继发性甲状旁腺功能亢进的治疗

慢性肾脏疾病（CKD）并发的继发性甲状旁腺功能亢进（SHPT）是矿物质代谢紊乱的直接原因,后者与CKD患者的高死亡率直接相关。大量证据表明,SHPT对终末期。肾脏疾病（ESRD）患者心血管疾病的病理生理进程起着非常重要的作用。本文简要介绍SHPT的临床治疗及其进展。     

继发性甲状旁腺功能亢进的临床表现

继发性甲状旁腺功能亢进（SHPT）是慢性肾脏病（CKD）的常见并发症,SHPT在CKD早期即已开始,并随着肾功能的恶化进行性加重。低钙、高磷和活性维生素D3合成障碍不仅是SHPT的主要表现,也参与SHPT的发生与发展。SHPT患者甲状旁腺素（PTH）等毒素对机体的影响,可能与尿毒症患者骨骼系统、心血管系统、血液系统、皮肤病变、神经肌肉系统并发症有关。     

慢性肾脏病继发性甲状旁腺功能亢进的研究进展

正继发性甲状旁腺功能亢进(secondary hyperparathyroidism,SHPT)是慢性肾脏病(chronic kidney disease,CKD)患者最常见的并发症之一,它属于慢性肾脏病-矿物质和骨异常(chronic kidney disease-mineral and bone disorder,CKD-MBD)的一种重要表现类型。随着CKD患者生存期延长,SHPT的高发病率     

继发性甲状旁腺功能亢进症外科治疗现状

继发性甲状旁腺功能亢进症(SHPT)是终末期慢性肾脏病(CKD)最为常见的并发症,通常表现为骨关节疼痛、骨骼畸形、四肢麻木乏力等一系列症状,严重影响患者的生存质量。有效的治疗干预对降低SHPT患者的病死率和发病率是非常重要的。多数早期患者应用药物结合充分透析的方式进行控制是非常有效的,但随着病情的进展,SHPT会进入不...     

外科手术在继发性甲状旁腺功能亢进症中的地位

<正>近年来，慢性肾脏病(chronic kidney disease, CKD)已成为影响我国公共卫生健康的重大问题之一。目前，我国CKD的患病率约为10.8%(11.7%～15.1%)[1-2]。继发性甲状旁腺功能亢进(secondary hyperparathyroidism, SHPT)是CKD 最常见的并发症之一，SHPT病人钙磷代谢紊乱刺激甲状旁腺过度分泌甲状旁腺激素(parathyroid hormone, PTH),     

继发性甲状旁腺功能亢进症的治疗进展

CKD早期就会出现钙、磷、维生素D和PTH代谢失衡,并引起继发性甲状旁腺功能亢进症(SHPT),随着肾功能下降,SHPT也愈加明显。SHPT的治疗相当棘手,标准的治疗方法包括补钙、限制磷摄入、磷结合剂及维生素D制剂的应用。但这些治疗通常会影响血钙、磷浓度,从而加重疾病并增加骨骼外并发症的发病率和死亡率。本文就SHPT的治疗方面作一综述。     

慢性肾衰竭继发性甲状旁腺功能亢进发病机制及治疗进展

继发性甲状旁腺功能亢进(secondary hyperparathyroidism,SHPT)是慢性肾衰竭常见的严重并发症之一,在其发病机制的研究中,PTH信号通路及FGF-23调节矿物质代谢的重要作用都是当今研究的热点.慢性肾脏病(chronic kidney disease,CKD)患者SHPT的治疗进展,包括磷结合剂、活性维生素D及钙敏感受体激动剂的应用都取得了新的突破.超声引导下甲状旁腺无水乙醇注射和外科手术是目前治疗SHPT的有效方法.     

