慢性肾脏病合理应用活性维生素D及专家共识

慢性肾脏病(CKD)患者普遍存在矿物质和骨代谢紊乱,2005年KDIGO将其定义为:慢性肾脏病相关性矿物质及骨代谢紊乱( CKD - MBD),可表现为钙、磷、甲状旁腺激素(PTH)或维生素D代谢异常,骨转化、矿化、骨容量、骨骼线性生长或骨强度的异常,还可表现为血管或其他软组织钙化.有研究显示,慢性肾脏病患者早期即出现维生素D的减少及矿物质和骨代谢紊乱,并贯穿于肾功能进行性减退的全过程[1,2],常与因血管钙化导致心血管结构和功能的损害有关,并和患者的死亡率和疾病的发生率上升相关[3-5].合理应用活性维生素D不仅可以治疗慢性肾脏病患者出现的矿物质及骨代谢紊乱,还可以降低蛋白尿,减少炎症,降低血压,延缓终末期肾病的进展,提高慢性肾脏病患者的生存质量,降低死亡率[6-9].     

拟钙剂能否替代甲状旁腺切除手术

正慢性肾脏病矿物质与骨异常(CKD-MBD)是指慢性肾脏病(CKD)导致的矿物质及骨代谢异常综合征,临床表现为钙、磷、甲状旁腺素(PTH)或维生素D代谢异常,骨转化、矿化、骨量、骨线性生长或骨强度异常,以及血管、心脏瓣膜等软组织钙化。CKD-MBD严重影响患者的生活质量和预后。预防高血磷、维持血钙正常、控制继发     

中国慢性肾脏病矿物质和骨异常诊治指南概要

正慢性肾脏病(CKD)是一个全球性的健康问题,中国成人CKD患病率已超过10%。慢性肾脏病矿物质与骨异常(CKD-MBD)是CKD的严重并发症,是CKD患者致残、致死等不良结局的重要原因之一,国际上一些肾脏病组织相继制订了一系列指南用于规范CKD-MBD的诊断和治疗。2013年刘志红教授领导的团队制订了《慢性肾脏病矿物质和骨异常诊治指导》,极大地推动了我国肾脏病学家对CKD-MBD的认识和管理水平,对于改变我国CKD-MBD知晓率低、     

硫代硫酸钠治疗慢性肾脏病患者血管钙化临床应用进展

近年来,慢性肾脏病(CKD)作为世界范围内主要的公共卫生问题受到越来越多的关注.慢性肾脏病矿物质和骨异常(CKD-MBD)是由于CKD的矿物质及骨代谢异常综合征所致,严重地影响了 CKD患者的生存率和生活质量.血管钙化是CKD-MBD的临床表现之一,其包括:动脉内膜钙化、中膜钙化、心脏瓣膜钙化和钙化防御.目前临床上还未...     

慢性肾脏病继发性甲状旁腺功能亢进的诊断

慢性肾脏病继发性甲状旁腺功能亢进(简称继发性甲旁亢,SHPT)是由于慢性肾脏病所引起的低血钙、高血磷、活性维生素D合成和分泌减少等因素共同刺激甲状旁腺过度分泌甲状旁腺素而引发的以多系统损害为表现的一组临床综合征.继发性甲旁亢是慢性肾脏病的重要表现之一,其不仅可以引起骨骼的严重损害,而且可以加重钙磷代谢异常,引起皮肤瘙痒、贫血、神经系统损害及心血管疾病等[1-3].因此,将”肾性骨病”这一名词改为慢性肾脏病,因为肾性骨病只是骨病理学改变的一部分[4].     

