Pruritus in Hemodialysis Patients: Longitudinal Associations With Clinical and Patient-Reported Outcomes.

RATIONALE & OBJECTIVE: Cross-sectional studies have reported an association of chronic kidney disease-associated pruritus (CKD-aP) with adverse clinical events and patient-reported outcomes (PROs). We studied the longitudinal associations between changes in CKD-aP and clinical outcomes among patients receiving maintenance hemodialysis. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 7,976 hemodialysis recipients across 21 countries in phases 4-6 (2009-2018) of the Dialysis Outcomes and Practice Patterns Study (DOPPS) who had 2 CKD-aP assessments approximately 12 months apart. EXPOSURES: Exposure status was based on the assessment of pruritis initially and again approximately 1 year later. Four groups were identified, including those with moderate or more severe pruritis only at the initial assessment (resolved), only at the second assessment (incident), at neither assessment (absent), or at both assessments (persistent). OUTCOMES: Laboratory values and PROs ascertained at the initial assessment of pruritis and 1 year later. ANALYTICAL APPROACH: Linear mixed model to investigate changes in laboratory values and PROs over the 1-year study period across the 4 exposure groups. RESULTS: 51% of patients had moderate to severe CKD-aP symptoms at either assessment (22% at both). The prevalences of depression, restless sleep, and feeling drained increased over the study period (+13%,+10%, and+14%, respectively) among patients with incident pruritus and decreased (-5%, -8%, and -12%, respectively) among patients with resolved pruritus. Minimal changes in PROs over time were observed for the absent and persistent groups. Changes over time in laboratory values (phosphorus, Kt/V) were not detected for either of these groups. Compared with patients with absent CKD-aP, the adjusted HRs for patients with persistent CKD-aP were 1.29 (95% CI, 1.09-1.53) for all-cause mortality, 1.17 (1.07-1.28) for all-cause hospitalization, and 1.48 (1.26-1.74) for cardiovascular events. LIMITATIONS: No interim evaluation of CKD-aP symptoms between the 2 assessments; potential selection bias from patients who died or were otherwise lost to follow-up before the second assessment. CONCLUSIONS: CKD-aP symptoms are chronic, and these findings highlight the potential value of repeated assessment of this symptom using standardized approaches. Future research should systematically investigate potential causes of CKD-aP and options for its effective treatment. PLAIN-LANGUAGE SUMMARY: Previous research has studied itching and its consequences in hemodialysis recipients only at a single time point. We surveyed 7,976 patients receiving maintenance hemodialysis to assess itching over a period of 1 year. We found that, among those experiencing itching at the initial assessment, more than half had persistent symptoms 1 year later. Those in whom itching developed during follow-up were more likely to experience depression, poor sleep, long recovery times after dialysis, and feeling faint or drained. These patients also rated their quality of life as poorer than those who did not experience itching. These findings emphasize the potential value of clinical detection of itching and the pursuit of effective treatments for patients receiving dialysis experiencing these symptoms.

Association of single and serial measures of serum phosphorus with adverse outcomes in patients on peritoneal dialysis: results from the international PDOPPS.

BACKGROUND: While high serum phosphorus levels have been related to adverse outcomes in hemodialysis patients, further investigation is warranted in persons receiving peritoneal dialysis (PD). METHODS: Longitudinal data (2014-17) from the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS), a prospective cohort study, were used to examine associations of serum phosphorus with all-cause mortality and major adverse cardiovascular events via Cox regression adjusted for confounders. Serum phosphorus levels were parameterized by four methods: (i) baseline serum phosphorus; (ii) mean 6-month serum phosphorus; (iii) number of months with serum phosphorus >4.5 mg/dL; and (iv) mean area-under-the-curve of 6-month serum phosphorus control. RESULTS: The study included 5847 PD patients from seven countries; 9% of patients had baseline serum phosphorus <3.5 mg/dL, 24% had serum phosphorus ≥3.5 to ≤4.5 mg/dL, 30% had serum phosphorus >4.5 to <5.5 mg/dL, 20% had serum phosphorus ≥5.5 to <6.5 mg/dL, and 17% had serum phosphorus ≥6.5 mg/dL. Compared with patients with baseline serum phosphorus ≥3.5 to ≤4.5 mg/dL, the adjusted all-cause mortality hazard ratio (HR) was 1.19 (0.92,1.53) for patients with baseline serum phosphorus ≥5.5 to <6.5 mg/dL and HR was 1.53 (1.14,2.05) for serum phosphorus ≥6.5 mg/dL. Associations between serum phosphorus measurements over 6 months and clinical outcomes were even stronger than for a single measurement. CONCLUSIONS: Serum phosphorus >5.5 mg/dL was highly prevalent (37%) in PD patients, and higher serum phosphorus levels were a strong predictor of morbidity and death, particularly when considering serial phosphorus measurements. This highlights the need for improved treatment strategies in this population. Serial serum phosphorus measurements should be considered when assessing patients' risks of adverse outcomes.