降浊解毒胶囊对慢性肾病非透析患者继发性甲状旁腺功能亢进症的影响

正慢性肾病(CKD)早期即可出现继发性甲状旁腺功能亢进症(SHPT),晚期SHPT表现损伤全身血管、骨骼等各系统,引起肾性骨营养不良、血管和心瓣膜钙化,心血管结构和功能改变,增加心血管死亡率[1]。因此在CKD早中期即给予骨化三醇常规治疗,晚期如SHPT严重则予骨化三醇冲击治疗,疗效显著。但骨化三醇价格较昂贵,有潜在的毒性和高钙的副作用,故开发疗效好、副作用小的中药制剂是很有必要的。我们自2013年     

慢性肾脏病患者甲状旁腺切除术后低钙血症的处理

继发性甲状旁腺功能亢进（secondary hyperparathyroidism,SHPT）是慢性肾脏病（chronic kidney disease,CKD）发展至中晚期常见的一种严重影响患者生活质量的并发症,发病机制主要是CKD进展导致肾脏产生的1,25（OH）2D3分泌不足,导致低钙、高磷刺激甲状旁腺增生,导致血甲状旁腺激素（parathyroid hormone,PTH）增高,SHPT患者不仅表现为钙磷代谢紊乱、转移性钙化,还会导致骨骼、关节疼痛、骨骼畸形（如退缩人综合征）。     

甲状旁腺切除术对慢性肾脏病5期伴严重继发性甲状旁腺功能亢进患者心率昼夜节律的影响

目的:观察慢性肾脏病（chronic kidney disease,CKD）5期患者心率昼夜节律的变化,分析甲状旁腺切除术（parathyroidectomy,PTX）对伴严重继发性甲状旁腺功能亢进（secondary hyperparathyroidism,SHPT）患者心率节律的影响。方法:横断面观察213例CKD...     

Pin1 and secondary hyperparathyroidism of chronic kidney disease: gene polymorphisms and protein levels

Background: Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (Pin1) is a key regulator of PTH mRNA stability. Secondary hyperparathyroidism (SHPT), which is characterized by elevated serum PTH levels, is a common complication of CKD. We investigated the possible associations between CKD with SHPT (CKD SHPT) and single-nucleotide polymorphisms of the Pin1 gene and compared the levels of the Pin1 protein in the CKD SHPT patients with those of the controls.

Methods: The study group included 251 CKD SHPT patients and 61 controls. One putative functional SNP (single nucleotide polymorphism) in the Pin1 promoter (rs2233679C?>?T: c.?667C?>?T) is the main object. Genotyping was performed on purified DNA using polymerase chain reaction-restriction (PCR) and restriction fragment length polymorphisms (RFLP). The levels of Pin1 were measured in serum using an enzyme-linked immunosorbent assay.

Results: Genotyping showed that CT?+?TT in the Pin1 promoter was significantly more common in the CKD SHPT group than in the control group (p<.05). The correlation analysis demonstrated that a significant difference in the C to T transition in the Pin1 promoter contributed to CKD SHPT (χ²=12.47, p<.05; Odds ratios (OR)?=?1.26, 95% confidence (CI) intervals =1.06–1.49). The multivariate logistic regression analysis reported that the OR and 95%CI were 12.693 and 2.029–75.819 (p<.05), respectively, in the Pin1 gene promoter ?667T variant genotypes (CT?+?TT) after adjusting for other factors, and those values in Pin1 were 0.310 and 0.122–0.792 (p<.05).

Conclusion: The ?667T genetic variants in the Pin1 promoter contribute to an increased risk of CKD SHPT and may be biomarkers of susceptibility to CKD SHPT.     

Diseases of the parathyroid gland in chronic kidney disease

During the past few years, remarkable advances have been made in the understanding and the management of parathyroid diseases in patients with chronic kidney disease (CKD). One of the important insights is the identification of fibroblastic growth factor 23, which has greatly reshaped our understanding of secondary hyperparathyroidism (SHPT). The recent introduction of calcimimetic cinacalcet hydrochloride has led to a major breakthrough in the management of SHPT. Recognition of circulating molecular forms of parathyroid hormone (PTH) is also a major milestone in the accurate assessment of parathyroid function in CKD. Primary hyperparathyroidism should also be considered in patients with CKD, because it can cause various renal manifestations and can also occur as a sporadic disease in these patients. Hypoparathyroidism is occasionally seen in dialysis patients in the setting of diabetes mellitus and malnutrition–inflammation complex syndrome, as well as after parathyroidectomy for advanced SHPT. For patients with adynamic bone disease due to hypoparathyroidism and/or skeletal resistance to PTH, teriparatide, a PTH analog, may have potential for improving bone metabolism and reducing the risk of fracture. In this review, we summarize our current knowledge on diseases of the parathyroid gland in CKD patients, with a particular focus on recent work in the field.     

