The target organ failures associated with uremia are most often considered to be caused by processes other than uremia per se. Heart disease, for example, is considered the product of hypertension, lipid abnormalities, and so forth, rather then the uremic state. Erythropoietin deficiency, blood loss, and iron deficiency are believed to cause anemia, rather than the uremic state. Malnutrition is believed to be the product of poor nutrient intake and perhaps nutrient losses, rather than uremia per se. This article reviews evidence suggesting that anemia and malnutrition share a common cause; the acute-phase inflammatory process that is a normal host-defense mechanism. Given the high prevalence of heart disease among patients with end-stage renal disease (ESRD), data indicating activation of the acute-phase process in patients with kidney failure, and emerging evidence that the process has a significant role in the risk for cardiovascular disease among patients without kidney failure, there is a strong likelihood that heart disease will share with anemia and malnutrition the acute-phase state as a contributing cause. Thus, instead of disconnected target organ failures, each with different antecedent causes, we see emerging the likelihood of a unifying pathobiology for uremia. The antecedents of morbidity and mortality appear as a web of organ failures connected by a common pathobiology. Whereas each failure likely has contributing causes other than the acute-phase state, they probably share the state as a causative, contributing, or exacerbating factor.