Receiving hemodialysis in Hispanic ethnic dense communities is associated with better adherence and outcomes among young patients: a retrospective analysis of the Dialysis Outcomes and Practice Patterns Study.

BACKGROUND: Hispanic ethnic density (HED) is a marker of better health outcomes among Hispanic patients with chronic disease. It is unclear whether community HED is associated with mortality risk among ethnically diverse patients receiving maintenance hemodialysis. METHODS: A retrospective analysis of patients in the United States cohort of the Dialysis Outcomes and Practice Patterns Study (DOPPS) database (2011-2015) was conducted (n = 4226). DOPPS data was linked to the American Community Survey database by dialysis facility zip code to obtain % Hispanic residents (HED). One way ANOVA and Kruskal Wallis tests were used to estimate the association between tertiles of HED with individual demographic, clinical and adherence characteristics, and facility and community attributes. Multivariable Cox proportional hazards models were used to estimate the mortality hazard ratio (HR) and 95% CIs by tertile of HED, stratified by age; a sandwich estimator was used to account for facility clustering. RESULTS: Patients dialyzing in facilities located in the highest HED tertile communities were younger (61.4 vs. 64.4 years), more commonly non-White (62.4% vs. 22.1%), had fewer comorbidities, longer dialysis vintage, and were more adherent to dialysis treatment, but had fewer minutes of dialysis prescribed than those in the lowest tertile. Dialyzing in the highest HED tertile was associated with lower hazard of mortality (HR, 0.86; 95% CI, 0.72-1.00), but this association attenuated with the addition of individual race/ethnicity (HR, 0.92; 95% CI, 0.78-1.09). In multivariable age-stratified analyses, those younger than 64 showed a lower hazard for mortality in the highest (vs. lowest) HED tertile (HR, 0.66; 95% CI, 0.49-0.90). Null associations were observed among patients ≥ 64 years. CONCLUSIONS: Treating in communities with greater HED and racial/ethnic integration was associated with lower mortality among younger patients which points to neighborhood context and social cohesion as potential drivers of improved survival outcomes for patients receiving hemodialysis.

Etelcalcetide Utilization, Dosing Titration, and Chronic Kidney Disease-Mineral and Bone Disease (CKD-MBD) Marker Responses in US Hemodialysis Patients.

RATIONALE & OBJECTIVE: Clinical trial data have demonstrated the efficacy of etelcalcetide for reducing parathyroid hormone (PTH) levels in hemodialysis (HD) patients. We provide a real-world summary of etelcalcetide utilization, dosing, effectiveness, and discontinuation since its US introduction in April 2017. STUDY DESIGN: New-user design within prospective cohort. SETTING & PARTICIPANTS: 2,596 new users of etelcalcetide from April 2017 through August 2019 in a national sample of adult maintenance HD patients in the US Dialysis Outcomes and Practice Patterns Study (DOPPS). PREDICTORS: Baseline PTH, prior cinacalcet use, initial etelcalcetide dose. OUTCOME: Trajectories of etelcalcetide dose, chronic kidney disease-mineral and bone disease (CKD-MBD) medications, and levels of PTH, serum calcium, and phosphorus in the 12 months after etelcalcetide initiation. ANALYTICAL APPROACH: Cumulative incidence methods for etelcalcetide discontinuation and linear generalized estimating equations for trajectory analyses. RESULTS: By August 2019, etelcalcetide prescriptions increased to 6% of HD patients from their first use in April 2017. Starting etelcalcetide dose was 15 mg/wk in 70% of patients and 7.5 mg/wk in 27% of patients; 49% of new users were prescribed cinacalcet in the prior 3 months. Etelcalcetide discontinuation was 9%, 17%, and 27% by 3, 6, and 12 months after initiation. One year after etelcalcetide initiation, mean PTH levels declined by 40%, from 948 to 566 pg/mL, and the proportion of patients with PTH within target (150-599 pg/mL) increased from 33% to 64% overall, from 0 to 60% among patients with baseline PTH ≥ 600 pg/mL, and from 30% to 63% among patients with prior cinacalcet use. The proportion of patients with serum phosphorus > 5.5 mg/dL decreased from 55% to 45%, while the prevalence of albumin-corrected serum calcium < 7.5 mg/dL remained at 1%-2%. There were increases in use of active vitamin D (from 77% to 87%) and calcium-based phosphate binders (from 41% to 50%) in the 12 months after etelcalcetide initiation. LIMITATIONS: Data are unavailable for provider dosing protocols, dose holds, or reasons for discontinuation. CONCLUSIONS: In the 12 months after etelcalcetide initiation, patients had large and sustained reductions in PTH levels. These results support the utility of etelcalcetide as an effective therapy to achieve the KDIGO-recommended guidelines for CKD-MBD markers in HD patients.