Calcimimetics in chronic kidney disease: evidence, opportunities and challenges

Secondary hyperparathyroidism (SHPT) remains a highly prevalent and important complication in patients with chronic kidney disease (CKD). Indeed, SHPT may compromise bone health and contribute to the increased cardiovascular risks of these patients. Calcimimetic agents may help to control SHPT and to achieve the stringent mineral metabolism targets in patients with CKD stage 5D. Whether this will translate in improved patient-level outcomes remains to be demonstrated in adequately powered prospective intervention studies. These studies are currently ongoing. Additional investigations are required to define how calcimimetics fit best in the expanding armamentarium to treat SHPT. The role of vitamin D (analogs) and parathyroidectomy needs to be reevaluated in the calcimimetic era. Persistent hyperparathyroidism after successful renal transplantation may also become an important indication for therapy with calcimimetics. In patients with this complication, calcimimetics may help to improve bone health both by suppressing bone turnover and demineralization and may retard or prevent nephrocalcinosis of the graft. The evidence for using calcimimetics in CKD patients not yet on dialysis, conversely, is less straightforward. In these patients, therapy for SHPT should rather be focused on the primary trigger, i.e. the high phosphate load relative to the functional nephron mass.     

New therapies for uremic secondary hyperparathyroidism.

Secondary hyperparathyroidism (SHPT) is a common and serious complication of chronic kidney disease (CKD). It affects more than 300,000 end-stage renal disease patients treated by dialysis and probably more than 3 million patients with CKD worldwide. For a long time, traditional therapies for SHPT had consisted of correcting the hypocalcemia using calcium salts and vitamin D derivatives, preventing the hyperphosphatemia by calcium- or aluminum-containing intestinal phosphate binders, and recently by using no metal-containing intestinal phosphate binders; however, these therapies are limited by the occurrence of hypercalcemia, hyperphosphatemia, and the lack of specificity and long-term efficacy. Moreover, surgical parathyroidectomy (PTX), which remains the gold standard therapy, is not exempt from risk. PTX exposes patients to anesthesia risks, presurgical and postsurgical complications, and in many cases a permanent state of hypoparathyroidism. Thus, the medical treatment of SHPT became an ideal target for the development of new therapies and strategies. The purpose of this article is to provide an overview of these new therapies, including vitamin D analogs, intestinal phosphate binders, calcimimetics, parathyroidectomies, tyrosine kinase inhibitors, azydothymidine, anticalcineurins, N-terminal truncated parathyroid hormone fragments, bisphosphonates, calcitonin, osteoprotegerin, and others. The use of these new therapies alone or in combination may help to optimize the future treatment of SHPT in CKD patients.     

Calcimimetics or vitamin D analogs for suppressing parathyroid hormone in end-stage renal disease: time for a paradigm shift?

Considerable advances have been made in the understanding of the pathogenesis and treatment of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD). These include the discovery that the calcium-sensing receptor has an important role in the regulation of parathyroid gland function, the development of calcimimetics to target this receptor, the recognition that vitamin D receptor activation has important functions beyond the regulation of mineral metabolism, the identification of the phosphaturic factor fibroblast growth factor 23 and the contribution of this hormone to disordered phosphate and vitamin D metabolism in CKD. However, despite the availability of calcimimetics, phosphate binders, and vitamin D analogs, control of SHPT remains suboptimal in many patients with advanced kidney disease. In this Review, we explore several unresolved issues regarding the pathogenesis and treatment of SHPT. Specifically, we examine the significance of elevated circulating fibroblast growth factor 23 levels in CKD, question the proposition that calcitriol deficiency is truly a pathological state, explore the relative importance of the vitamin D receptor and the calcium-sensing receptor in parathyroid gland function and evaluate the evidence to support the treatment of SHPT with calcimimetics and vitamin D analogs. Finally, we propose a novel treatment framework in which calcimimetics are the primary therapy for suppressing parathyroid hormone production in patients with end-stage renal disease.     

