title: Exploring the reverse J-shaped curve between urea reduction ratio and mortality.
abstract: BACKGROUND
  Although accepted worldwide as valid measures of dialysis adequacy, neither the Kt/V (urea clearance determined by kinetic modeling) nor the urea reduction ratio (URR) have unambiguously predicted survival in hemodialysis 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 proxy for skeletal muscle mass and nutritional health, we hypothesized that the increase in the relative risk of death observed among individuals dialyzed 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 analysis were stratified into quintiles of URR. Laboratory indicators of nutritional status and two bioimpedance-derived parameters, phase angle and estimated total body water, were compared across quintiles. The relationship between dialysis dose and mortality was explored, with a focus on how V influenced the structure of the dose-mortality relationship.
  
  
  RESULTS
  There were statistically significant differences in all nutritional parameters across quintiles of URR or Kt/V, indicating that patients in the 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 relationship between URR and mortality was decidedly curvilinear, resembling a reverse 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-mortality relationship. There was no evidence of an increase in the relative risk of death among patients treated with high Kt. Higher Kt was associated with a better nutritional status.
  
  
  CONCLUSIONS
  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 reflects a deleterious effect of malnutrition (manifest by a reduced V) that overcomes 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 protein-calorie malnutrition may limit the utility of URR or Kt/V as a population-based measure of dialysis dose.
authors.affiliation: Division of Nephrology, University of California, San Francisco, 94143, USA. chertowg@medicine.ucsf.edu
authors.forename: G M
authors.initials: GM
authors.lastname: Chertow
authors.forename: W F
authors.initials: WF
authors.lastname: Owen
authors.forename: J M
authors.initials: JM
authors.lastname: Lazarus
authors.forename: N L
authors.initials: NL
authors.lastname: Lew
authors.forename: E G
authors.initials: EG
authors.lastname: Lowrie
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009748:Nutrition Disorders / Q000378:metabolism; D009752:Nutritional Status; D006435:Renal Dialysis / Q000401:mortality*; D014508:Urea / Q000378:metabolism*
chemical_list: D014508:Urea