Advances in pharmacotherapy for hyperphosphatemia in renal disease

Introduction: Hyperphosphatemia in chronic kidney disease (CKD) is considered as an independent risk factor for surrogate clinical end points like vascular calcification (VC) and bone disease, or hard clinical outcomes like cardiovascular events. Various treatment options are available for phosphate removal or reduction. Calcium-based phosphate binders (CBB) with their possible positive calcium balance became culprits for progressive VC and increased mortality risk. Non-calcium-based binders (NCBB) treatment allowed a comparable control of hyperphosphatemia with a lower risk of hypercalcemia and a slower progression of VC. Recent data have shown a 22% risk reduction in all-cause mortality with NCBB compared to CBB treatment. The appropriate timing of phosphate binder initiation in CKD patients is still unclear. Recent reports in patients with CKD stages 3b-4 showed increased VC progression when actively treated compared to placebo and a positive calcium, but no negative phosphate balance.

Areas covered: This review discusses the advantages and disadvantages of the pharmacological options to treat hyperphosphatemia.

Expert opinion: The use of phosphate binders is essential in preventing morbidity and mortality in dialysis patients. The choice of phosphate binder takes into account CKD stage, the presence of other components of CKD-mineral and bone disorders, concomitant therapies and drug side-effect profile.     

互动式护理干预对血透高磷血症患者治疗效果及生活质量的影响

目的探讨互动式护理干预在血透高磷血症患者中的应用效果。方法将60例血透合并有高磷血症患者随机分为观察组和对照组,对照组采用常规护理指导,观察组采用互动式护理干预,干预3个月后,比较2组相关知识掌握情况、治疗效果以及生活质量。结果观察组在疾病知识、饮食知识、服药知识等方面的得分均高于对照组,干预后3个月的血磷、钙磷乘积均低于对照组,差异有统计学意义(P0.05)。观察组的生理因子、心理因子、环境因子、社会因子以及生活质量总分均高于对照组,差异有统计学意义(P0.05)。结论互动式护理干预能够提高护理指导的效果,改善血透高磷血症患者的血磷水平和生活质量。     

Hyperphosphatemia,Phosphoprotein Phosphatases,and Microparticle Release in Vascular Endothelial Cells

Hyperphosphatemia in patients with advanced CKD is thought to be an important contributor to cardiovascular risk, in part because of endothelial cell (EC) dysfunction induced by inorganic phosphate (Pi). Such patients also have an elevated circulating concentration of procoagulant endothelial microparticles (MPs), leading to a prothrombotic state, which may contribute to acute occlusive events. We hypothesized that hyperphosphatemia leads to MP formation from ECs through an elevation of intracellular Pi concentration, which directly inhibits phosphoprotein phosphatases, triggering a global increase in phosphorylation and cytoskeletal changes. In cultured human ECs (EAhy926), incubation with elevated extracellular Pi (2.5 mM) led to a rise in intracellular Pi concentration within 90 minutes. This was mediated by PiT1/slc20a1 Pi transporters and led to global accumulation of tyrosine- and serine/threonine-phosphorylated proteins, a marked increase in cellular Tropomyosin-3, plasma membrane blebbing, and release of 0.1- to 1-μm-diameter MPs. The effect of Pi was independent of oxidative stress or apoptosis. Similarly, global inhibition of phosphoprotein phosphatases with orthovanadate or fluoride yielded a global protein phosphorylation response and rapid release of MPs. The Pi-induced MPs expressed VE-cadherin and superficial phosphatidylserine, and in a thrombin generation assay, they displayed significantly more procoagulant activity than particles derived from cells incubated in medium with a physiologic level of Pi (1 mM). These data show a mechanism of Pi-induced cellular stress and signaling, which may be widely applicable in mammalian cells, and in ECs, it provides a novel pathologic link between hyperphosphatemia, generation of MPs, and thrombotic risk.     

碳酸镧与碳酸钙对高磷血症血液透析患者成纤维细胞生长因子-23影响的比较

目的 比较碳酸镧和碳酸钙对血液透析高磷血症患者血清成纤维细胞生长因子-23(FGF-23)水平的影响.方法 56例慢性肾衰竭维持性血液透析患者,血清磷＞1.78 mmol/L、血清钙＜2.38 mmol/L、白蛋白＞30 g/L,限制饮食中磷摄入量约为1 000mg/d.患者随机分为碳酸镧组和碳酸钙组,分别接受碳酸镧或碳酸钙治疗16周.每2周常规检测血清钙、血清磷水平.在治疗第0、8和16周检测血清FGF-23及全段甲状旁腺素(iPTH)水平.结果 碳酸镧和碳酸钙能降低血磷水平.两组血清校正钙离子和iPTH水平无明显变化.与碳酸钙相比,碳酸镧能有效降低FGF-23,并且血清磷与血清FGF-23水平的改变呈正相关.结论 在血液透析患者中应用碳酸镧可以有效降低血清磷及血清FGF-23,而应用碳酸钙并不能减少血清FGF-23.     

