Background Identification of predictors of hyporesponsiveness to erythropoietin-stimulating agents (ESAs) in hemodialysis (HD) patients may help improve anemia management and reduce hemoglobin level ...variability. Study Design We conducted repeated-measure and logistic regression analyses in a retrospective cohort of long-term HD patients to examine the association of iron markers and measures of renal osteodystrophy with ESA responsiveness. The ESA response coefficient at the individual level, ie, the least confounded dose-response association, was separated from the population level, assumed to represent confounding by medical indication. Setting/Participants The national database of a large dialysis organization (DaVita Inc, El Segundo, CA) with 38,328 surviving prevalent HD patients during 12 months who received ESA for at least 3 consecutive calendar quarters was examined. Predictors Serum levels of ferritin, iron saturation ratio, intact parathyroid hormone, and alkaline phosphatase. Outcomes/Other Measurements The main outcome was case-mix–adjusted hemoglobin response to quarterly averaged ESA dose at the individual level. The odds ratio (OR) of the greatest versus poorest ESA-response quartile at the patient level was calculated. OR less than 1.0 indicated ESA hyporesponsiveness, and OR greater than 1.0, enhanced responsiveness. Results Mean ESA-response coefficients of the least to most responsive quartiles were 0.301 ± 0.033 (SD), 0.344 ± 0.004, 0.357 ± 0.004, and 0.389 ± 0.026 g/dL greater hemoglobin level per 1,000 U/wk greater ESA dose in each quarter, respectively. The ORs of greatest versus poorest ESA responsiveness at the patient level were serum ferritin level less than 200 ng/mL (0.77; 95% confidence interval CI, 0.70 to 0.86; reference, 200 to 500 ng/mL), iron saturation ratio less than 20% (0.54; 95% CI, 0.49 to 0.59; reference, 20% to 30%), intact parathyroid hormone level of 600 pg/mL or greater (0.54; 95% CI, 0.49 to 0.60; reference, 150 to 300 pg/mL), and alkaline phosphatase level of 160 IU/L or greater (0.64; 95% CI, 0.58 to 0.70; reference, 80 to 120 IU/L). Lower estimated dietary protein intake and serum levels of nutritional markers were also associated with greater risk of ESA hyporesponsiveness. Limitations Our results may incorporate uncontrolled confounding. Achieved hemoglobin level may have different associations than targeted hemoglobin level. Conclusions In long-term HD patients, low iron stores, hyperparathyroidism, and high-turnover bone disease are associated with significant ESA hyporesponsiveness. Prospective studies are needed to verify these associations.
OBJECTIVE To determine whether dry weight gain accompanied by an increase in muscle mass is associated with a survival benefit in patients receiving maintenance hemodialysis (HD). PATIENTS AND ...METHODS In a nationally representative 5-year cohort of 121,762 patients receiving HD 3 times weekly from July 1, 2001, through June 30, 2006, we examined whether body mass index (BMI) (calculated using 3-month averaged post-HD dry weight) and 3-month averaged serum creatinine levels (a likely surrogate of muscle mass) and their changes over time were predictive of mortality risk. RESULTS In the cohort, higher BMI (up to 45) and higher serum creatinine concentration were incrementally and independently associated with greater survival, even after extensive multivariate adjustment for available surrogates of nutritional status and inflammation. Dry weight loss or gain over time exhibited a graded association with higher rates of mortality or survival, respectively, as did changes in serum creatinine level over time. Among the 50,831 patients who survived the first 6 months and who had available data for changes in weight and creatinine level, those who lost weight but had an increased serum creatinine level had a greater survival rate than those who gained weight but had a decreased creatinine level. These associations appeared consistent across different demographic groups of patients receiving HD. CONCLUSION In patients receiving long-term HD, larger body size with more muscle mass appears associated with a higher survival rate. A discordant muscle gain with weight loss over time may confer more survival benefit than weight gain while losing muscle. Controlled trials of muscle-gaining interventions in patients receiving HD are warranted.
The association between pretransplant body composition and posttransplant outcomes in renal transplant recipients is unclear. It was hypothesized that in hemodialysis patients higher muscle mass ...(represented by higher pretransplant serum creatinine level) and larger body size (represented by higher pretransplant body mass index BMI) are associated with better posttransplant outcomes.
