UC Irvine

Protein-energy malnutrition (PEM) and inflammation are common in patients with chronic kidney disease (CKD) and worsen as the CKD progresses toward the end-stage renal disease (ESRD). These conditions are major predictors of poor clinical outcome in kidney failure, as reflected by a strong association between hypoalbuminemia and cardiovascular disease (CVD). It has been suggested that inflammation is the cause of both PEM and CVD and, hence, the main link among these conditions, but these hypotheses are not well established. Increased release or activation of inflammatory cytokines, such as interleukin-6 or tumor necrosis factor alpha, may suppress appetite, cause muscle proteolysis and hypoalbuminemia, and may be involved in atherogenesis. Increasing serum levels of proinflammatory cytokines caused by reduced renal function, volume overload, oxidative or carbonyl stress, decreased levels of antioxidants, increased susceptibility to infection in uremia, and the presence of comorbid conditions may lead to inflammation in CKD patients. In hemodialysis patients, the exposure to dialysis tubing and dialysis membranes, poor quality of dialysis water, back-filtration or back-diffusion of contaminants, and foreign bodies in dialysis access maybe additional causes of inflammation. Similarly, episodes of overt or latent peritonitis, peritoneal dialysis (PD) catheter and its related infections, and constant exposure to PD solution may contribute to inflammation in these patients. The degree to which PEM in dialysis patients is caused by inflammation is not clear. Because both PEM and inflammation are strongly associated with each other and can change many nutritional measures and outcome concurrently in the same direction, the terms malnutrition-inflammation complex syndrome (MICS) and/or malnutrition-inflammation-atherosclerosis (MIA) have been suggested to denote the important contribution of both of these conditions to poor clinical outcome. Maintenance dialysis patients who are underweight or who have low serum levels of cholesterol, creatinine, or homocysteine may be suffering from the MICS/MIA and its subsequent poor outcome. Consequently, obesity and hypercholesterolemia may appear protective, which is known as reverse epidemiology. Although MICS/MIA may have a significant contribution in reversing the traditional CVD risk factors in dialysis patients, it is not clear whether PEM or inflammation and their complications can be effectively managed in CKD and ESRD or whether their management improves clinical outcome.