Resistance to Erythropoiesis-Stimulating Agents among Patients on Hemodialysis Is Typically Transient.

INTRODUCTION: This study examines factors associated with erythropoiesis-stimulating agent (ESA) hyporesponsiveness, the duration of ESA hyporesponsiveness, the frequency of new episodes, and variation across countries. METHODS: We used international Dialysis Outcomes and Practice Patterns Study data from 2015 to 2018 (N = 26,656) to investigate changes in ESA Resistance Index (ERI), calculated as epoetin dose divided by [hemoglobin × body weight] in patients on hemodialysis. We illustrated the proportion of patients who moved to other ERI quintiles over 12 months, and we studied the incidence and duration of ESA resistance. We examined case-mix factors associated with quintiles of ERI. RESULTS: Most patients migrated out of their original ERI quintile within 4 months. Only 22% of patients in the top quintile of ERI at baseline (4.4% of all patients) remained in the top quintile during all 12 months of follow-up. A total of 42% of patients manifested an upper-quintile ERI during at least 1 month. Median duration of a new episode of ESA resistance was 2 months. Catheter hemoaccess, elevated C-reactive protein, lower transferrin saturation, lower serum albumin concentration, and recent hospitalization occurred more frequently among patients in the highest ERI quintile at baseline. ERI values were highest in the USA, Italy, and Mideastern nations and lowest in Russia and Japan. DISCUSSION/CONCLUSION: It is a misconception to envision a sizable, fixed segment of the population with permanent resistance to ESA - resistance fluctuates frequently. The implications of these findings for prescription of ESAs and of hypoxia-inducible factor-prolyl hydroxylase inhibitors are discussed.

The risk of medically uncontrolled secondary hyperparathyroidism depends on parathyroid hormone levels at haemodialysis initiation.

BACKGROUND: Optimal parathyroid hormone (PTH) control during non-dialysis chronic kidney disease (ND-CKD) might decrease the subsequent risk of parathyroid hyperplasia and uncontrolled secondary hyperparathyroidism (SHPT) on dialysis. However, the evidence for recommending PTH targets and therapeutic strategies is weak for ND-CKD. We evaluated the patient characteristics, treatment patterns and PTH control over the first year of haemodialysis (HD) by PTH prior to HD initiation. METHODS: We studied 5683 incident HD patients from 21 countries in Dialysis Outcomes and Practice Patterns Study Phases 4-6 (2009-18). We stratified by PTH measured immediately prior to HD initiation and reported the monthly prescription prevalence of active vitamin D and calcimimetics over the first year of HD and risk of PTH >600 pg/mL after 9-12 months on HD. RESULTS: The 16% of patients with PTH >600 pg/mL prior to HD initiation were more likely to be prescribed active vitamin D and calcimimetics during the first year of HD. The prevalence of PTH >600 pg/mL 9-12 months after start of HD was greater for patients who initiated HD with PTH >600 (29%) versus 150-300 (7%) pg/mL (adjusted risk difference: 19%; 95% confidence interval : 15%, 23%). The patients with sustained PTH >600 pg/mL after 9-12 months on HD were younger, more likely to be black, and had higher serum phosphorus and estimated glomerular filtration rates at HD initiation. CONCLUSIONS: Increased PTH before HD start predicted a higher PTH level 9-12 months later, despite greater use of active vitamin D and calcimimetics. More targeted PTH control during ND-CKD may influence outcomes during HD, raising the need for PTH target guidelines in these patients.