Linking 5-year patient data of a large dialysis organization (DaVita) to the Scientific Registry of Transplant Recipients, 10,090 hemodialysis patients were identified who underwent kidney transplantation from July 2001 to June 2007. Cox regression hazard ratios and 95% confidence intervals of death and/or graft failure were estimated.
Patients were 49 ± 13 years old and included 49% women, 45% diabetics, and 27% African Americans. In Cox models adjusted for case-mix, nutrition-inflammation complex, and transplant-related covariates, the 3-month-averaged postdialysis weight-based pretransplant BMI of 20 to <22 and < 20 kg/m(2), compared with 22 to <25 kg/m(2), showed a nonsignificant trend toward higher combined posttransplant mortality or graft failure, and even weaker associations existed for BMI ≥ 25 kg/m(2). Compared with pretransplant 3-month- averaged serum creatinine of 8 to <10 mg/dl, there was 2.2-fold higher risk of combined death or graft failure with serum creatinine <4 mg/dl, whereas creatinine ≥14 mg/dl exhibited 22% better graft and patient survival.
Pretransplant obesity does not appear to be associated with poor posttransplant outcomes. Larger pretransplant muscle mass, reflected by higher pretransplant serum creatinine level, is associated with greater posttransplant graft and patient survival.
Several observational studies have demonstrated that serum levels of minerals and parathyroid hormone (PTH) have U- or J-shaped associations with mortality in maintenance hemodialysis patients, but ...the relationship between serum alkaline phosphatase (AlkPhos) and risk for all-cause or cardiovascular death is unknown. In this study, a 3-yr cohort of 73,960 hemodialysis patients in DaVita outpatient dialysis were studied, and the hazard ratios for all-cause and cardiovascular death were higher across 20-U/L increments of AlkPhos, including within the various strata of intact PTH and serum aspartate aminotransferase. In the fully adjusted model, which accounted for demographics, comorbidity, surrogates of malnutrition and inflammation, minerals, PTH, and aspartate aminotransferase, AlkPhos > or =120 U/L was associated with a hazard ratio for death of 1.25 (95% confidence interval 1.21 to 1.29; P < 0.001). This association remained among diverse subgroups of hemodialysis patients, including those positive for hepatitis C antibody. A rise in AlkPhos by 10 U/L during the first 6 mo was incrementally associated with increased risk for death during the subsequent 2.5 yr. In summary, high levels of serum AlkPhos, especially >120 U/L, are associated with mortality among hemodialysis patients. Prospective controlled trials will be necessary to test whether serum AlkPhos measurements could be used to improve the management of renal osteodystrophy.
Protein-energy wasting, inflammation and refractory anemia are common in long-term hemodialysis patients. A decreased responsiveness to erythropoiesis-stimulating agents (ESA) is often the cause of ...the refractory anemia. We hypothesized that the malnutrition-inflammation complex is an independent predictor of decreased responsiveness to ESAs in hemodialysis patients.
This cohort study of 754 hemodialysis patients was examined for an association between inflammatory and nutritional markers, including the malnutrition-inflammation score (MIS) and responsiveness to ESA. Cubic spline models were fitted to verify found associations.
The mean (±SD) age of patients was 54 ± 15 years, 53% were diabetic and 32% blacks. MIS was worse in the highest quartile of ESAs responsiveness index (ERI, ESA dose divided by hemoglobin) when compared with 1st quartile (6.5 ± 4.5 versus 4.4 ± 3.4; P < 0.001). Both C-reactive protein (log CRP) (β = 0.19) and interleukin-6 (log IL-6) (β = 0.32) were strong and independent predictors of ERI using multivariate linear regression. Serum albumin (β = -0.30) and prealbumin levels (β = -0.14) were inversely associated with ERI. Each 1 SD higher MIS, higher CRP and lower albumin were associated with 86, 44 and 97% higher likelihood of having highest versus three lowest ERI quartiles in fully adjusted models odds ratio (and 95% confidence interval) of 1.86 (1.31-2.85), 1.44 (1.08-1.92) and 1.97 (1.41-2.78), respectively. Cubic splines confirmed the continuous and incremental nature of these associations.
Malnutrition-inflammation complex is an incremental predictor of poor responsiveness to ESAs in hemodialysis patients. Further studies are needed to assess whether modulating inflammatory or nutritional processes can improve anemia management.
