Reversing the risk factor paradox: is daily nocturnal hemodialysis the solution?

Reverse epidemiology or risk factor paradox refers to observations that traditional cardiovascular risk factors may not portend the same poor outcomes in the end-stage renal disease (ESRD) population, and may even be protective. If the underlying cause of this paradox is the "unphysiology" of the uremic milieu, as exemplified by the malnutrition-inflammation-complex syndrome, oxidative stress, and other aberrations of normal physiology, we propose that correcting this "unphysiology" could normalize the relationship between the traditional risk factors and their corresponding outcomes. In this review we summarize the growing body of evidence suggesting that daily nocturnal hemodialysis (NHD), a novel intensive form of home-based renal replacement therapy, normalizes many physiological processes, in an effort to support the hypothesis that NHD may reverse the risk factor paradox.