with hard endpoints are urgently needed to prove or disprove the benefits and risks of therapy. In summary, hyperphosphatemia accelerates renal tubulointerstitial disease, renal osteodystrophy, as well as cardiovascular disease, and it is an important mortality risk factor in patients with chronic kidney disease.
高磷血症是慢性肾病患者发生心血管疾病、矿物质代谢异常和骨病以及肾功能不全进展的主要危险因素。在早期肾病中，通过成纤维细胞生长因子-23（FGF-23）等排磷激素的代偿性增加，血清磷水平维持在“正常实验室范围”内。FGF-23的一个重要辅助因子是klotho；klotho缺乏在高磷血症、肾小管间质疾病以及甲状旁腺和骨骼异常的发病机制中起重要作用。当这些排磷机制无法抵消肾单位损失时，就会出现临床高磷血症。高磷血症与钙化性尿毒症小动脉病和尿毒症心肌病相关，这可能部分解释了磷过量与心血管疾病之间的流行病学联系。然而，尚未进行临床试验来确立因果关系，迫切需要进行具有硬终点的大型随机试验，以证明或反驳治疗的益处和风险。总之，高磷血症会加速肾小管间质疾病、肾性骨营养不良以及心血管疾病，并且是慢性肾病患者的一个重要死亡风险因素。