Background Medication nonadherence is a known risk factor for adverse outcomes in the general population. However, little is known about the association of predialysis medication adherence among ...patients with advanced chronic kidney disease and mortality following their transition to dialysis. Study Design Observational study. Setting & Participants 32,348 US veterans who transitioned to dialysis during 2007 to 2011. Predictors Adherence to treatment with cardiovascular drugs, ascertained from pharmacy database records using proportion of days covered (PDC) and persistence during the predialysis year. Outcomes Post–dialysis therapy initiation all-cause and cardiovascular mortality, using Cox models with adjustment for confounders. Results Mean age of the cohort was 72 ± 11 (SD) years; 96% were men, 74% were white, 23% were African American, and 69% had diabetes. During a median follow-up of 23 (IQR, 9-36) months, 18,608 patients died. Among patients with PDC > 80%, there were 14,006 deaths (mortality rate, 283 95% CI, 278-288/1,000 patient-years); among patients with PDC > 60% to 80%, there were 3,882 deaths (mortality rate, 294 95% CI, 285-304/1,000 patient-years); among patients with PDC ≤ 60%, there were 720 deaths (mortality rate, 291 95% CI, 271-313/1,000 patient-years). Compared with patients with PDC > 80%, the adjusted HR for post–dialysis therapy initiation all-cause mortality for patients with PDC > 60% to 80% was 1.12 (95% CI, 1.08-1.16), and for patients with PDC ≤ 60% was 1.21 (95% CI, 1.11-1.30). In addition, compared with patients showing medication persistence, adjusted HR risk for post–dialysis therapy initiation all-cause mortality for patients with nonpersistence was 1.11 (95% CI, 1.05-1.16). A similar trend was detected for cardiovascular mortality and in subgroup analyses. Limitations Large number of missing values; results may not be generalizable to women or the general US population. Conclusions Predialysis cardiovascular medication nonadherence is an independent risk factor for postdialysis mortality in patients with advanced chronic kidney disease transitioning to dialysis therapy. Further studies are needed to assess whether interventions targeting adherence improve survival after dialysis therapy initiation.
Controlling serum potassium is an important goal in maintenance hemodialysis patients. We examined the achievement of potassium balance through hemodialysis treatments and the associated fluctuations ...in serum potassium.
A 3-yr (July 2001 to June 2004) cohort of 81,013 maintenance hemodialysis patients from all DaVita dialysis clinics across the United States were studied. Nine quarterly-averaged serum potassium groups (< 4.0, > or = 6.3 mEq/L and seven increments in-between) and four dialysate potassium concentration groups were created in each of the 12 calendar quarters. The death risk associated with predialysis potassium level and dialysate potassium concentration was examined using unadjusted, case-mix adjusted, and malnutrition-inflammation-adjusted time-dependent survival models.
Serum potassium correlated with nutritional markers. Serum potassium between 4.6 and 5.3 mEq/L was associated with the greatest survival, whereas potassium < 4.0 or > or = 5.6 mEq/L was associated with increased mortality. The death risk of serum potassium > or = 5.6 mEq/L remained consistent after adjustments. Higher dialysate potassium concentration was associated with increased mortality in hyperkalemic patients with predialysis serum potassium > or = 5.0 mEq/L.
A predialysis serum potassium of 4.6 to 5.3 mEq/L is associated with the greatest survival in maintenance hemodialysis patients. Hyperkalemic patients who undergo maintenance hemodialysis against lower dialysate bath may have better survival. Limitations of observational studies including confounding by indication should be considered when interpreting these results.