烟酰胺联合司维拉姆治疗血液透析高磷血症的临床研究

目的 探讨烟酰胺片联合碳酸司维拉姆片治疗血液透析高磷血症的临床疗效。方法 选取2016年3月—2017年3月在云阳县人民医院肾内科维持血液透析的高磷血症患者100例作为研究对象,所有患者随机分为对照组和治疗组,每组各50例。对照组患者餐中口服碳酸司维拉姆片,用量根据具体血磷水平进行调整（当血磷≥2.41 mmol/L,口服剂量为1 600 mg/次;当血磷<2.41 mmol/L,口服剂量为800 mg/次）,3次/d;治疗组患者在对照组治疗的基础上口服烟酰胺片,500 mg/次,1次/d。两组患者均连续治疗2个月。观察两组患者的临床疗效,比较治疗前后的血清学指标、冠状动脉钙化积分（CACS）、白细胞介素-6（IL-6）和甲状旁腺激素（PTH）水平。结果 治疗后,对照组和治疗组的临床总有效率分别为78.00%、94.00%,两组比较差异具有统计学意义（P<0.05）。治疗后,两组患者的血磷、钙磷乘积水平均显著降低,血钙水平显著升高,同组治疗前后比较差异具有统计学意义（P<0.05）;且治疗后治疗组血清学指标显著优于对照组,两组比较差异具有统计学意义（P<0.05）。治疗后,两组患者的CACS、IL-6、PTH水平均显著降低,同组治疗前后比较差异具有统计学意义（P<0.05）;且治疗后治疗组患者CACS、IL-6、PTH水平显著低于对照组,两组比较差异具有统计学意义（P<0.05）。结论 烟酰胺片联合碳酸司维拉姆片治疗血液透析高磷血症患者疗效显著,可显著降低血磷水平,减轻炎性反应,安全性较高,具有一定的临床推广应用价值。     

马尔可夫模型评价三种磷结合剂治疗高磷血症的研究

目的：评价碳酸钙、碳酸镧和盐酸司维拉姆三者在治疗高磷血症方面的经济性。方法：通过构建马尔可夫模型进行成本效果评价。结果：碳酸镧降磷效果最好,盐酸司维拉姆次之,碳酸钙最差,但考虑成本之后碳酸钙为最优方案。结论：在3倍人均GDP为支付阈值的条件下碳酸钙是最具有成本效果优势的方案。     

Diagnosis of renal osteodystrophy

Chronic Kidney Disease (CKD) is commonly associated with alterations in bone and mineral metabolism (renal osteodystrophy). To date, bone biopsy remains the gold standard for the diagnosis and classification of the various types of renal osteodystrophy, namely: osteitis fibrosa, mixed uremic osteodystrophy, osteomalacia, aplastic and adynamic bone disease. However, due to its invasive nature and the fact that it is quite expensive, there has been a clamor for a search for other tests. Traditionally, the level of parathyroid hormone (PTH) has been considered a surrogate of bone turnover. At this time, the search continues for a specific and sensitive biochemical marker for monitoring bone turnover in CKD., e.g., alkaline phosphatase, osteocalcin, collagen degradation products, etc. In this chapter, we also present the common radiographic findings that are commonly seen in patients with renal osteodystrophy. Other radiographic techniques such as, dual energy x-ray absorptiometry (DEXA) and deferoxamine challenge test (DFO) are also briefly discussed.     

碳酸镧对维持透析患者高磷血症的疗效分析

目的探讨碳酸镧对维持透析患者高磷血症的短期疗效及耐受性。方法回顾性分析2012年10月²013年10月在我院使用碳酸镧治疗高磷血症透析患者(血液透析或腹膜透析)的临床资料。结果共入组22例患者,其中男13例,女9例,腹膜透析4例,血液透析18例,平均年龄(54.2±15.1)岁,平均透析龄(51.5±21.4)月。治疗前、治疗12周后血磷,血清校正钙、钙磷乘积、iPTH为:(2.94±0.43)vs(2.31±0.39)(p=0.00),(2.23±0.11)vs(2.26±0.10)(p=0.25),(82.2±12.9)vs(65.3±11.1)(p=0.00),(1 462±1 053)vs(1 411±943)(p=0.51)。不良反应主要为胃肠道反应,发生率36.4%,无1例患者因严重不良反应退出。结论碳酸镧是一种对维持透析患者短期疗效好、不良反应轻,耐受性良好的口服磷结合剂。