Community Racial Composition and Hospitalization Among Patients Receiving In-Center Hemodialysis.

RATIONALE & OBJECTIVE: Community racial composition has been shown to be associated with mortality in patients receiving maintenenance dialysis. It is unclear whether living in communities with predominantly Black residents is also associated with risk for hospitalization among patients receiving hemodialysis. STUDY DESIGN: Retrospective analysis of prospectively collected data from a cohort of patients receiving hemodialysis. SETTING & PARTICIPANTS: 4,567 patients treated in 154 dialysis facilities located in 127 unique zip codes and enrolled in US Dialysis Outcomes and Practice Patterns Study (DOPPS) phases 4 to 5 (2010-2015). EXPOSURE: Tertile of percentage of Black residents within zip code of patients' dialysis facility, defined through a link to the American Community Survey. OUTCOME: Rate of hospitalizations during the study period. ANALYTIC APPROACH: Associations of patient-, facility-, and community-level variables with community's percentage of Black residents were assessed using analysis of variance, Kruskal-Wallis, or χ2/Fisher exact tests. Negative binomial regression was used to estimate the incidence rate ratio for hospitalizations between these communities, with and without adjustment for potential confounding variables. RESULTS: Mean age of study patients was 62.7 years. 53% were White, 27% were Black, and 45% were women. Median and threshold percentages of Black residents in zip codes in which dialysis facilities were located were 34.2% and≥14.4% for tertile 3 and 1.0% and≤1.8% for tertile 1, respectively. Compared with those in tertile 1 facilities, patients in tertile 3 facilities were more likely to be younger, be Black, live in urban communities with lower socioeconomic status, have a catheter as vascular access, and have fewer comorbid conditions. Patients dialyzing in communities with the highest tertile of Black residents experienced a higher adjusted rate of hospitalization (adjusted incidence rate ratio, 1.32; 95% CI, 1.12-1.56) compared with those treated in communities within the lowest tertile. LIMITATIONS: Potential residual confounding. CONCLUSIONS: The risk for hospitalization for patients receiving maintenance dialysis is higher among those treated in communities with a higher percentage of Black residents after adjustment for dialysis care, patient demographics, and comorbid conditions. Understanding the cause of this association should be a priority of future investigation.

Impact of longer term phosphorus control on cardiovascular mortality in hemodialysis patients using an area under the curve approach: results from the DOPPS.

BACKGROUND: Serial assessment of phosphorus is currently recommended by the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, but its additional value versus a single measurement is uncertain. METHODS: We studied data from 17 414 HD patients in the Dialysis Outcomes and Practice Patterns Study, a prospective cohort study, and calculated the area under the curve (AUC) by multiplying the time spent with serum phosphorus >4.5 mg/dL over a 6-month run-in period by the extent to which this threshold was exceeded. We estimated the association between the monthly average AUC and cardiovascular (CV) mortality using Cox regression. We formally assessed whether AUC was a better predictor of CV mortality than other measures of phosphorus control according to the Akaike information criterion. RESULTS: Compared with the reference group of AUC = 0, the adjusted hazard ratio (HR) of CV mortality was 1.12 [95% confidence interval (CI) 0.90-1.40] for AUC > 0-0.5, 1.26 (95% CI 0.99-1.62) for AUC > 0.5-1, 1.44 (95% CI 1.11-1.86) for AUC > 1-2 and 2.03 (95% CI 1.53-2.69) for AUC > 2. The AUC was predictive of CV mortality within strata of the most recent phosphorus level and had a better model fit than other serial measures of phosphorus control (mean phosphorus, months out of target). CONCLUSIONS: We conclude that worse phosphorus control over a 6-month period was strongly associated with CV mortality. The more phosphorus values do not exceed 4.5 mg/dL the better is survival. Phosphorus AUC is a better predictor of CV death than the single most recent phosphorus level, supporting with real-world data KDIGO's recommendation of serial assessment of phosphorus to guide clinical decisions.

Temporal changes in dialysate [Na+] prescription from 1996 to 2018 and their clinical significance as judged from a meta-regression of clinical trials.

