Red Cell Distribution Width and Mortality in Hemodialysis Patients.

BACKGROUND: Red cell distribution width (RDW) is an index of red blood cell volume variability that has historically been used as a marker of iron deficiency anemia. More recently, studies have shown that elevated RDW is associated with higher mortality risk in the general population. However, there is lack of data demonstrating the association between RDW and mortality risk in hemodialysis (HD) patients. We hypothesized that higher RDW is associated with higher mortality in HD patients. STUDY DESIGN: Retrospective observational study using a large HD patient cohort. SETTING & PARTICIPANTS: 109,675 adult maintenance HD patients treated in a large dialysis organization from January 1, 2007, to December 31, 2011. PREDICTOR: Baseline and time-varying RDW, grouped into 5 categories: <14.5%, 14.5% to <15.5%, 15.5% to <16.5%, 16.5% to <17.5%, and ≥17.5%. RDW of 15.5% to <16.5% was used as the reference category. OUTCOME: All-cause mortality. RESULTS: Mean age of study participants was 63±15 (SD) years and the study cohort was 44% women. In baseline and time-varying analyses, there was a graded association between higher RDW and incrementally higher mortality risk. Receiver operating characteristic, net reclassification analysis, and integrated discrimination improvement analyses demonstrated that RDW is a stronger predictor of mortality as compared with traditional markers of anemia, such as hemoglobin, ferritin, and iron saturation values. LIMITATIONS: Lack of comprehensive data that may be associated with both RDW and HD patient outcomes, such as blood transfusion data, socioeconomic status, and other unknown confounders; therefore, the possibility of residual confounding could not be excluded. Also, lack of information for cause of death; thus, cardiovascular mortality outcomes could not be examined. CONCLUSIONS: In HD patients, higher RDW is associated with incrementally higher mortality risk. RDW is also a stronger predictor of mortality than traditional laboratory markers of anemia. Further studies are needed to determine the mechanisms underlying the association between RDW and mortality.

Effect of age and dialysis vintage on obesity paradox in long-term hemodialysis patients.

BACKGROUND: In contrast to the general population, higher body mass index (BMI) is associated with greater survival in patients receiving hemodialysis (HD; "obesity paradox"). We hypothesized that this paradoxical association between BMI and death may be modified by age and dialysis vintage. STUDY DESIGN: Retrospective observational study using a large HD patient cohort. SETTING & PARTICIPANTS: 123,383 maintenance HD patients treated in DaVita dialysis clinics between July 1, 2001, and June 30, 2006, with follow-up through September 30, 2009. PREDICTORS: Age, dialysis vintage, and time-averaged BMI. Time-averaged BMI was divided into 6 subgroups; <18.5, 18.5-<23.0, 23.0-<25.0, 25.0-<30.0, 30.0-<35.0, and ≥35.0kg/m(2). BMI category of 23-<25kg/m(2) was used as the reference category. OUTCOMES: All-cause, cardiovascular, and infection-related mortality. RESULTS: Mean BMI of study participants was 27±7kg/m(2). Time-averaged BMI was <18.5 and ≥35kg/m(2) in 5% and 11% of patients, respectively. With progressively higher time-averaged BMI, there was progressively lower all-cause, cardiovascular, and infection-related mortality in patients younger than 65 years. In those 65 years or older, even though overweight/obese patients had lower mortality compared with underweight/normal-weight patients, sequential increases in time-averaged BMI > 25kg/m(2) added no additional benefit. Based on dialysis vintage, incident HD patients had greater all-cause and cardiovascular survival benefit with a higher time-averaged BMI compared with the longer term HD patients. LIMITATIONS: Causality cannot be determined, and residual confounding cannot be excluded given the observational study design. CONCLUSIONS: Higher BMI is associated with lower death risk across all age and dialysis vintage groups. This benefit is more pronounced in incident HD patients and those younger than 65 years. Given the robustness of the survival advantage of higher BMI, examining interventions to maintain or even increase dry weight in HD patients irrespective of age and vintage are warranted.

A comparative effectiveness research study of the change in blood pressure during hemodialysis treatment and survival.

