Latency and crescendo of uremic Milieu

Abstract

Preventing protein–energy wasting is a challenging task in chronic kidney disease (KD). It was in the 1930s that Rudolph Schoenheimer discovered that skeletal muscle is in a state of continual turnover. In a normal adult, 3.5–4.5 g protein/kg body weight is synthesized and degraded each day, and the majority of these proteins are intracellular proteins.[1] Simple mathematics implies that in a healthy human weighing 70 kg and consuming 1 g/kg/day of protein, 280 g of protein is synthesized every day which is four times the body weight. However, when catabolic conditions are present, skeletal muscle is degraded at an accelerated rate. In chronic KD, to a certain extent, treatment outcome and mortality are related to loss of muscle mass, which springs two questions: (i) how are protein stores lost? and (ii) how can the losses be prevented? Loss of muscle protein stores can result from three major responses, namely, (i) impaired growth of new muscle fibers, (ii) suppression of protein synthesis, and (iii) stimulation of protein degradation. In chronic KD, reduction in protein pool stores begins with uremia-induced protein breakdown on account of loss of appetite, taste, and smell, leading to decreased food intake; elevated levels of uremic toxins such as middle molecules and leptin; reduced levels of ghrelin; growth hormone synthesis; impaired insulin-like growth factor 1 axis; acidemia; increased insulin resistance; decreased insulin sensitivity; increased cortisol, aldosterone, and angiotensin II; and increased cytokine levels, which emerge from uremic milieu and trigger aforementioned major responses.