Over the last two decades, the clinical care of dialysis patients has refocused sharply on fluid volume control. Dialysate [Na+] is a key, albeit under-investigated, clinical tool for manipulation of fluid volume on dialysis. In the article, we firstly use data from the Dialysis Outcomes and Practice Patterns Study to document the global decrease in dialysate [Na+] that has occurred from 1996 to 2018, and demonstrate the virtual disappearance of [Na+] profiling from routine dialysis practice over the same period. Second, we used data from previously synthesized randomized clinical trial evidence combined with that of a more recently published trail to assess the clinical significance of these changes, estimating the effects of different levels of low dialysate [Na+] on key clinical outcomes. Our analyses suggest that current levels of dialysate [Na+] in some health jurisdictions are possibly causing harm to many patients, especially given that real world populations are significantly less robust and more vulnerable than clinical trial ones. To quote a recent editorial, "more evidence needed before lower dialysate sodium concentrations can be recommended." That evidence is coming, and no further changes should be made to default customary practice until it is available.

The association between longer haemodialysis treatment times and hospitalization and mortality after the two-day break in individuals receiving three times a week haemodialysis.

BACKGROUND: On the first haemodialysis (HD) day after the 2-day break in three times a week (3×W) in-centre HD, mortality and hospitalization are higher. If longer HD sessions prescribed 3×W is associated with a reduction in these events is unknown. METHODS: HD session length in 19 557 prevalent European in-centre 3×W HD patients participating in the Dialysis Outcomes and Practice Patterns Study (1998-2011) were categorized into <200, 200-225, 226-250 or >250 min. Standardized event rates on the first (HD1) versus the second (HD2) HD day after the 2-day break, with supporting Cox proportional hazards models adjusted for patient and dialysis characteristics, were generated for all-cause mortality, all-cause hospitalization, out-of-hospital death and fluid overload hospitalization. RESULTS: By comparing HD1 with HD2, increased rates of all endpoints were observed (all P < 0.002). As HD session lengthened across the four groups, all-cause mortality per 100 patient-years on the HD1 (23.0, 20.4, 16.4 and 14.6) and HD2 (26.1, 13.3, 13.4 and 12.1) reduced. Similar improvements were observed for out-of-hospital death but were less marked for hospitalization endpoints. However, even patients dialysing >250 min were at significantly greater risk on HD1 when compared with their HD2 for out-of-hospital death [hazard ratio (HR) = 2.1, 95% CI 1.0-4.3], all-cause hospitalization (HR = 1.3, 95% CI 1.2-1.4) and fluid overload hospitalization (HR = 3.2, 95% CI 1.8-6.0). CONCLUSIONS: Despite the association between reduced mortality across all dialysis days in patients performing longer sessions, elevated risk on the first dialysis day relative to the second persists even in patients dialysing 4.5 h 3×W.

Patient-reported advantages and disadvantages of peritoneal dialysis: results from the PDOPPS.

BACKGROUND: Patient-reported measures are increasingly recognized as important predictors of clinical outcomes in peritoneal dialysis (PD). We sought to understand associations between patient-reported perceptions of the advantages and disadvantages of PD and clinical outcomes. METHODS: In this cohort study, 2760 PD patients in the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) completed a questionnaire on their PD experience, between 2014 and 2017. In this questionnaire, PDOPPS patients rated 17 aspects of their PD experience on a 5-category ordinal scale, with responses scored from - 2 (major disadvantage) to + 2 (major advantage). An advantage/disadvantage score (ADS) was computed for each patient by averaging their response scores. The ADS, along with each of these 17 aspects, were used as exposures. Outcomes included mortality, transition to hemodialysis (HD), patient-reported quality of life (QOL), and depression. Cox regression was used to estimate associations between ADS and mortality, transition to HD, and a composite of the two. Logistic regression with generalized estimating equations was used to estimate cross-sectional associations of ADS with QOL and depression. RESULTS: While 7% of PD patients had an ADS < 0 (negative perception of PD), 59% had an ADS between 0 and < 1 (positive perception), and 34% had an ADS ≥1 (very positive perception). Minimal association was observed between mortality and the ADS. Compared with a very positive perception, patients with a negative perception had a higher transition rate to HD (hazard ratio [HR] = 1.67; 95% confidence interval [CI]: 1.21, 2.30). Among individual items, "space taken up by PD supplies" was commonly rated as a disadvantage and had the strongest association with transition to HD (HR = 1.28; 95% CI 1.07, 1.53). Lower ADS was strongly associated with worse QOL rating and greater depressive symptoms. CONCLUSIONS: Although patients reported a generally favorable perception of PD, patient-reported disadvantages were associated with transition to HD, lower QOL, and depression. Strategies addressing these disadvantages, in particular reducing solution storage space, may improve patient outcomes and the experience of PD.