维生素D制剂在透析患者中的应用

肾性骨病现已更名为"慢性肾脏病-矿物质-骨代谢性疾病"(CKD-MBD),因为它影响的不仅限于骨代谢,还包括心血管系统及其他组织。它是CKD,特别是终末期肾功能衰竭透析患者极为常见的一种代谢异常,其治疗干预措施中维生     

慢性乙型肝炎病毒感染者合并肾、骨损伤的风险及临床管理探讨

乙型肝炎病毒(hepatitis B virus,HBV)感染及核苷(酸)类似物治疗会对肾脏和骨骼造成不同程度的损伤,慢性肾脏病、骨质疏松症等肾骨疾病在逐步老龄化的慢性HBV感染者中日益常见,但目前缺乏应对这一问题的系统指导意见。本文意在阐明HBV感染人群的肾骨疾病风险以期引起临床医师对该人群中这两类合并症的重视,并结合指南推荐、临床实际就此人群的肾脏与骨骼健康状况评估、监测及合并肾骨疾病或其风险较高时的抗病毒治疗提出初步建议供借鉴。     

CKD-MBD的诊断是否必须依赖骨活检

<正>慢性肾脏病(CKD)已成为全球性公共卫生问题,其发病率日益升高,且预后较差。矿物质代谢异常在CKD 2期即已出现,患者如未得到及时诊治,终将发生代谢性骨病(肾性骨营养不良)。2005年,KDICO将肾性骨营养不良重新定义并扩大诊断为慢性肾脏病矿物质和骨异常(CKD-MBD),包括以下三种异常:(1)钙、磷、甲状旁腺激素和维生素D代谢异常;(2)骨转运、骨矿化、骨容量和骨的生长异常;(3)血管和软组织钙化。其中,肾性骨营养不良特指CKD-MBD中经四环素标记骨活检确诊的一类疾病。由于骨活检属于侵     

骨代谢指标在慢性肾脏病-矿物质骨代谢紊乱中的研究进展

慢性肾脏病-矿物质骨代谢紊乱(chronic kidney disease-mineral and bone disorder,CKD-MBD描述了慢性肾脏病(chronic kidney disease,CKD)患者体内钙和磷酸盐稳态的变化,其与钙、磷、甲状旁腺素(parathyroid hormone,PTH)和维生素D的异常循环水平有关,影响了骨矿化、生长和骨强度,导致心血管事件、骨折率及病死率的增加。目前对CKD-MBD的管理主要依赖于对血清钙、磷酸盐和甲状旁腺素浓度等生化指标的临床判断和评估。骨代谢标志物的应用并不广泛。本文主要针对血清骨代谢标志物对慢性肾脏病患者的临床价值做一综述,主要涉及骨特异性碱性磷酸酶(bone-specific alkaline phosphatase,BSAP)、Ⅰ型原胶原前肽(procollagen type-ⅠN terminal propeptide,P1NP)、抗酒石酸磷酸酶5b (tartrate-resistant acid phosphatase 5b,TRACP 5b)、Ⅰ型胶原羧基端肽β特殊序列(β-carboxy I terminal peptide,β-CTX)、成纤维细胞生长因子23 (fibroblast growth factor 23,FGF-23)、Klotho蛋白及硬骨抑素(sclerostin)。     

继发性甲状旁腺功能亢进的治疗与进展

慢性肾脏病矿物质与骨异常(chronic kidney diseasemineral and bone disorder, CKD-MBD)是CKD患者常见并发症之一,是由于CKD导致的矿物质及骨代谢异常综合征。临床上可出现以下1项或多项表现:(1)钙、磷、甲状旁腺激素(parathyroid hormone, PTH)或维生素D代谢异常;(2)骨转化、矿化,骨线性生长或骨强度异常;(3)血管或其他软组织     

关注血管钙化的基础和临床研究

血管钙化是指羟磷灰石矿物质沉积于血管系统的病理过程,临床多见于动脉粥样硬化的斑块、糖尿病、衰老及慢性肾功能衰竭、尿毒症的血管及心脏瓣膜,目前尚缺乏有效的治疗方法。多种机制参与了血管钙化的发生,包括成骨细胞和破骨细胞的标志分子、血管钙化抑制因子、基质囊泡、微核糖核苷酸、钙磷稳态失衡以及血管旁/自分泌活性因子的功能紊乱、氧化应激、内质网应激以及自噬等均参与血管钙化的发生发展。关注和加强血管钙化的基础研究,促进血管钙化的临床转化研究对于揭示血管钙化的发病机制和血管钙化相关疾病的防治具有重要意义。     

