Exploring the reverse J-shaped curve between urea reduction ratio and mortality

Background. Although accepted worldwide as valid measures of dialysis adequ acy, neither the Kt/V (urea clearance determined by kinetic modeling) nor t he urea reduction ratio (URR) have unambiguously predicted survival in hemo dialysis patients. Because the ratio Kt/V can be high with either high Kt ( clearance x time) or low V (urea volume of distribution) and V may be a pro xy for skeletal muscle mass and nutritional health. we hypothesized that th e increase in the relative risk of death observed among individuals dialyze d in the top 10 to 20% of URR or Kt/V values might reflect a competing risk of malnutrition. Methods. A total of 3,009 patients who underwent bioelectrical impedance an alysis were stratified into quintiles of URR. Laboratory indicators of nutr itional status and two bioimpedance-derived parameters, phase angle and est imated total body water, were compared across quintiles. The relationship b etween dialysis dose and mortality was explored, with a focus on how V infl uenced the structure of the dose-mortality relationship. Results. There were statistically significant differences in all nutritiona l parameters across quintiles of URR or Kt/V, indicating that patients in t he fifth quintile (mean URR, 74.4 +/- 3.1%) were more severely malnourished on average than patients in all or some of the other quintiles. The relati onship between URR and mortality was decidedly curvilinear, resembling a re verse J shape that was confirmed by statistical analysis. An adjustment for the influence of V on URR or Kt/V was performed by evaluating the Kt-morta lity relationship. There was no evidence of an increase in the relative ris k of death among patients treated with high Kt. Higher Kt was associated wi th a better nutritional status. Conclusion. We conclude that the increase in mortality observed among those patients whose URR or Kt/V are among the top 10 to 20% of patients reflect s a deleterious effect of malnutrition (manifest by a reduced V) that overc omes whatever benefit might be derived from an associated increase in urea clearance. Identification of patients who achieve extremely high URR (>75%) or single-pooled Kt/V (>1.6) values using standard dialysis prescriptions should prompt a careful assessment of nutritional status. Confounding by pr otein-calorie malnutrition may limit the utility of URR or Kt/V as a popula tion-based measure of dialysis dose.