DOPPS data suggest a possible survival benefit of renin angiotensin-aldosterone system inhibitors and other antihypertensive medications for hemodialysis patients.

The benefits of renin angiotensin-aldosterone system inhibitors (RAASi) are well-established in the general population, particularly among those with diabetes, congestive heart failure (CHF), or coronary artery disease (CAD). However, conflicting evidence from trials and concerns about hyperkalemia limit RAASi use in hemodialysis patients, relative to other antihypertensive agents, including beta blockers and calcium channel blockers. Therefore, we investigated prescription patterns and associations with mortality for RAASi and other antihypertensive agents using data from the international Dialysis Outcomes and Practice Patterns Study (DOPPS). Cox regression was used to estimate the effect of the prescription of RAASi and other antihypertensive agents at study entry on mortality in 11,421 incident (120 days or less) hemodialysis and 37,124 prevalent (over 120 days) hemodialysis patients from DOPPS phases 2-5 (2002-2015). Over 95% of RAASi were angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. RAASi prevalence was 39% and varied minimally by CHF and CAD. The adjusted hazard ratio for RAASi (vs. no RAASi) was 0.89 (95% confidence interval 0.80-0.99) among incident and 0.94 (0.90-0.99) among prevalent hemodialysis patients, with no convincing evidence of interaction with diabetes, CAD or CHF. Inverse associations with mortality were also observed for beta blockers and calcium channel blockers, and were stronger for angiotensin receptor blockers than angiotensin-converting enzyme inhibitors, but this latter finding requires further study. Thus, our observations suggest a relatively small survival benefit of RAASi and other antihypertensive agents in hemodialysis patients, though randomized prospective studies are needed to potentially change prescribing criteria.

Association between serum ferritin and mortality: findings from the USA, Japan and European Dialysis Outcomes and Practice Patterns Study.

Background: The Kidney Disease: Improving Global Outcomes guidelines have cautioned against administering intravenous (IV) iron to hemodialysis patients with high serum ferritin levels due to safety concerns, but prior research has shown that the association between high ferritin and mortality could be attributed to confounding by malnutrition and inflammation. Our goal was to better understand the ferritin-mortality association and relative influence of IV iron and inflammation in the USA, where ferritin levels have recently increased dramatically, and in Europe and Japan, where ferritin levels are lower and anemia management practices differ. Methods: Data from 18 261 patients in Phases 4 and 5 (2009-15) of the international Dialysis Outcomes and Practice Patterns Study, a prospective cohort study, were analyzed. Using Cox regression, we modeled the association between baseline ferritin and 1-year mortality with restricted cubic splines and assessed the impact of potential confounders. Results: Median ferritin levels were 718 ng/mL in the USA, 405 in Europe and 83 in Japan. High ferritin levels were associated with elevated mortality (relative to region-specific medians) in all three regions. The strength of this association was attenuated more by adjustment for malnutrition and inflammation than by IV iron and erythropoiesis-stimulating agent dose in each region. Conclusion: The utility of high ferritin as a biomarker for clinical risk due to excess iron stores may be limited, although caution regarding IV iron dosing to higher upper ferritin targets remains warranted. Research to resolve biomarker criteria for iron dosing, and whether optimal anemia management strategies differ internationally, is still needed.

Mortality risk in patients on hemodiafiltration versus hemodialysis: a 'real-world' comparison from the DOPPS.

Background: With its convective component, hemodiafiltration (HDF) provides better middle molecule clearance compared with hemodialysis (HD) and is postulated to improve survival. A previous analysis of Dialysis Outcomes and Practice Patterns Study (DOPPS) data in 1998-2001 found lower mortality rates for high replacement fluid volume HDF versus HD. Randomized controlled trials have not shown uniform survival advantage for HDF; in secondary (non-randomized) analyses, better outcomes were observed in patients receiving the highest convection volumes. Methods: In a 'real-world' setting, we analyzed patients on dialysis >90 days from seven European countries in DOPPS Phases 4 and 5 (2009-15). Adjusted Cox regression was used to study HDF (versus HD) and mortality, overall and by replacement fluid volume. Results: Among 8567 eligible patients, 2012 (23%) were on HDF, ranging from 42% in Sweden to 12% in Germany. Median follow-up was 1.5 years during which 1988 patients died. The adjusted mortality hazard ratio (95% confidence interval) was 1.14 (1.00-1.29) for any HDF versus HD and 1.08 (0.92-1.28) for HDF >20 L replacement fluid volume versus HD. Similar results were found for cardiovascular and infection-related mortality. In an additional analysis aiming to avoid treatment-by-indication bias, we did not observe lower mortality rates in facilities using more HDF (versus HD). Conclusions: Our results do not support the notion that HDF provides superior patient survival. Further trials designed to test the effect of high-volume HDF (versus lower volume HDF versus HD) on clinical outcomes are needed to adequately inform clinical practices.