Mineral-bone disorder with chronic kidney disease

Mineral-bone disorder in chronic kidney disease is a clinical syndrome provoked by the combination of three factors: abnormal laboratory results, bone morphology disorder and extra-bone calcification. Its onset in adult age is linked with a decrease in glomerular filtration (GF < 1 ml/s). Fully developed forms occur in the course of regular dialysis treatment. The use of the traditional denomination "renal osteodystrophy" is currently restricted to the bone morphology finding. As there are two threshold types of bone turnover (low and high) and two degrees of mineralisation (low and normal), there is a total of four basic variants of mineral-bone disorder. The high turnover variants--secondary hyperparathyreosis and a combined disorder--are still the most frequent and are diagnosed in 70 to 80% of cases. Low turnover disorders include osteomalatia (OM) and adynamic bone disease (ABD). While OM is becoming increasingly rare, the occurrence of ABD is on the rise. The main reason for this may be the steady growth in the age of dialised patients and a number of risk factors, as well as treatment with inadequately high doses of vitamin D. Progressive chronic kidney disease may be linked with D-hormone deficit, negative calcium balance and with positive phosphate balance. Phosphates become a key factor in the development and progression of secondary hyperparathyreosis and extra-bone calcification in the case of D-hormone substitution. Therefore, maintaining a good phosphate balance by restricting their intake or by reducing their intestinal resorption through the use of phosphate binders is the most efficient therapeutic procedure. In patients with chronic kidney failure, adequate dialysis treatment is necessary. Hyperphosphatemia and extra-bone calcification are new independent risk factors of cardiovascular morbidity and mortality.     

Reprint of: Vitamin D receptor activation and prevention of arterial ageing

In chronic kidney disease (CKD) patients, cardiovascular (CV) morbidity and mortality rate is higher than in the general population, because of frequently concomitant hypertension, peripheral vascular disease, heart failure, vascular calcification (VC), diabetes and mineral bone disease. Recently, another important factor associated to CV risk in CKD has been deeply investigated: vitamin D deficiency. Vitamin D Receptors (VDRs) are present in several systems and tissues and VDR activation is associated to positive effects, resulting in better blood pressure control and prevention of diabetic nephropathy. Unfortunately, the natural, non-selective vitamin D receptor activator (VDRA), calcitriol, is associated to higher serum calcium and phosphate levels, thus worsening CV risk in CKD. Recent data showed that the selective VDRA paricalcitol might have ameliorative CV effects. The potential positive impact of the use of paricalcitol on diabetic nephropathy, cardiac disease, hypertension, and VC may open new paths in the fight against CV disease in CKD patients.     

Vitamin D receptor activation and prevention of arterial ageing

In chronic kidney disease (CKD) patients, cardiovascular (CV) morbidity and mortality rate is higher than in the general population, because of frequently concomitant hypertension, peripheral vascular disease, heart failure, vascular calcification (VC), diabetes and mineral bone disease. Recently, another important factor associated to CV risk in CKD has been deeply investigated: vitamin D deficiency. Vitamin D Receptors (VDRs) are present in several systems and tissues and VDR activation is associated to positive effects, resulting in better blood pressure control and prevention of diabetic nephropathy. Unfortunately, the natural, non-selective vitamin D receptor activator (VDRA), calcitriol, is associated to higher serum calcium and phosphate levels, thus worsening CV risk in CKD. Recent data showed that the selective VDRA paricalcitol might have ameliorative CV effects. The potential positive impact of the use of paricalcitol on diabetic nephropathy, cardiac disease, hypertension, and VC may open new paths in the fight against CV disease in CKD patients.     