It is not clear to what extent changes in blood pressure (BP) during hemodialysis affect or predict survival. Studying comparative outcomes of BP changes during hemodialysis can have major clinical implications including the impact on management strategies in hemodialysis patients. Here we undertook a retrospective cohort study of 113,255 hemodialysis patients over a 5-year period to evaluate an association between change in BP during hemodialysis and mortality. The change in BP was defined as post-hemodialysis minus pre-hemodialysis BP, and mean of BP change values during the hemodialysis session was used as a mortality predictor. The patients' average age was 61 years old and consisted of 45% women, 32% African-Americans and 58% diabetics. Over a median follow-up of 2.2 years, a total of 53,461 (47.2%) all-cause and 21,548 (25.7%) cardiovascular deaths occurred. In a fully adjusted Cox regression model with restricted cubic splines, there was a U-shaped association between change in systolic BP and all-cause mortality. Post-dialytic drops in systolic BP between -30 and 0 mm Hg were associated with greater survival, but large decreases of systolic BP (more than -30 mm Hg) and any increase in systolic BP (over 0 mm Hg) were related to increased mortality. Peak survival was found at a change in systolic BP of -14 mm Hg. The U-shaped association was also found for cardiovascular mortality. Thus, modest declines in BP after hemodialysis are associated with the greatest survival, whereas any rise or large decline in BP is associated with worsened survival.

Dialysis modality and correction of uremic metabolic acidosis: relationship with all-cause and cause-specific mortality.

BACKGROUND AND OBJECTIVES: Uremic metabolic acidosis is only partially corrected in many hemodialysis patients, and low serum bicarbonate predicts higher death risk. This study determined the comparative efficacy of peritoneal dialysis in correcting uremic metabolic acidosis and the association of serum bicarbonate and death risk with the two therapies. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data were obtained from 121,351 prevalent ESRD patients (peritoneal dialysis, 10,400; hemodialysis, 110,951) treated in DaVita facilities between July 1, 2001 and June 30, 2006, with follow-up through June of 2007. RESULTS: Serum bicarbonate was <22 mEq/L in 25% and 40% of peritoneal dialysis and hemodialysis patients, respectively. Thus, peritoneal dialysis patients were substantially less likely to have lower serum bicarbonate (adjusted odds ratio<20 mEq/L, 0.45 [0.42, 0.49]; <22 mEq/L, 0.41 [0.39, 0.43]). Time-averaged serum bicarbonate<19 mEq/L was associated with an 18% and 25% higher risk for all-cause and cardiovascular mortality, respectively, in prevalent peritoneal dialysis patients (reference group: serum bicarbonate between 24 and <25 mEq/L). In analyses using the entire cohort of peritoneal dialysis and hemodialysis patients, the adjusted risk for all-cause mortality was higher in most subgroups with serum bicarbonate<22 mEq/L, irrespective of dialysis modality. CONCLUSIONS: The measured bicarbonate is significantly higher in peritoneal dialysis patients, suggesting that the therapy provides a more complete correction of metabolic acidosis than intermittent hemodialysis. Survival data suggest maintaining serum bicarbonate>22 mEq/L for all ESRD patients, irrespective of dialysis modality.

Serum potassium and cause-specific mortality in a large peritoneal dialysis cohort.

BACKGROUND AND OBJECTIVES: Unlike hemodialysis (HD), peritoneal dialysis (PD) is a continuous therapy and does not induce myocardial stunning. Yet, the death risk in HD and PD patients is similar. This study tested the hypothesis that serum potassium abnormalities contribute more to the death risk in PD patients than in HD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data from patients treated in DaVita facilities between July 1, 2001 and June 30, 2006 (n=10,468 PD patients; n=111,651 HD patients) were used to determine association of serum potassium with mortality. RESULTS: PD patients were significantly more likely to have serum potassium < 4 mEq/L, with an adjusted odds ratio of 3.30 (95% confidence interval [95% CI], 3.05, 3.56). There was a U-shaped relationship between time-averaged serum potassium and all-cause and cardiovascular mortality of PD patients, with adjusted hazards ratios of 1.51 for all-cause mortality for potassium < 3.5 mEq/L (95% CI, 1.29, 1.76) and 1.52 for potassium ≥ 5.5 mEq/L (95% CI, 1.32, 1.75). The population-attributable risks for all-cause mortality for serum potassium < 4.0 and ≥ 5.5 mEq/L were 3.6% and 1.9%, respectively, in PD patients, and 0.8% and 1.5%, respectively, in HD patients. CONCLUSIONS: Abnormalities in serum potassium contribute disproportionately to the high death risk in PD patients. This may, in part, account for the equivalent cardiac risk seen with the two therapies.