Skeletal Muscle and Kidney Crosstalk in Chronic Kidney Disease

Abstract

The functioning of complex organisms requires a constant and delicate balance of processes both between and within cells, tissues, and organ systems. There is growing appreciation for the role of signalling crosstalk connecting different organ systems of the body, even from tissues traditionally classified as "inert" in terms of their capacity to produce chemical signals that can act on other organ systems. Many of these secreted molecules have been shown to contribute to, or exacerbate, a variety of functions and diseases in other organ systems, even if the two organs are not functionally linked. For example, there is a strong association with skeletal muscle atrophy and dysfunction in patients with chronic kidney disease (CKD). Identification of molecules produced and secreted by skeletal muscle has existed for some time, and there is emerging evidence that skeletal muscle may directly affect kidney function. Conversely, factors produced and secreted by the kidneys in various models of CKD have been shown to contribute to reduced muscle functionality. This review will focus on crosstalk in both directions between skeletal muscle and the kidneys. The emphasis will be on direct interaction between these organs using examples of secreted factors that are produced by the muscle or kidneys (including activin A, myostatin, microRNA's, irisin and mitsugumin 53), often under pathophysiological conditions. Our understanding of how the kidneys and skeletal muscle interact with each other is key to elucidating the pathophysiology processes that drive health and disease.

MG53: A potential therapeutic target for kidney disease

“… 48 Therefore, inhibition of muscle atrophy may prevent CKD progression. 53 Studies have shown that the genetic knockout of MG53 in mice results in muscle dystrophy, along with decreased kidney function. 10 , 17 , 23 Moreover, rhMG53 was demonstrated to relieve muscle fibrosis and affect histological structures in a mouse model of muscular dystrophy.…”

Chronic Kidney Disease in Patients with Hip Fracture: Prevalence and Outcomes

“…Although kidney-related mechanisms involved in maintenance of musculoskeletal health [14,[17][18][19][20][21] have been intensively researched for decades and the association between CKD and osteoporotic fractures (OF) is well established [22,23], studies on CKD combined with HF, the most devastating complication of osteoporosis (OP), are relatively rare [13,24,25]. Te relationship between kidney function and postoperative outcomes in hip fracture (HF) patients has not been systematically investigated, and the few studies that evaluated the input of CKD on HF outcomes have yielded conficting results [25][26][27][28][29].…”