Effects of parathyroidectomy on plasma iPTH, (1-84)PTH and (7-84)PTH levels in patients with stage 5 chronic kidney disease

Objective Currently, parathyroid hormone (PTH) is mainly measured by the second generation intact PTH (iPTH) assay which detects both full-length (1-84)PTH and (7-84)PTH fragments. The third generation whole PTH (wPTH) assay however has turned out to be specific for (1-84)PTH. The aim of this study is to investigate the features of plasma iPTH, (1-84)PTH, (7-84)PTH levels in patients with stage 5 chronic kidney disease (CKD), and evaluate the effects of parathyroidectomy (PTX) on above markers in severe secondary hyperparathyroidism (SHPT) patients. Methods A cross-sectional study including 90 controls and 233 stage 5 CKD patients, and a prospective follow-up study in 31 severe SHPT patients were conducted. Plasma iPTH and (1-84)PTH levels were measured by the second and third generation assay, respectively. Circulating (7-84)PTH level was calculated by subtracting the (1-84)PTH value from the iPTH value. Results Plasma levels of iPTH, (1-84)PTH, (7-84)PTH were higher (P＜0.01), and (1-84)PTH/iPTH was lower (P＜0.01) in stage 5 CKD patients than in controls. For severe SHPT patients with PTX (n=74), plasma iPTH, (1-84)PTH and (7-84)PTH concentrations were significantly increased compared to non-PTX group (n=159) (P＜0.01), and the increase of (7-84)PTH level was more striking than (1-84)PTH. Meanwhile, the value of (1-84)PTH/iPTH was decreased (P＜0.01). Plasma iPTH level was strongly correlated with (1-84)PTH level (r=0.980, P＜0.01) in stage 5 CKD patients. Also, both iPTH and (1-84)PTH levels were positively correlated with serum alkaline phosphatase, dialysis vintage and serum phosphorus (P＜0.01). After PTX (median interval of follow-up: 7.1 months), plasma iPTH, (1-84)PTH, (7-84)PTH concentrations were decreased (by 92.9%, 89.7%, 95.8%, P＜0.01, respectively) greatly and (1-84)PTH/iPTH was increased (P＜0.01). Conclusions In stage 5 CKD patients, plasma iPTH, (1-84)PTH, (7-84)PTH levels are greatly increased while (1-84)PTH/iPTH is decreased, and PTX can significantly improve abnormality of above markers in severe SHPT patients. The second generation PTH assay overestimates the severity of SHPT, and the accurate measurement of (1-84)PTH by the third assays is more conducive to diagnosis and treatment of CKD and SHPT patients.     

Effects of hyperparathyroidism patients’ serum and klotho protein on the apoptosis of human umbilical vein endothelial cells

Objective To investigate the effects and underlying mechanism of secondary hyperparathyroidism (SHPT) patients’serum and klotho protein on the apoptosis of human umbilical vein endothelial cells (HUVECs). Methods Three types of mixed serum from 15 patients with SHPT (serum S), 10 CKD stage 5 patients without SHPT (serum C) and 15 healthy volunteers (serum H) were collected. HUVECs were incubated with 10% serum H,10% serum C, 10% serum S and 10% serum S plus klotho respectively. The apoptosis rate of endothelial cells was evaluated by flow cytometry. The activity of Caspase-3 was measured by spectrophotometry. The levels of AKT and phosphorylated forms of AKT (p- AKT) were detected by Western blotting (with or without PI3K/AKT inhibitor LY294002). Results The apoptosis of HUVECs was both induced by the serum S and serum C. The apoptosis rate was greater in serum S group than that in serum C group (P＜0.05). The apoptosis was partly inhibited when klotho protein (50-100 μg/L) was added (P＜0.05), accompanying the up-regulation of p-AKT. The above effects could be blocked by LY294002. The activity of Caspase-3 was up-regulated in SHPT group compared to healthy control group (P＜0.05) and the up-regulation could also be inhibited by klotho protein (P＜0.05). Conclusions The apoptosis of HUVECs is induced by the serum from CKD stage 5 patients without SHPT and SHPT patients. Klotho protein can protect the HUVECs from apoptosis by up-regulating p-AKT and inhibiting Caspase-3.     

