Chapter 1 - The Influence of Kidney Disease on Protein and Amino Acid Metabolism

Abstract

Chronic kidney disease (CKD) is associated with multiple defects in the metabolism of protein and amino acids. In response to CKD, the rates of protein synthesis and degradation are imbalanced with an increase in protein degradation resulting in net loss of protein stores, including the major quantity of protein in the body, skeletal muscle. Loss of protein stores in CKD patients contributes to the frequent occurrence of dependency, morbidity and mortality. These abnormalities persist even when the diet is improved indicating that protein abnormalities in CKD should not be assigned to malnutrition. Since proteins in all tissues are continually being degraded (principally through the ubiquitin-proteasome pathway and caspase-3) and replaced by new synthesis, the dysregulation of protein metabolism by CKD will contribute to the complications of CKD. Specific abnormalities causing muscle wasting have been defined and include metabolic acidosis, impaired intracellular signaling responses to insulin and IGF-1, increased angiotensin II levels and inflammatory cytokines. CKD also impairs the metabolism of branched-chain amino acids (BCAA), key “building blocks” of muscle protein and CKD leads to the accumulation of metabolic products of amino acids to contribute to toxic reactions, including changes in protein metabolism. A key mediator of muscle metabolic defects is an increase in myostatin, a negative regulator of muscle mass. Reversal of CKD-induced abnormalities such as metabolic acidosis, improve protein metabolism but newer strategies will be required to decrease the burden caused by the metabolic complications of CKD.