Mineral and bone disorder management in hemodialysis patients: comparing PTH control practices in Japan with Europe and North America: the Dialysis Outcomes and Practice Patterns Study (DOPPS).

BACKGROUND: High-circulating level of parathyroid hormone (PTH) is associated with elevated mortality in dialysis patients. The Japanese Society for Dialysis Therapy guideline suggests a lower PTH target than other international guidelines; thus, PTH control may differ in Japan compared with other regions, and be associated with mortality. METHODS: We analyzed data from hemodialysis patients with ≥3 measurements of PTH during the first 9 months after enrollment in the Dialysis Outcomes and Practice Patterns Study (DOPPS) phases 4-5 (2009-2015). PTH control was assessed by the mean, slope, and mean squared error (MSE) of all PTH measurements over the 9-month run-in period. Distribution of each PTH control was assessed by regions (Europe/Australia/New Zealand [Eur/ANZ], Japan and North America) and dialysis vintage. Mortality rates were compared across PTH control categories using Cox regression models. RESULTS: Mean PTH was lower in Japan than in other regions across dialysis vintage categories. In patients with dialysis vintage < 90 days, PTH level was more likely to decline > 5% per month in Japan (48% of patients) versus Eur/ANZ (35%) and North America (35%). In patients with dialysis vintage > 1 year, Japanese patients maintained steady PTH, while patients in Eur/ANZ and North America were more likely to experience a PTH increase. Mean PTH was associated with mortality in the overall samples (highest mortality rate for PTH > 600 pg/mL, hazard ratio, 1.35; 95% confidence interval, 1.20 to 1.52 vs PTH 200-399 pg/mL), and the association was obvious in the prevalent patients (hazard ratio, 1.44; 95% confidence interval, 1.26 to 1.65). PTH slope and MSE did not show significant association with mortality in the overall sample as well as in subjects stratified both by region and dialysis vintage. CONCLUSION: PTH control in hemodialysis patients, as measured by keeping a stable PTH level over 9 months, was observed in Japan contrasted with other regions. High PTH mean, but not increased PTH slope and MSE, was associated with mortality especially in prevalent patients.

Unique hemoglobin A1c level distribution and its relationship with mortality in diabetic hemodialysis patients.

Diabetic hemodialysis patients with hemoglobin A1c (HbA1c) levels below 6.5% and over 8.0% face a higher mortality risk. To determine the optimal glycemic control in Japanese patients, we examined the association between HbA1c and mortality in 2,300 Japanese diabetic patients on maintenance hemodialysis with HbA1c levels determined at enrollment in the Japanese Dialysis Outcomes and Practice Patterns Study (JDOPPS) phases 2-5, using Cox regression analysis with adjustment for baseline age, sex, dialysis vintage, 12 general comorbidities, hemoglobin, albumin and creatinine levels, and insulin use; stratification by JDOPPS phase; and facility clustering taken into account. Overall, 54% of patients had HbA1c levels under 6.0, including 14% with HbA1c levels under 5.0. Insulin or oral diabetes medications were used less frequently in patients with higher HbA1c levels. The dependence of mortality on HbA1c level was U shaped. When the group with the lowest mortality (HbA1c 6.0-7.0) was used as a reference, the hazard ratios for HbA1c categories under 5.0, 5.0-6.0, 7.0 to under 8.0, and 8.0 and greater were, respectively, 1.56 (95% confidence interval, 1.05-2.33), 1.26 (0.92-1.71), 1.23 (0.79-1.89), and 2.10 (1.32-3.33) in the adjusted model. The HbA1c level was not associated with self-reported hypoglycemic episodes in JDOPPS phase 5. The HbA1c levels in diabetic hemodialysis patients differ considerably between Japan and those reported from Western countries. Thus, our findings highlight the importance of domestic guidelines for glycemic control by race and country.

