Article: Metabolic Basis and Pathogenesis of Skeletal Muscle Dysfunction as Cause of Frailty in Chronic Kidney Disease
Patients with chronic kidney disease (CKD) possess an increased risk of developing physical or phenotypic frailty. The skeletal muscle dysfunction underpinning physical frailty has been associated with increased mortality. CKD-related phenotypic frailty shares features with ageing-related frailty, and CKD has thus been touted as a clinically relevant model of premature ageing.
The aim of this review was to examine the metabolic basis and pathogenesis of the skeletal muscle dysfunction responsible for phenotypic frailty in patients with CKD.
Patients with CKD possess a high prevalence of physical frailty compared to those with other chronic diseases. In dialysis- and non-dialysis-dependent CKD patients, frailty reduces overall physical function and induces gait abnormalities, i.e., decline in gait speed. The latter is a strong predictor of mortality in dialysis-dependent CKD patients.
Frailty is the clinical manifestation of multiple organ system functional impairment, which is central to CKD. While the frailty phenotype is extremely broad, it encompasses skeletal muscle dysfunction, known as sarcopenia. Sarcopenia’s prevalence increases in patients with CKD compared to aged patients without it and worsens as CKD progresses.
Furthermore, in aged patients and in those with CKD, sarcopenia possesses a metabolic basis. Both ageing and CKD are accompanied by the deterioration of key repair processes, including reductions in mitochondrial autophagy. Skeletal muscle dysfunction in ageing and CKD patients is also associated with endocrine abnormalities (i.e., insulin resistance), mitochondrial dysfunction, oxidative stress, metabolic acidosis, and increased inflammation. As such, correcting these characteristics’ metabolic disturbances may reduce phenotypic frailty. Future research should aim to identify metabolic disturbances improved by dialysis capable of reducing sarcopenia, and thus, frailty. Identification of such disturbances may lead to the development of non-dialysis, conservative management strategies, and their implementation in clinical practice may lead to the treatment and prevention of frailty in CKD patients.
Reviewed by: S. Duarte
Authors: Wesson DE, Mathur V, and Tangri N
Published in: American Journal of Nephrology 2022