Outcome research, nutrition, and reverse epidemiology in maintenance dialysis patients☆

High morbidity and mortality of maintenance dialysis patients have led to an increase in interest in outcome research in an attempt to identify causes for this adverse outcome. It has been proposed that a substantial amount of this risk can be explained by protein energy malnutrition, chronic inflammation, or concurrent combination of both, known as malnutrition-inflammation complex syndrome (MICS). Elements of overnutrition, such as increased weight or high serum cholesterol levels, which are deleterious in the general population, paradoxically are protective in dialysis patients. Conversely, a low body mass index and low serum levels of cholesterol, creatinine, and possibly homocysteine are risk factors for poor outcome in dialysis-dependent populations. These reverse or paradoxical relationships between nutritional markers and outcome are referred to as reverse epidemiology. The MICS appears to be a main contributor to the reverse epidemiology and poor outcome. Mortality is the most definitive and objective clinical outcome, whereas hospitalization and quality of life (QoL) are additional relevant but somewhat less objective outcome measures in dialysis populations. A systematic classification of outcome measures and their related epidemiologic and statistical assessment tools in dialysis patients are reviewed. The effect of MICS on outcome can be examined by epidemiologic studies that are based on large samples of dialysis patients, use multivariate techniques, and, as long as they follow strict methodologic requirements, provide an invaluable economical alternative to expensive clinical trials.