Unveiling the Impact of Phosphate on Skeletal Muscle Dysfunction in Chronic Kidney Disease

Background: Chronic Kidney Disease (CKD) is characterized by progressive decline in renal function that ultimately culminates in the inability of the kidneys to effectively maintain homeostasis. The kidneys are a key regulator of phosphate, with other organs assisting in regulation including the skeletal system. In CKD, reduced kidney function leads to hyperphosphatemia. While its impact on the skeletal system is moderately studied, its effects on skeletal muscle are less reviewed. In our literature review, we aim to describe the effects of phosphate in the context of patients who have CKD while providing clinical context for this deserving population. We describe the adverse effects of phosphate on skeletal muscle, clinical implications, management strategies for CKD patients, and future research directions focused on managing skeletal muscle dysfunction. The emphasis of understanding the effects of phosphate on skeletal muscle is important as our review provides important context for healthcare providers who treat patients with CKD. Methods: Our methods included a comprehensive review of the current literature regarding chronic kidney disease, phosphate in the context of chronic kidney disease, the effects of phosphate on skeletal muscle in patients with CKD, and the clinical implications regarding phosphate levels in patients with CKD. We conducted our search through PubMed and have acquired forty-one references for our literature review. The years in which our references were published range from the year 1988 to 2024. Results: Upon review of the literature, several key points are present when considering the clinical context of phosphate in patients with CKD. First, we found that abnormal phosphate levels both directly and indirectly affect calcium levels by decreasing release and decreasing general levels of calcium in the body. Following, the literature suggests a proposed avenue of impaired energy metabolism is an increase in extracellular phosphate. This leads to the creation of reactive oxygen species (ROS) via the mitochondria, which leads to endoplasmic reticulum stress. Next, we describe the effect of high phosphate levels on inflammatory markers like TNF-a and IL-6 are activated. In clinical context, high phosphate levels in patients with CKD have been shown to induce muscle cell atrophy through autophagy activation. Increased muscle wasting is associated with high morbidity and mortality in patients with chronic kidney disease (CKD), necessitating the identification of phosphate-related muscle dysfunction. Although treatment options are broad, managing dietary phosphate intake remains one of the most important preventive options. Other treatments, like Niacinamide, could provide a new means to lower phosphate in CKD patients. Conclusion: We conclude that Further exploration of methods to reduce phosphate levels in CKD patients could improve their outcomes and quality of life. Preventive treatment remains key for CKD patients, as it can reduce phosphate levels through habituation rather than medication. The need for further patient education on the effects of high phosphate consumption in patients with CKD is certainly warranted as this can directly improve the negative effects of skeletal muscle atrophy.