Protein Nutrition and Malnutrition in CKD and ESRD

Abstract

Elevated protein catabolism and protein malnutrition are common in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). The underlying etiology includes, but is not limited to, metabolic acidosis intestinal dysbiosis; systemic inflammation with activation of complements, endothelin-1 and renin-angiotensin-aldosterone (RAAS) axis; anabolic hormone resistance; energy expenditure elevation; and uremic toxin accumulation. All of these derangements can further worsen kidney function, leading to poor patient outcomes. Many of these CKD-related derangements can be prevented and substantially reversed, representing an area of great potential to improve CKD and ESRD care. This review integrates known information and recent advances in the area of protein nutrition and malnutrition in CKD and ESRD. Management recommendations are summarized. Thorough understanding the pathogenesis and etiology of protein malnutrition in CKD and ESRD patients will undoubtedly facilitate the design and development of more effective strategies to optimize protein nutrition and improve outcomes.

Keywords: protein  nutrition; acidosis; chronic  kidney  disease; dialysis; inflammation; protein  catabolism; hormonal derangements; uremic toxins.

Figure 1

Interconnection of CKD progression with metabolic acidosis, inflammation, hormonal resistance and protein catabolism. (A) Kidney dysfunction limits proton (H⁺) excretion, resulting in a systemic metabolic acidosis. The acidosis causes activation of complement systems, renin angiotensin aldosterone systems and endothelin-1. These acidosis-mediated effects cause CKD progression, forming a viscous cycle; (B) Acidosis promotes inflammation and tissue resistance to multiple anabolic hormones and simultaneously enhances activity of catabolic corticosteroids. Protein catabolism generates acidic products, contributing to acidosis in the setting of CKD and ESRD. Collectively, these abnormalities give rise to a state of protein catabolism, causing sustained negative nitrogen balance, leading to muscle wasting.

Figure 2

Kidney-intestinal axis: Gastrointestinal-related inflammation and uremic toxin generation in CKD and ESRD. With progressive decline in kidney function, cytokine production and half-life increases while cytokine elimination decreases. CKD patients frequently have comorbidities (diabetes, hypertension, cardiovascular diseases, anemia and hyperphosphatemia) and are on multiple medications including diuretics (often with fluids restriction), iron preparations, phosphate binders and more that can slow bowel transit and cause constipation. With imposed dietary restrictions for CKD and ESRD, they tend to be on a diet low in fiber that can affect gut motility. Slow intestinal transit plus bowel mucosa edema (occurs often when patients with worsening kidney dysfunction and cardiovascular abnormalities) could alter protein digestion and bowel flora. Proteolytic bacteria floras are preferentially selected over the saccarolytic bacteria. The predominant proteolytic bacteria ferment luminal proteins and generate toxic metabolites and ammonia. The toxic metabolites would disrupt intestinal mucosal barriers causing increasing bacteria and toxin translocation. The systemic exposure and accumulation of these toxins and bacteria causes a low-grade but persistent endotoxemia. Adequate gut flora is known to enhance bowel integrity and promote immunoregulatory function. Disruption of normal flora could compromise gut immune function and, in the extreme, create a situation of “immunoparalysis”. The consequence of these effects is systemic cytokine activation, accumulation of uremic toxins and endotoxemia (purple rectangle).