Abstract Objective To determine whether the association of body size and muscle mass with survival among patients undergoing long-term hemodialysis (HD) is consistent across race, especially in East ...Asian vs white and African American patients. Patients and Methods Using data from 20,818 patients from South Korea who underwent HD from February 1, 2001, to June 30, 2009, and 20,000 matched patients from the United States (10,000 whites and 10,000 African Americans) who underwent HD from July 1, 2001, to June 30, 2006, we compared mortality associations of baseline body mass index (BMI) and serum creatinine level as likely surrogates of obesity and muscle mass across the 3 races. Results In Korean HD patients, higher BMI together with higher serum creatinine levels were associated with greater survival, as previously reported from US and European studies. In the matched cohort (10,000 patients from each of the 3 races), mortality risks were lower across higher BMI and serum creatinine levels, and these associations were similar in all 3 races (reference groups: patients with BMI >25.0 kg/m2 or serum creatinine >12 mg/dL in each race). White, African American, and Korean patients with BMI levels of 18.5 kg/m2 or less (underweight) had 78%, 79%, and 57% higher mortality risk, respectively, and white, African American, and Korean patients with serum creatinine levels of 6.0 mg/dL or less had 108%, 87%, and 78% higher mortality, respectively. Conclusion This study shows that race does not modify the association of higher body size and muscle mass with greater survival in HD patients. Given the consistency of the obesity paradox, which may be related to a mitigated effect of protein-energy wasting on mortality irrespective of racial disparities, nutritional support to improve survival should be tested in HD patients of all races.
OBJECTIVE:--The optimal target for glycemic control has not been established in diabetic dialysis patients. RESEARCH DESIGN AND METHODS--To address this question, the national database of a large ...dialysis organization (DaVita) was analyzed via time-dependent survival models with repeated measures. RESULTS:--Of 82,933 patients undergoing maintenance hemodialysis (MHD) in DaVita outpatient clinics over 3 years (July 2001 through June 2004), 23,618 diabetic MHD patients had A1C measurements at least once. Unadjusted survival analyses indicated paradoxically lower death hazard ratios (HRs) with higher A1C values. However, after adjusting for potential confounders (demographics, dialysis vintage, dose, comorbidity, anemia, and surrogates of malnutrition and inflammation), higher A1C values were incrementally associated with higher death risks. Compared with A1C in the 5-6% range, the adjusted all-cause and cardiovascular death HRs for A1C >=10% were 1.41 (95% CI 1.25-1.60) and 1.73 (1.44-2.08), respectively (P < 0.001). The incremental increase in death risk for rising A1C values was monotonic and robust in nonanemic patients (hemoglobin >11.0 g/dl). In subgroup analyses, the association between A1C >6% and increased death risk was more prominent among younger patients, those who had undergone dialysis for >2 years, and those with higher protein intake (>1 g · kg⁻¹ · day⁻¹), blood hemoglobin (>11 g/dl), or serum ferritin values (>500 ng/ml). CONCLUSIONS:--In diabetic MHD patients, the apparently counterintuitive association between poor glycemic control and greater survival is explained by such confounders as malnutrition and anemia. All things equal, higher A1C is associated with increased death risk. Lower A1C levels not related to malnutrition or anemia appear to be associated with improved survival in MHD patients.
To investigate the association of estimated glomerular filtration rate (eGFR) slopes before dialysis initiation with cause-specific mortality after dialysis initiation.
In this retrospective cohort ...study of 18,874 US veterans who had transitioned to dialysis from October 1, 2007, through September 30, 2011, we examined the association of pre-end-stage renal disease (ESRD) eGFR slopes with all-cause, cardiovascular, and infection-related mortality during the post-ESRD period over a median follow-up of 2.0 years (interquartile range, 1.1-3.2 years). Associations were examined using Cox models with adjustment for potential confounders.
Before the 18,874 patients transitioned to dialysis, 4485 (23.8%), 5633 (29.8%), and 7942 (42.1%) experienced fast, moderate, and slow eGFR decline, respectively, and 814 (4.3%) had increasing eGFR (defined as eGFR slopes of less than -10, -10 to less than -5, -5 to <0, and ≥0 mL/min per 1.73 m(2) per year). During the study period, a total of 9744 all-cause, 2702 cardiovascular, and 604 infection-related deaths were observed. Compared with patients with slow eGFR decline, those with moderate and fast eGFR decline had a higher risk of all-cause mortality (adjusted hazard ratio HR, 1.06; 95% CI, 1.00-1.11; and HR, 1.11; 95% CI, 1.04-1.18, respectively) and cardiovascular mortality (HR, 1.11; 95% CI, 1.01-1.23 and HR, 1.13; 95% CI, 1.00-1.27, respectively). In contrast, increasing eGFR was only associated with higher infection-related mortality (HR, 1.49; 95% CI, 1.03-2.17).
Rapid eGFR decline is associated with higher all-cause and cardiovascular mortality, and increasing eGFR is associated with higher infection-related mortality among incident dialysis cases.
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