The causes of excess cardiovascular mortality associated with chronic kidney disease (CKD) have been attributed in part to the CKD-mineral bone disorder syndrome (CKD-MBD), wherein, novel cardiovascular risk factors have been identified. New advances in the causes of the CKD-MBD are discussed in this review. They demonstrate that repair and disease processes in the kidneys release factors to the circulation that cause the systemic complications of CKD. The discovery of WNT inhibitors, especially Dickkopf 1 (Dkk1), produced during renal repair as participating in the pathogenesis of the vascular and skeletal components of the CKD-MBD implied that additional pathogenic factors are critical. This lead to the discovery that activin A is a second renal repair factor circulating in increased levels during CKD. Activin A derives from peritubular myofibroblasts of diseased kidneys, wherein it stimulates fibrosis, and decreases tubular klotho expression. Activin A binds to the type 2 activin A receptor, ActRIIA, which is variably affected by CKD in the vasculature. In diabetic/atherosclerotic aortas, specifically in vascular smooth muscle cells (VSMC), ActRIIA signaling is inhibited and contributes to CKD induced VSMC dedifferentiation, osteogenic transition and neointimal atherosclerotic calcification. In nondiabetic/nonatherosclerotic aortas, CKD increases VSMC ActRIIA signaling, and vascular fibroblast signaling causing the latter to undergo osteogenic transition and stimulate vascular calcification. In both vascular situations, a ligand trap for ActRIIA prevented vascular calcification. In the skeleton, activin A is responsible for CKD stimulation of osteoclastogenesis and bone remodeling increasing bone turnover. These studies demonstrate that circulating renal repair and injury factors are causal of the CKD-MBD and CKD associated cardiovascular disease.

Keith A. Hruska

Toshifumi Sugatani

Olga Agapova

Yifu Fang

Bone

BONE 是一个跨学科论坛，用于快速发表有关骨和矿物质代谢的基础、转化和临床方面的原创文章和评论。该杂志还鼓励提交有关骨骼与其他器官系统相互作用的论文，包括软骨、内分泌、肌肉、脂肪、神经、血管、胃肠道、造血和免疫系统。特别注意将实验研究应用于临床实践。

BONE is an interdisciplinary forum dedicated to the rapid publication of original articles and reviews concerning the fundamental, translational, and clinical aspects of bone and mineral metabolism. The journal also encourages submissions on the interactions between bone and other organ systems, including cartilage, endocrine, muscle, fat, nerve, vascular, gastrointestinal, hematopoietic, and immune systems. Special emphasis is placed on applying experimental research to clinical practice.

BONE 是一个跨学科的论坛，旨在快速发表关于骨骼和矿物质代谢的基础研究、转化研究和临床研究的原创文章和评论。该杂志还鼓励提交关于骨骼与其他器官系统相互作用的论文，包括软骨、内分泌、肌肉、脂肪、神经、血管、胃肠道、造血和免疫系统。特别关注将实验研究应用于临床实践。

The chronic kidney disease — Mineral bone disorder (CKD-MBD): Advances in pathophysiology

It is demonstrated that circulating renal repair and injury factors are causal of the CKD-MBD and CKD associated cardiovascular disease.

Category	Quartile
医学	2
医学, 内分泌学与代谢	2

The chronic kidney disease — Mineral bone disorder (CKD-MBD): Advances in pathophysiology

ivySCI AI Smartly Parses PDF, Answers Researchers' Questions, and Helps You Understand Papers in Seconds

Journal Info

Category	Quartile
ENDOCRINOLOGY & METABOLISM	2