慢性肾脏病高磷血症肾损伤机制的研究进展

高磷血症是慢性肾脏病（CKD）的特征之一。在CKD早期,肾功能下降,单个肾单位对磷的排泄增加使血磷水平维持在正常范围内。随着CKD进展,估算的肾小球滤过率（e GFR）进一步下降到25-30 ml/min,磷代谢失代偿,患者出现高磷血症-[1,2]。血磷升高会加快CKD的进展,并与慢性肾脏病患者死亡率密切相关-[3,4]。Lee等-[5]研究发现,在没有证据表明肾功能有异常的患者中,     

肾脏病磷代谢紊乱的机制和防治

人体磷平衡主要决定于饮食摄入、体内利用及肾脏排泄。饮食中的磷含量、甲状旁腺素及活性维生素D可通过调节肠道及肾脏钠磷转运子表达维持血磷在恒定的水平。慢性肾功能不全患者在肾功能减退初期,甲状旁腺素及成纤维细胞生长因子23(FGF-23)升高可促进磷从肾脏排泄不表现出高磷,后期由于肾单位进一步减少而呈现高磷状态,高磷血症已被证明与心血管事件的发生和死亡率有着密切的关系。目前高磷血症在国内透析患者中的发生率居高不下,同时由于国内缺乏透析营养师、透析剂量相对不足、新型磷结合剂未普及等诸多原因,致使高磷血症的治疗效果较差。传统降磷治疗手段包括限磷饮食、应用磷结合剂和透析清除,而量化评估透析患者磷代谢各个环节,有针对性的开展个体化治疗方案将是解决高磷血症难题的关键。本文将围绕正常磷代谢、慢性肾病患者磷代谢异常以及高磷血症治疗策略的新进展进行讨论。     

慢性肾脏病高尿酸血症治疗的争论和进展

慢性肾脏病(CKD)肾功能不全是产生继发性高尿酸血症的最常见病因,不过此时机体常能通过增加残存肾单位对尿酸的排泄、增加肾小管排泌和减少重吸收,以及肠道细菌对尿酸的降解,降低血尿酸水平.同位素标记示踪试验显示,肾功能不全时尿酸的肾外清除量可占体内产生量的65%,而将血尿酸水平常保持在595 μmol/L以下[1].     

慢性肾脏病的心血管并发症

慢性肾脏病的心血管并发症包括左心室肥大、动脉粥样硬化和动脉硬化；在慢性肾脏病的早期往往已出现心血管并发症。随着肾功能的衰退死于心血管并发症者多于发展成终末期肾病者。慢性肾脏病所以心血管病发生率高，除与传统的危险因素如高血脂、糖尿病等有关外，血尿、蛋白尿、贫血、钙磷失调等尿毒症相关因素发挥了重要作用。因此。早期开展对传统和尿毒症相关危险因素的治疗意义重大。     

慢性肾脏病的心血管并发症

慢性肾脏病的心血管并发症包括左心室肥大、动脉粥样硬化和动脉硬化 ;在慢性肾脏病的早期往往已出现心血管并发症 ,随着肾功能的衰退死于心血管并发症者多于发展成终末期肾病者。慢性肾脏病所以心血管病发生率高 ,除与传统的危险因素如高血脂、糖尿病等有关外 ,血尿、蛋白尿、贫血、钙磷失调等尿毒症相关因素发挥了重要作用。因此 ,早期开展对传统和尿毒症相关危险因素的治疗意义重大。     

中医对慢性肾脏病高同型半胱氨酸血症认识探讨

<正>同型半胱氨酸[1](homocysteine,Hcy)为蛋氨酸循环的正常代谢产物,是能量代谢和许多需甲基化反应的重要中间产物,其本身并不参与蛋白质的合成。Hcy水平受遗传、营养状态、药物、肝肾功能、生活习惯等多种因素影响[2]。越来越多的研究证实,高同型半胱氨酸血症(Hyperhomocysteinemia,HHcy)[3,4]与心脑血管病、骨质疏松、妊娠并发症、痴呆、肿瘤等相     

急性肾损伤转化为慢性肾脏病的机制及治疗进展

<正>肾脏具有较强代偿能力,急性肾损伤(acute kidney disease,AKI)后即使血清肌酐恢复至AKI前的基线水平,但是肾功能和结构没有完全得到修复。AKI的长期预后极差,对AKI患者10年的随访发现,19%~31%的AKI患者最终演变为CKD或终末期肾脏病(end stage renal disease,ESRD),12.5%的患者需要长期依赖透析维持生命。美国肾脏数据系统(USRDS)表明AKI在引起终末期肾病的病因里所占比重逐渐增长[1]。更多     

