Muscle Wasting in Chronic Kidney Disease: Mechanism and Clinical Implications-A Narrative Review

Abstract

Muscle wasting, known to develop in patients with chronic kidney disease (CKD), is a deleterious consequence of numerous complications associated with deteriorated renal function. Muscle wasting in CKD mainly involves dysregulated muscle protein metabolism and impaired muscle cell regeneration. In this narrative review, we discuss the cardinal role of the insulin-like growth factor 1 and myostatin signaling pathways, which have been extensively investigated using animal and human studies, as well as the emerging concepts in microRNA- and gut microbiota-mediated regulation of muscle mass and myogenesis. To ameliorate muscle loss, therapeutic strategies, including nutritional support, exercise programs, pharmacological interventions, and physical modalities, are being increasingly developed based on advances in understanding its underlying pathophysiology.

Keywords: chronic kidney disease; exercise; molecular mechanism; muscle regeneration; muscle wasting; nutrition; pharmaceutical intervention; physical modality; protein metabolism.

Figure 1

Illustration of the relationship between CKD-related factors and muscle wasting. Upward arrows indicate increase or activation; downward arrows indicate decrease or suppression. The graphics used in this figure are adapted from Sevier Medical Art (www.smart.servier.com, accessed on 5 April 2022).

Figure 2

Altered cellular signaling pathways underlying muscle wasting in CKD. (Blue lines/arrows indicate activation; red lines/arrows indicate inactivation; upward arrows indicate upregulation or increase; downward arrows indicate downregulation or decrease.) The graphics used in this figure are adapted from Sevier Medical Art (www.smart.servier.com, accessed on 5 April 2022).