高磷血症维持性血液透析患者的临床分析

目的:比较不同血磷水平的维持性血液透析的尿毒症患者的临床表现和实验室指标,探讨其临床意义。方法:选择上海交通大学医学院附属新华医院(崇明)肾内科28例高血磷(SP>1.6mmol/L)的维持性血液透析患者为病例组,30例血磷正常(SP≤1.6mmol/L)维持性血液透析患者为对照组,比较两组患者的原发病组成,年龄,性别,透析龄,皮肤瘙痒发生率,腰背痛发生率,血钙,血碳酸氢根,血红蛋白,红细胞压积,血碱性磷酸酶,肾功能,血浆白蛋白水平及左心室肥厚发生率。结果:病例组与对照组在原发病组成,年龄(43.2±9.8岁vs 40.5±12.2岁),男女性别比例(16/12 vs.17/13),透析龄(32.56±6.71月vs.35.43±5.82月)等方面无显著性差异(P>0.05),有可比性,在血红蛋白(83.22±6.71g/L vs 103.36±5.84g/L),红细胞压积(24.83±1.92%vs.30.76±1.52%),血钙(1.71±0.16mmol/L vs.2.23±0.21 mmol/L),血碳酸氢根(14.2±3.1mmol/L vs 20.6±4.9 mmol/L),血碱性磷酸酶(124.26±16.33U/L vs.61.47±14.91 U/L),皮肤瘙痒发生率(22/28 vs.7/30),腰背痛发生率(19/28 vs.6/30),左心室肥厚发生率(20/28 vs 12/30),有显著性差异(P<0.05),肌酐(956±142mmol/L vs.923±156 mmol/L),尿素氮(23.1±6.3mmol/L vs.24.8±8.9mmol/L),血浆白蛋白(30.5±3.8g/L vs.31.2±2.9g/L),无显著性差异(P>0.05)。结论:伴有高磷血症的维持性血液透析患者与血磷正常的患者相比,血碱性磷酸酶,皮肤瘙痒发生率,腰背痛发生率及左心室肥厚发生率较高,而血钙,血碳酸氢根,血红蛋白及红细胞压积较低,有一定差异。     

低钙透析液联合醋酸钙对血液透析患者高磷血症的影响

目的：研究低钙透析液联合醋酸钙治疗对血液透析患者血磷、血钙及甲状旁腺激素iPTH水平的影响。方法：将30例维持性血液透析患者随机分为试验组和对照组,在试验期间所有患者均低磷饮食,两组透析液钙浓度均为1．25mmol／L,试验组同时给予醋酸钙治疗,对照组不应用醋酸钙治疗,三个月后观察和比较两组患者的血钙、血磷及血iPTH水平的变化。结果：治疗前,两组各组血磷、血钙、血磷和血iPTH的水平比较差异均无统计学意义（P〉0．05）。治疗后,对照组血钙水平明显下降（P〈0．05）,血iPTH水平略上升但无统计学意义（P〉0．05）,血磷水平无显著变化（P〉0．05）;试验组血iPTH水平略下降（P〉0．05）,血钙水平无明显变化（P〉0．05）,但血磷明显下降（P〈0．05）;且试验组血磷水平较对照组明显下降（P〈0．05）,血钙水平显著高于对照组（P〈O．05）,但在正常范围内,两组血iPTH水平比较无统计学意义（P〉0．05）。结论：低钙透析液联合醋酸钙治疗可有效降低血液透析患者的血磷水平,且不会导致高钙血症的发生。     

High phosphate feeding induced arterial medial calcification in uremic rats: Roles of Lanthanum carbonate on protecting vasculature

Aims

High cardiovascular mortality in patients with end-stage renal disease is closely associated with arterial medial calcification (AMC) caused by hyperphosphatemia, the mechanism of which associated hormones (FGF-23, klotho) and osteochondrogenic events is unclear. We examined the effect of Lanthanum carbonate on AMC via regulating the abnormalities in phosphorus metabolism of uremic rats.

Main methods

45 healthy SD rats were randomly divided into 3 groups: Normal group (n = 15), CRF group (n = 15), CRF diet supplemented with 2% La (n = 15). AMC in great arteries were evaluated by VonKossa. Osteochondrogenic specific genes were analyzed by Immunohistochemistry and qRT-PCR. Serum FGF-23 and klotho levels were detected by ELISA kit.

Key findings

Serum phosphate was markedly increased in CRF group (6.94 ± 0.97 mmol/L) and 2%La group (5.12 ± 0.84 mmol/L) at week 4, while the latter became hypophosphatemic (2.92 ± 0.73 mmol/L vs CRF group, p < 0.01) at week 10. Inhibitory effect of 2%La on development of AMC was reflected by downregulated Runx2, Osterix, BSP, Osteocalcin and collagenII and a reduction of FGF-23 at week 4(vs CRF group, p < 0.01) but not week 10.

Significance

Beneficial effects of Lanthanum carbonate on progression of AMC in CRF could be mainly due to the decreased phosphate retention and FGF-23 in early stage and likewise a reduction of bone-associated proteins via osteochondrogenic pathway. Lanthanum carbonate has no effect on soluble klotho and serum FGF-23 in late stage of CRF.     

