Dr LIMY WONG1,2, Ms RACHEL KENNY2, Ms JENNIFER HOWARD1, Professor LAWRENCE P. MCMAHON1,2
1Department of Renal Medicine, Eastern Health, Box Hill, Australia, 2Department of Renal Medicine, Monash University Eastern Health Clinical School, Box Hil, Australia
Aim: The aim of this systematic review is to summarise the current evidence on molecular changes in the skeletal muscle of humans and rodents with chronic kidney disease (CKD) and to assess the strength of such evidence.
Background: Loss of skeletal muscle mass is prevalent among CKD patients and is associated with significant morbidity and mortality. The underlying molecular pathogenesis has yet to be fully elucidated.
Methods: The PubMed and EMBASE databases were searched using three main themes: messenger ribonucleic acid/protein/microRNA expression, skeletal muscle and CKD. This study was conducted in accordance with the PRISMA standards.
Results: Ninety-eight studies were included in the systematic review, comprising 26 prospective human clinical studies, 4 human and rodent studies, and 68 rodent-only studies (32 mouse and 36 rat). The sample sizes of human studies were predominantly small (73% of studies had ≤40 participants). Qualitative polymerase chain reaction (qPCR) was the most commonly used method for gene expression. None of the studies fulfilled the Minimum Information for Publication of qPCR Experiments (MIQE) criteria for quality of gene analysis. Most studies investigated only a few genes or a specific signalling pathway. The identified differentially expressed genes and proteins belonged to eight major pathways, including apoptosis, autophagy, inflammation, insulin/insulin-like growth factor 1 signalling, lipid metabolism, mitochondrial function, muscle cell growth and differentiation, and protein degradation, similar to other chronic disease states.
Conclusions: The current evidence regarding molecular alterations in the skeletal muscle in CKD is largely derived from small, heterogeneous studies. Nevertheless, markedly similar modifications in the major biological pathways between CKD and other chronic diseases supports shared deleterious molecular mechanisms producing muscle atrophy, irrespective of the underlying chronic disease.
Biography:
Limy Wong is a Nephrologist and Postdoctoral Fellow at Eastern Health. She graduated with First Class Honours in Medicine from the Royal College of Surgeons in Ireland and completed Nephrology specialist training in Ireland and the UK, gaining the Specialty Certificate in Nephrology from the Royal College of Physicians. She completed a Wellcome Trust Clinical PhD Fellowship at the University of Cambridge, studying the genetics of ANCA-associated vasculitis. She was recently awarded the 2021 and 2022 RACP Jacquot Research Establishment Fellowship, to conduct basic science and translational research to answer the questions surrounding the pathogenesis of sarcopenia in CKD patients.