磷的代谢与慢性肾脏病

<正>磷元素含量在人体内位列第二,85%存在于骨组织,14%存在于其他组织的细胞内,1%存在于细胞外液,磷以磷酸根(PO3-4)形式存在于生物体,参与细胞功能的维持和代谢[1]。在细胞内,磷脂是细胞膜的重要组成部分,参与DNA和RNA的形成,三磷酸腺苷与能量代谢密切相关,磷酸化则是细胞内信号转导的重要途径[2]。临床上所熟知的血磷是指指无机磷酸盐中所包含的磷,正常范围是0.80~1.45 mmol/L。磷平衡     

Epidemiology and prevention of cardiovascular complication in chronic kidney disease patients

The risk for cardiovascular disease is significantly higher among patients with chronic kidney disease (CKD) than among the general population, considering that cardiovascular disease is the prominent cause of both morbidity and mortality in dialysis patients. This is explained mainly by the considerable prevalence of cardiovascular risk factors among CKD patients since the earliest stages of renal impairment, which include not only the so-called traditional risk factors, but also a number of additional risk factors that are specific to CKD and to the dialytic treatment itself. Considering the multiplicity of cardiovascular risk factors operating in CKD patients, as well as the crucial impact of their cardiovascular condition on long-term outcome, it is mandatory that all the available interventions aimed at the correction of all the modifiable risk factors for cardiovascular disease are performed as early as possible in the progression of the disease. In particular, the results of several controlled clinical trials have shown that a timely correction of anemia and of calcium-phosphate disorders leads to a significant improvement in the cardiovascular conditions of CKD patients. Evidence also is growing regarding the benefits of intervention of newly recognized risk factors for cardiovascular disease such as inflammation and oxidant stress.     

慢性肾脏疾病非透析患者高磷血症的管理

高磷血症是慢性肾脏病(chronic kidney disease,CKD)患者的重要并发症之一。血磷水平长期过高可导致甲状旁腺功能亢进、肾性骨营养不良、血管钙化等多种并发症,而且与病死率增加密切相关。控制血磷水平达标可有效改善CKD患者的预后。本文将结合最新研究成果进一步探讨高磷血症的发生机制、疾病危害,以及非透析高磷血症患者的临床监测路径和治疗方法,为临床工作提供参考。     

New developments in the management of hyperphosphatemia in chronic kidney disease

Hyperphosphatemia is a characteristic complication of significant chronic kidney disease. Elevated serum phosphorous is associated with reduced survival. Hyperphosphatemia has long been recognized as predisposing to uremic bone disease and disorders of parathyroid function. Furthermore, elevated serum phosphate has been implicated particularly in the development of cardiovascular structural and functional abnormalities. Given the limitations of restricting phosphate in the diet and the inadequate removal by conventional dialysis regimes, nephrologists rely on the use of additional medications to control serum levels (currently oral phosphate binders). This review focuses on new agents and therapeutic approaches dealing with hyperphosphatemia in chronic kidney disease, that are not currently licensed and available in routine clinical practise. This article attempts to review therapies under development and considers additional effects that the next generation of agents may bring over and above those already within the therapeutic armamentarium.     

慢性肾脏病急性加重的诊治与预防

慢性肾脏病(CKD)是对健康产生影响的肾脏结构或功能异常>3个月的总称。多数CKD缓慢进展,但在有效血容量不足、感染、使用肾毒性药物等危险因素影响下可急性加重。详细的病史、清楚的病程、规律的随访和肾脏的大小有利于鉴别诊断。积极治疗原发病、避免和纠正CKD进展的危险因素,预防和及时发现并积极清除CKD急性加重的危险因素,有助于肾功能保持稳定。     

Treatment of hyperphosphatemia in patients with chronic kidney disease on maintenance hemodialysis

Treatment of hyperphosphatemia in patients with chronic kidney disease on maintenance hemodialysis. Hyperphosphatemia in patients with ESRD leads to secondary hyperparathyroidism, renal osteodystrophy, and is independently associated with mortality risk. The exact mechanism by which hyperphosphatemia increases mortality risk is unknown, but it may relate to enhanced cardiovascular calcification. National Kidney Foundation K/DOQI bone metabolism and disease guidelines recommend maintenance of serum phosphorus (P) below 5.5 mg/dL, and Ca x P product less than 55 mg(2)/dL(2). Although calcium-based phosphate binders (CBPB) are cost effective, long-term safety concerns relate to their postulated role in progression of cardiovascular calcification. Sevelamer hydrochloride has been recommended as an alternative noncalcium phosphate binder. Results from the Calcium Acetate Renagel Evaluation (CARE study) indicate that calcium acetate is more effective than sevelamer in controlling serum phosphorous and Ca x P product in hemodialysis patients. In the Treat-to-Goal study, dialysis patients treated with sevelamer had slower progression of coronary and aortic calcification than patients treated with CBPB. The mechanism underlying the beneficial effect of sevelamer is unknown, but may relate to decreased calcium loading or to dramatic reductions in LDL cholesterol in sevelamer-treated patients. At present, evidence incriminating CBPB in the progression of cardiovascular calcification in ESRD remains largely circumstantial. As calcium acetate is more efficacious and cost effective than sevelamer, it remains an accepted first-line phosphate binder. In this review, we will examine these issues and provide rational guidelines for the use of calcium-based phosphate binders in patients on maintenance hemodialysis.     