Microtubule stabilization attenuates vascular calcification through the inhibition of osteogenic signaling and matrix vesicle release

Vascular calcification is a strong predictor of cardiovascular morbidity and mortality, especially in individuals with chronic kidney disease or diabetes. The mechanism of vascular calcification has remained unclear, however, and no effective therapy is currently available. Our study was aimed at identifying the role of dynamic remodeling of microtubule cytoskeletons in hyperphosphatemia-induced vascular calcification. Exposure of primary cultures of mouse vascular smooth muscle cells (VSMCs) to inorganic phosphate (Pi) elicited ectopic calcification that was associated with changes in tubulin dynamics, induction of osteogenic signaling, and increased release of matrix vesicles. A microtubule depolymerizing agent enhanced Pi-dependent calcification, whereas microtubule stabilization by paclitaxel suppressed calcification both in VSMC cultures and in an ex vivo culture system for the mouse aorta. The inhibition of Pi-stimulated calcification by paclitaxel was associated with down-regulation of osteogenic signal and attenuation of matrix vesicle release. Our results indicate that microtubule plays a central role in vascular calcification, and that microtubule stabilization represents a potential new approach to the treatment of this condition.     

碳酸镧咀嚼片联合依降钙素对血液透析高磷血症患者冠状动脉钙化及血磷水平的影响

摘要 目的：观察碳酸镧咀嚼片联合依降钙素对血液透析高磷血症患者冠状动脉钙化及血磷水平的影响。方法：选取2019年8月~2021年3月我院接收的血液透析高磷血症患者120例,采用双色球法,将患者分为对照组（60例,依降钙素治疗）和观察组（60例,在对照组基础上结合碳酸镧咀嚼片治疗）,对比两组疗效、血磷、血钙、钙磷乘积、全段甲状旁腺激素（iPTH）、成纤维生长因子23（FGF-23）、冠状动脉钙化积分（CACS）,观察两组不良反应发生情况。结果：观察组临床总有效率（91.67%）优于对照组（70.00%）（P<0.05）。两组不良反应发生率组间对比无差异（P>0.05）。观察组治疗结束后血磷、iPTH、血钙、FGF-23、钙磷乘积、CACS低于对照组（P<0.05）。结论：血液透析高磷血症患者采用碳酸镧咀嚼片联合依降钙素治疗,可延缓冠状动脉钙化,有效降低血磷水平,安全有效。     

高磷血症维持性血液透析患者的临床分析

目的：比较不同血磷水平的维持性血液透析的尿毒症患者的临床表现和实验室指标,探讨其临床意义。方法：选择上海交通大学医学院附属新华医院（崇明）肾内科28例高血磷（SP〉1．6mmol／L）的维持性血液透析患者为病例组,30例血磷正常（SPN1．6mmol／L）维持性血液透析患者为对照组,比较两组患者的原发病组成,年龄,性别,透析龄,皮肤瘙痒发生率,腰背痛发生率,血钙,血碳酸氢根,血红蛋白,红细胞压积,血碱性磷酸酶,肾功能,血浆白蛋白水平及左心室肥厚发生率。结果：病例组与对照组在原发病组成,年龄（43．2±9．8岁VS40．5±12．2岁）,男女性别比例（16／12vs．17／13）,透析龄（32．56±6．71月vs．35．43±5．82月）等方面无显著性差异（P〉o．05）,有可比性,在血红蛋白（83．22±6．71g／Lvs103．36±5．84g/L）,红细胞压积（24．83±1．92％vs．30．76±1．52％）,血钙（1．71±0．16mmol／Lvs．2．23±0．21mmol／L）,血碳酸氢根（14．2±3．1mmol／Lvs20．6±4．9mmol／L）,血碱性磷酸酶（124．26±16．33U／Lvs．61．47±14．91U/L）,皮肤瘙痒发生率（22／28vs．7／30）,腰背痛发生率（19／28vs．6／30）,左心室肥厚发生率（20／28vs12／30）,有显著性差异（P〈0．05）,肌酐（956±142mmol／LVS．923±156mmol／L）,尿素氮（23．1±6．3mmol／LVS．24．8±8．9retool／L）,血浆白蛋白（30．5±3．8g/Lvs．31．2±2．9g/L）,无显著性差异（P〉0．05）。结论：伴有高磷血症的维持性血液透析患者与血磷正常的患者相比,血碱性磷酸酶,皮肤瘙痒发生率,腰背痛发生率及左心室肥厚发生率较高,而血钙,血碳酸氢根,血红蛋白及红细胞压积较低,有一定差异。     

Blood pressure and heart rate variability are linked with hyperphosphatemia in chronic kidney disease patients

ABSTRACT

Hyperphosphatemia is a common complication of chronic kidney disease (CKD) and is associated with cardiovascular disease (CVD), which has contributed to an increase in mortality of CKD patients. The onset of CVD often varies by time-of-day. Acute myocardial infarction or ventricular arrhythmia occurs most frequently during early morning. Blood pressure (BP) and heart rate circadian rhythms account for the diurnal variations in CVD. Preservation of normal circadian time structure from the cardiomyocyte level to the whole organ system is essential for cardiovascular health and CVD prevention. Independent risk factors, such as reduced heart rate variability (HRV) and increased BP variability (BPV), are particularly prevalent in patients with CKD. Analysis of HRV is an important clinical tool for characterizing cardiac autonomic status, and reduced HRV has prognostic significance for various types of CVD. Circadian BP rhythms are classified as extreme dipper, dipper, non-dipper or riser. It has been reported that nocturnal riser BP pattern contributes to cardiovascular threats. Previous studies have indicated that the circadian rhythm of serum phosphate in CKD patients is consistent with the general population, with the highest diurnal value observed in the early morning hours, followed by a progressive decrease to the lowest value of the day, which occurs around 11:00 am. Rhythm abnormalities have become the main therapeutic target for treating CVD in CKD patients. It has been reported that high levels of serum phosphate are associated with reduced HRV and increased BPV in CKD patients. However, the mechanisms related to interactions between hyperphosphatemia, HRV and BPV have not been fully elucidated. This review focuses on the evidence and discusses the potential mechanisms related to the effects of hyperphosphatemia on HRV and BPV.