Pharmacotherapy of end-stage renal disease

Importance of the field: The incidence and prevalence of end-stage renal disease (ESRD) requiring renal replacement therapy (RRT) continues to grow worldwide. ESRD causes significant morbidity and mortality and has enormous financial and personal costs.

Areas covered in this review: Major electronic databases (including the Cochrane Library, MEDLINE and EMBASE) were searched from 1989 to September 2009 to summarize current pharmacotherapy of ESRD-associated complications in adults receiving maintenance dialysis (hemodialysis or continuous ambulatory peritoneal dialysis). Current guidelines for the treatment of ESRD (e.g., NKF-K/DOQI, KDIGO, and the ERA-EDTA's European Renal Best Practice Guidelines) were included.

What the reader will gain: Commonly used pharmacological treatment strategies for chronic arterial hypertension, anemia, iron management, dyslipidemia, hyperglycemia, and for disturbances of bone and mineral metabolism, including hyperphosphatemia and secondary hyperparathyroidism in ESRD, are presented. In addition, the reader will learn that nonadherence to oral medication in ESRD can contribute significantly to excess morbidity and mortality of the dialysis population.

Take home message: Improvements in pharmacotherapy of ESRD may be at least in part counteracted by continuously increasing age and comorbid disease of the dialysis population. Individualized and tailor-made pharmacological management of the ESRD patient remains a challenge for the future.     

Does a rise in plasma erythropoietin after high-altitude exposure affect FGF23 in healthy volunteers on a normal or low-phosphorus diet?

Background and aimsData of experimental rodent models suggest that hypoxia with subsequent increase in erythropoietin stimulates the expression of the phosphaturic hormone fibroblast growth factor 23 (FGF23).Methods and resultsTo translate the findings of animal studies into human physiology, herein we exposed eight healthy volunteers to high altitude (2656 m above sea level) for four days. The volunteers were randomized on a low-phosphorous diet (n = 4) or a normal phosphorus diet (n = 4). Although high-altitude exposure caused a significant increase in plasma erythropoietin (EPO) (before high-altitude exposure: low phosphorus: median EPO 6.6 mIU/ml [interquartile range (IQR) 6.0; 8.2], normal phosphorus: median EPO 9.0 mIU/ml [IQR 7.9; 11.5]; at day 2: low phosphorus: median EPO 21.3 mIU/ml [IQR 19.5; 23.8], normal phosphorus: median EPO 19.4 mIU/ml [IQR 18.0; 20.8]), there was no consistent increase in plasma c-terminal FGF23 or plasma intact FGF23. We observed only a single, intermittent peak in c-terminal FGF23 levels after 5 h of maximal aerobic exercise.ConclusionThese data do not support a substantial effect of moderate hypoxia alone on the expression of FGF23, but they suggest that combined exercise and high-altitude exposure may temporarily induce FGF23 expression.     

Adynamic bone disease: Revisited

The bone and mineral disorders form an integral part of the management of a chronic kidney disease (CKD) patient. Amongst various types of bone pathologies in chronic kidney disease-mineral bone disorder (CKD-MBD), the prevalence of adynamic bone disease (ABD) is increasing. The present review discusses the updated pathophysiology, risk factors, and management of this disorder.     

慢性肾脏病矿物质和骨代谢紊乱血清生化学指标变化的临床分析

目的综合分析骨代谢的状态,指导临床上慢性肾脏病矿物质及骨代谢紊乱(CKD-MBD)的诊断、分型及治疗。方法对2008年11月至2009年2月在中国医科大学附属第一医院肾内科住院的56例CKD4期、5期及长期血液透析(5年以上)三组不同分期的慢性肾功不全患者清晨空腹抽血化验血清钙、磷、iPTH、bAP、TRACP,并行骨密度检查。结果三组不同分期慢性肾功不全患者CKD-MBD的发生率分别为36.4%、73.0%、87.5%(χ2=6.861,P0.05),其中高转运性骨病占65.79%,低转运性骨病占34.21%。高转运性骨病患者血清bAP和TRACP活性明显升高,而低转运性骨病患者血清bAP和TRACP活性降低。结论CKD-MBD是慢性肾功不全患者常见的并发症,以高转运性骨病为主,但低转运性骨病不容忽视。bAP和TRACP是反映成骨细胞和破骨细胞活性的敏感指标,临床上可作为鉴别高、低转运性骨病的可靠依据,结合血清钙、磷、iPTH、骨密度的改变,可以综合分析骨代谢状态,指导CKD-MBD的诊断、分型、药物的选择和综合治疗。     

