Malnutrition, Inflammation and Reverse Epidemiology in Hemodialysis Patients

Reverse epidemiology, or risk factor paradox, has been used to describe the observed effect that traditional risk factors for cardiovascular disease may not necessarily signify the same risk for hemodialysis patients (HP) as for healthy populations. In fact, recent published findings have suggested counter-intuitive outcomes (Chavalitdhamrong, Danovitch, & Bunnapradist, 2007; Tsirpanlis et al., 2009) regarding the role cholesterol may play in disease progression in HP with chronic inflammation and malnutrition comorbidities (Dungan, Guster, DeWalt, & Buse, 2007). However, contemporary experimental studies regarding reverse epidemiology are lacking. The few published findings on this topic suggest chronic inflammation, as measured by C-reactive protein (CRP), and malnutrition, as measured by albumin, is associated with normal cholesterol levels yet higher levels of mortality (Chavalitdhamrong, et al., 2007; Chmielewski, Carrero, Nordfors, Lindholm, & Stenvinkel, 2008). In contrast, traditional risk factors such dyslipidemia, hyperhomocysteinemia, obesity, or hypertension may provide protective effects in HP, at least in the short term (KalantarZadeh, Block, Humphreys, & Kopple, 2003). Important predictors of clinical outcomes in HP are protein-energy wasting (malnutrition) (PEM) and inflammation (Fleischmann, Bower, & Salahudeen, 2001; Kalantar-Zadeh & Kopple, 2001; Kopple, 1997; Kopple, Zhu, Lew, & Lowrie, 1999; Lowrie & Lew, 1990; Nishizawa, Shoji, Ishimura, Inaba, & Morii, 2001). Because inflammation and PEM are interconnected and similarly affect markers of nutritional status both are considered part of a malnutrition inflammation complex (MIC) (Kalantar-Zadeh, et al., 2003; Kalantar-Zadeh & Kopple, 2001; Kalantar-Zadeh, Kopple, Block, & Humphreys, 2001). Thus, this chapter will address inflammation, malnutrition, cholesterol, and the overall concept of reverse epidemiology in HP relative to MIC as well as the implications of this information on shortand long-term treatment.