Inflammation and Protein-Energy Wasting in the Uremic Milieu

Inflammation is normally a protective and physiological response to harmful stimuli, but typically becomes an uncontrolled, maladaptive, and persistent process in patients with end-stage renal disease (ESRD). Through a deleterious cascade of poorly controlled reactions mediated by biologically active molecules (also called middle molecular weight uremia retention solutes), inflammation associates with a range of complications including cardiovascular disease and protein-energy wasting (PEW). Persistent inflammation, which is central to the conceptual etiological models of PEW and the malnutrition, inflammation, and atherosclerosis syndrome, induces and reignites processes leading to PEW in a number of ways including stimulation of both direct and indirect mechanisms of muscle proteolysis. Similar to other chronic diseases, inflammation in the uremic milieu is the consequence of multiple factors including comorbidities, such as infections. In addition, inflammation is further aggravated in ESRD by uremic immune dysfunction, inadequate renal removal of cytokines, and inflammatory responses to dialysis. It is plausible that only by disrupting this vicious circle(s) by acting on several levels of the inflammatory cascade rather than targeting single causes of inflammation will it be possible to improve the prognosis in ESRD patients. Accordingly, treatment of uremic inflammation and PEW require an integrated approach. In addition to lifestyle modifications, nutritional supplements, and drugs with anti-inflammatory potential, improved dialysis therapy using high retention onset membranes has emerged recently. This novel dialysis technique, also called expanded hemodialysis (HDx), may provide a more efficient removal of middle molecules involved in the cascade of inflammatory mediators with selectivity against albumin losses. Plausibly, the implementation of HDx, integrated with strategies blocking an excessive secretion of inflammatory mediators, may offer a new therapeutic approach to chronic inflammation and PEW in ESRD.