K/DOQI clinical practice guidelines for management of renal osteodystrophy in predialysis patients

Blood levels of PTH (parathyroid hormone) begin to rise when GFR falls below 60 mL/min/1.73 m2, and evidence of bone disease due to hyperparathyroidism may be present at Stage 3 of chronic kidney disease (CKD). IntactPTH(i-PTH) is a useful test in detecting high turnover bone disorder and low turnover bone disorder. The Work Group taken target range of serum i-PTH in predialysis patients by their opinion. Dietary phosphorus should be restricted when the serum levels of i-PTH are elevated above target range of CKD stage. If phosphorus and i-PTH levels can not be controlled within the target range, despite dietary phosphorus restriction, phosphate binders should be prescribed. Only calcium based phosphate binders are available in predialysis patients in Japan. To avoid soft tissue calcification, total elemental calcium intake should not exceed 2,000 mg/day. If vitamin D deficiency are present, vitamin D2 should be supplied. But we can't measure serum 25(OH) D and prescribe vitamin D2 in Japan. Low dose of active vitamin D sterols are effective on renal osteodystrophy in predialysis patient. Active vitamin D sterols should be prescribed from low doses and serum calcium levels and renal function should be checked frequently. It is necessary to evaluate this K/DOQI (Kidney disease outcomes quality initiative) guideline and to establish guideline in Japan.     

High-turnover-Osteodystrophie

In chronic kidney disease hyopcalcemia (low levels of vitamin D and reduced calcitriol synthesis in the kidney) and hyperphosphatemia increase parathyroid hormone (PTH) levels. Over the time hyperparathyroidism develops and leads to an increase in bone turnover (high turnover osteodystrophy; HTO) which can lead to demineralisation of the skeleton, bone fractures and calcifications of soft-tissue and blood vessels. HTO can be treated by administration of vitamin D and/or cinacalcet as well as optimized phosphate control and balanced calcium metabolism. In HTO therapy, target levels of phosphate, calcium and PTH should be considered and bone metabolism should be kept in a slight elevated stage in order to prevent low turnover osteodystrophy.     

High-turnover-Osteodystrophie

In chronic kidney disease hyperphosphatemia, vitamin D deficiency and rising fibroblast growth factor (FGF) 23 levels lead to increased parathyroid hormone (PTH) levels. Progressive hyperparathyroidism which has been present for long periods of time leads to an increase in bone turnover (high turnover osteodystrophy, HTO) which in turn leads to demineralization of the skeleton, bone fractures and calcification of soft tissue and blood vessels. A decrease in PTH and treatment of HTO can be achieved by administration of vitamin D and/or cinacalcet as well as optimized phosphate control and balanced calcium metabolism. In HTO therapy, target levels of phosphate, calcium and PTH should be considered and bone metabolism should be maintained at a slightly elevated level in order to prevent low turnover osteodystrophy.     

Bone disease in chronic renal failure and its modern therapy

Renal bone disease is one of the most serious complications of chronic renal failure. Secondary hyperparathyreosis is decisive for its pathogenesis. Current prevention and treatment emphasises pathogenetic and clinical interrelationships between bone tissue involvement and cardiovascular complications (CKD-MBD, bone and venous involvement associated with chronic renal disease). The treatment should first correct hyperphosphatemia and, subsequently, hyperreactivity of parathyroid glands through vitamin D receptor (VDR) and calcium receptor (CaR) modulation. Three groups of drugs play a fundamental role here (GIT phosphate binders, calcimimetics and vitamin D receptor activators). Certain other therapeutic approaches are used in some specific situations such as, among others, refractory hyperparathyreosis or calciphylaxis.     

Phosphatbinder, Vitamin D, Cinacalcet

In the future, clinical treatment recommendations with regard to chronic kidney disease mineral and bone disorder (CKD-MBD) will have to consider cardiovascular as well as bone manifestations of secondary hyperparathyroidism and dysregulation of calcium and phosphate homeostasis. Differential therapy, including phosphate binders, active vitamin D analogues, and calcimimetics, must be tailored to the individual patient. Comorbidities, risk profiles, and also health-economic aspects will be important for guiding decision making.