Muscle Atrophy in CKD: A Historical Perspective of Advancements in Its Understanding

This perspective reviews the seminal clinical and experimental observations that led to today's current mechanistic model of muscle protein loss (wasting) in patients with chronic kidney disease (CKD).

Early International Society of Renal Nutrition and Metabolism (ISRNM) meetings facilitated discussions and hypotheses about the causes of muscle wasting in CKD. It became widely recognized that wasting is common and correlated with increased risks of mortality and morbidity. Although anorexia and dietary restrictions contribute to muscle loss, several features of CKD-associated wasting cannot be explained by malnutrition alone. The protein catabolism-inducing actions of metabolic acidosis, inflammation, insulin resistance, endocrine disorders and uremic toxins were progressively identified. Continued research to understand the interactions of inflammation, anabolic resistance, mitochondrial dysfunction, exercise, and nutrition on muscle protein turnover in patients with CKD will hopefully accelerate discoveries and treatments to ameliorate muscle wasting as well as the progression of CKD.