维生素K对CKD-MBD骨代谢异常以及血管钙化的治疗及作用机制

慢性肾脏疾病矿物质和骨异常(chronic kidney disease mineral and bone disorder ,CKD-MBD)是慢性肾脏病（chronic kidney disease,CKD）的主要并发症之一,是一种全身性的矿物质和骨代谢障碍,包括钙、磷、甲状旁腺素（PTH）或维生素D代谢异常,骨转换、矿化、骨量、骨的线性生长或强度异常以及血管或其他软组织钙化,增加了CKD患者的心血管风险、骨折风险以及死亡率[1]。临床治疗上以控制钙磷平衡、降低甲状旁腺素、抑制血管钙化为主,包括使用含钙/非含钙磷结合剂、活性维生素D及其类似物、西那卡塞等。维生素K是一组脂溶性维生素,可作为γ-谷氨酰羧化酶（γ-glutamyl carboxylase ,GGCX）的辅助因子,该酶通过激活维生素K依赖蛋白（vitamin K-dependent proteins,VKDP）参与凝血因子的活化、凋亡,以及抑制血管钙化、调节骨矿化[2]。越来越多的证据表明,CKD患者患有亚临床维生素K缺乏症,补充维生素K尤其是维生素K2,可增加CKD患者骨强度、抑制血管钙化。本文将从维生素K的缺乏和补充对CKD相关矿物质和骨疾病（CKD-MBD）的影响及其作用机制、临床应用等方面进行阐述。     

The CKD-MBD Syndrome: Hysteresis in PTH Involvement and PTH Administration for Its Management

Chronic kidney disease (CKD) disturbs mineral homeostasis, leading to mineral and bone disorders (MBD). CKD-MBD is a significant problem and currently available treatment options have important limitations. Phosphate retention is thought to be the initial cause of CKD-MBD but serum phosphate remains normal until the late stages of CKD, due to elevated levels of the phosphaturic hormone fibroblast growth factor-23 (FGF-23), and parathyroid hormone (PTH). Reduction of 1,25-dihydroxy-vitamin D (1,25[OH]₂D) concentration is the next event in the adaptive response of the homeostatic system. We argue, and provide the rationale, that calcium retention which takes place concurrently with phosphate retention, could be the reason behind the hysteresis in the response of PTH. If indeed this is the case, intermittent administration of PTH in early CKD could prevent the hysteresis, which arguably leads to the development of secondary hyperparathyroidism, and provide the platform for an effective management of CKD-MBD. © 2020 American Society for Bone and Mineral Research (ASBMR).     

The kidney and bone metabolism: Nephrologists' point of view

The kidney plays an important role in the regulatory system for bone and mineral metabolism. In chronic kidney disease (CKD), various abnormalities, recently named CKD-mineral and bone disorder (CKD-MBD), may develop in this system. The optimal management of CKD-MBD should be achieved without increasing the risk of metastatic calcification, including that of blood vessels. Thus, it is quite important to identify severe cases of hyperparathyroidism refractory to medical therapy. The size of the parathyroid glands, serum levels of fibroblast growth factor (FGF)23, and, possibly, the overproduction of a novel form of parathyroid hormone (PTH), serve as useful markers for this purpose. Adynamic bone disease with low buffering capacity for calcium is another major cause of hypercalcemia in dialysis patients. Our recent studies suggest that indoxyl sulfate accumulated in uremic serum is responsible for the suppression of osteoblastic function. In order to maintain the bone quality in patients with CKD, bone changes due to aging, menopause, and malnutrition need to be considered by nephrolgists and non-nephrologists in collaboration. M. Fukagawa is the recipient of the Academic Award 2005 given by the Japanese Society for Bone and Mineral Research.     

Managing End-Stage Renal Disease: An Alphabetized Mnemonic Strategy

End-stage renal disease (ESRD) is a complex condition that requires knowledge and expertise for its effective management. Nurse practitioners continuously strive to provide adequate and safe care based on rigorous research. The objective of this article is to provide a structured and applicable approach to managing ESRD that is up-to-date and evidence based. To achieve this objective, we created an alphabetized mnemonic and synthesized our discussion to address Anemia, Bone health, Cardiovascular issues, vitamin D deficiency, Electrolytes imbalances, Fluid overload, and Gastroesophageal reflux in patients with ESRD.