An introduction to phosphate binders for the treatment of hyperphosphatemia in patients with chronic kidney disease

Chronic kidney disease has the potential to induce sequelae that can have severe and mortal outcomes. In particular, impaired glomerular filtration can cause a hyperphosphatemic state, which, if left unchecked, can lead to secondary hyperparathyroidism, vascular calcification, and renal osteodystrophy. Therapeutic management of hyperphosphatemia must maintain both phosphorus and calcium serum concentrations within the recommended guidelines. The balance of both minerals is regulated by parathyroid hormone; thus, an imbalance of one affects the other. In end-stage renal disease, patients often present with hypocalcemic levels due to the kidneys' inability to generate active vitamin D to promote calcium absorption in the intestine. Absorption of calcium can be increased by the administration of active vitamin D analogues. Minimizing phosphorus intake through a strict dietary regimen, combined with the use of phosphate binders to absorb excess ingested phosphate, can help to maintain serum phosphate levels near the recommended concentration of 5.5 mg/dL. Phosphate-binding compounds have evolved from the original aluminum-based binders pioneered in the 1970s to calcium-based binders such as calcium acetate, and more recently, to the following additions to the nephrologist's armamentarium: sevelamer--a polyhydrochloride polymer, and lanthanum carbonate. One of the top 2 common clinical treatments for hyperphosphatemia, calcium acetate, has an established history of efficacy since the 1980s, and has been shown to be cost effective and well tolerated, as well.     

A new approach to the evaluation of hyperphosphatemia in chronic kidney disease

AIMS: Hyperphosphoremia, main contributor to cardiovascular calcifications, has a major impact on the morbidity and mortality of chronic renal failure (CRF) patients. Phosphate binders and dietary phosphate limitation are not effective enough to abolish hyperphosphoremia-induced cardiovascular abnormalities, therefore, the identification of other and more timely approaches for serum phosphorous reduction is necessary. Salivary fluid contains phosphate which, if related to the daily salivary secretion (1,000 - 1,800 ml), deserves attention as a marker for an earlier start of pharmacologic treatment for phosphorous removal. In ESRD patients under dialysis we have shown increased salivary phosphate closely to be related with serum phosphorous and interpreted as compensatory. This study evaluates salivary phosphate secretion in 77 nondialyzed CRF compared with healthy subjects and its relationship with renal function. METHODS: Saxon's test confirmed normal salivary function in patients and controls. Serum phosphorous, creatinine and GFR were also measured. RESULTS: Salivary phosphorous was significantly higher in CRF patients compared with controls: 38.60 mg/dl (range 12.20 - 95.60) vs 16.30 (10.30 - 27.10), p < 0.0001; serum phosphate was also significantly higher: 3.70 (2.10 - 6.80) vs 3.50 (2.3 4.6), p = 0.013. In CRF patients, salivary phosphorous positively correlated with serum phosphorous (r - 0.45, p < 0.0001) and with serum creatinine (r = 0.72, p < 0.0001), while negatively correlated with GFR (r = -0.72, p < 0.0001). CONCLUSIONS: The results of our study show also in CRF patients increased salivary phosphate secretion, which is related with renal function. On this basis the use of salivary phosphate secretion as a marker for an earlier start of the abnormal phosphate, metabolism pharmacologic treatment could be proposed.     

迎接挑战，扎实工作，实现慢性肾脏病防治的优化

不久前，国际肾脏病学会（ISN）和国际肾脏基金联合会（IFKF）联合发出倡议，将每年3月份的第2个星期四（今年是3月9日）定为“世界肾脏日”。正如ISN和IFKF倡议中所说，设立“世界肾脏日”的主要目的，就是要在全世界敲起警钟．唤起全人类对慢性肾脏病（CKD）的高度关注。稍后，中华医学会肾脏病学分会也发出倡议，并举办了一系列有关活动，倡议政府官员、社会各界、大众媒体、全体医药卫生人员乃至每个家庭和个人，都来关注和重视CKD的预防和治疗，为提高国人健康水平和生活质量而共同奋斗。