Research on kidney and mineral metabolism in Japan: past,present, and future

Since the identification of the kidney was the main site for the synthesis of calcitriol (1α, 25-dihydroxycholecalciferol), research on chronic kidney disease (CKD)-associated mineral metabolism disorders and their management has made rapid progress. Various active analogues of calcitriol have clinically become available for treating secondary hyperparathyroidism (SHPT), which is a representative mineral metabolism abnormality in CKD patients. A calcimimetic compound cinacalcet hydrochloride has also been developed for the medical management of SHPT through a different mechanism involving the calcium-sensing receptor. The concept of CKD-mineral and bone disorder (CKD-MBD) was proposed in 2006 to provide a comprehensive understanding of a disorder related to mineral metabolism abnormalities of CKD, based on the fact that these abnormalities are closely associated with cardiovascular disease as well as bone disorders (renal osteodystrophy). There has been a recent surge in the development of phosphate binders for CKD-MBD, focused on an effort to improve mortality. In Japan, high-quality basic and clinical research on CKD-MBD has led to the development of novel therapeutic drugs, such as maxacalcitol, falecalcitriol, and bixalomer. New practice guidelines have been published and are widely adapted in clinical practice.     

The Receptor Activator of Nuclear Factor-κB Ligand Inhibitor Osteoprotegerin Is a Bone-Protective Agent in a Rat Model of Chronic Renal Insufficiency and Hyperparathyroidism

Osteoprotegerin (OPG) acts by neutralizing the receptor activator of nuclear factor-κB ligand (RANKL), the primary mediator of osteoclast differentiation, function, and survival. We examined whether OPG could affect the bone loss associated with chronic kidney disease (CKD) in a rodent model of CKD and secondary hyperparathyroidism (SHPT). SHPT was induced in rats by 5/6 nephrectomy (5/6 Nx) and a 1.2% P/0.6% Ca²⁺ diet. Starting 1 week after 5/6 Nx, rats were treated with vehicle (veh) or OPG-Fc (3 mg/kg, intravenously) every 2 weeks for 9 weeks. At baseline, 3, 6, and 9 weeks, blood was taken and bone mineral density (BMD) and bone mineral content (BMC) were assessed by dual-energy X-ray absorptiometry. Serum parathyroid hormone (sPTH) levels reached 912 pg/ml in 5/6 Nx rats vs. 97 pg/ml in shams at 9 weeks. OPG-Fc had no effect on sPTH or Ca²⁺ levels throughout the 9-week study, indicating that SHPT was a renal effect independent of bone changes. At 3 weeks, 5/6 Nx-veh rats had osteopenia compared with sham-veh rats and 5/6 Nx-OPG-Fc rats had significantly higher percent changes in whole-body BMC, leg BMD, and lumbar BMD versus 5/6 Nx-veh rats. By 6–9 weeks, elevated sPTH was associated with reversal of bone loss and osteitis fibrosa in the proximal tibial metaphysis. OPG-Fc decreased this sPTH-driven high bone turnover, resulting in augmented thickness of proximal tibial trabeculae in 5/6 Nx rats. Thus, RANKL inhibition with OPG-Fc can block the deleterious effects of continuously elevated sPTH on bone, suggesting that RANKL may be an important therapeutic target for protecting bone in patients with CKD and SHPT.