Dialysate Potassium, Serum Potassium, Mortality, and Arrhythmia Events in Hemodialysis: Results From the Dialysis Outcomes and Practice Patterns Study (DOPPS).

BACKGROUND: Sudden death is a leading cause of death in patients on maintenance hemodialysis therapy. During hemodialysis sessions, the gradient between serum and dialysate levels results in rapid electrolyte shifts, which may contribute to arrhythmias and sudden death. Controversies exist about the optimal electrolyte concentration in the dialysate; specifically, it is unclear whether patient outcomes differ among those treated with a dialysate potassium concentration of 3 mEq/L compared to 2 mEq/L. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 55,183 patients from 20 countries in the Dialysis Outcomes and Practice Patterns Study (DOPPS) phases 1 to 5 (1996-2015). PREDICTOR: Dialysate potassium concentration at study entry. OUTCOMES: Cox regression was used to estimate the association between dialysate potassium concentration and both all-cause mortality and an arrhythmia composite outcome (arrhythmia-related hospitalization or sudden death), adjusting for potential confounders. RESULTS: During a median follow-up of 16.5 months, 24% of patients died and 7% had an arrhythmia composite outcome. No meaningful difference in clinical outcomes was observed for patients treated with a dialysate potassium concentration of 3 versus 2 mEq/L (adjusted HRs were 0.96 [95% CI, 0.91-1.01] for mortality and 0.98 [95% CI, 0.88-1.08] for arrhythmia composite). Results were similar across predialysis serum potassium levels. As in prior studies, higher serum potassium level was associated with adverse outcomes. However, dialysate potassium concentration had only minimal impact on serum potassium level measured predialysis (+0.09 [95% CI, 0.05-0.14] mEq/L serum potassium per 1 mEq/L greater dialysate potassium concentration). LIMITATIONS: Data were not available for delivered (vs prescribed) dialysate potassium concentration and postdialysis serum potassium level; possible unmeasured confounding. CONCLUSIONS: In combination, these results suggest that approaches other than altering dialysate potassium concentration (eg, education on dietary potassium sources and prescription of potassium-binding medications) may merit further attention to reduce risks associated with high serum potassium levels.

Association between changes in quality of life and mortality in hemodialysis patients: results from the DOPPS.

Background: Cross-sectional health-related quality of life (HR-QOL) measures are associated with mortality in hemodialysis (HD) patients. The impact of changes in HR-QOL on outcomes remains unclear. We describe the association of prior changes in HR-QOL with subsequent mortality among HD patients. Methods: A total of 13 784 patients in the Dialysis Outcomes and Practice Patterns Study had more than one measurement of HR-QOL. The impact of changes between two measurements of the physical (PCS) and mental (MCS) component summary scores of the SF-12 on mortality was estimated with Cox regression. Results: Mean age was 62 years (standard deviation: 14 years); 59% were male and 32% diabetic. Median time between HR-QOL measurements was 12 months [interquartile range (IQR): 11, 14]. Median initial PCS and MCS scores were 37.5 (IQR: 29.4, 46.2) and 46.4 (IQR: 37.2, 54.9); median changes in PCS and MCS scores were -0.2 (IQR: -5.5, 4.7) and -0.1 (IQR: -6.8, 5.9), respectively. The adjusted hazard ratio (HR) for a 5-point decline in HR-QOL score was 1.09 [95% confidence interval (CI): 1.06-1.12] for PCS and 1.05 (95% CI: 1.03-1.08) for MCS. Adjusting for the second QOL score, the change was not associated with mortality: HR = 1.01 (95% CI: 0.98-1.05) for delta PCS and 1.01 (95% CI: 0.98-1.03) for delta MCS. Categorizing the first and second scores as predictors, only the second PCS or MCS score was associated with mortality. Conclusions: In our study, only the most recent HR-QOL score was associated with mortality. Hence, the predictive power of a measurement of HR-QOL is not affected by changes in HR-QOL prior to that measurement; more frequent HR-QOL measurements are needed to improve the prediction of outcomes in HD. Further studies are needed to determine the optimal frequency and appropriate instrument to be used for serial measurements.

Functional Dependence and Mortality in the International Dialysis Outcomes and Practice Patterns Study (DOPPS).

BACKGROUND: Patients receiving long-term dialysis have among the highest mortality and hospitalization rates. In the nonrenal literature, functional dependence is recognized as a contributor to subsequent disability, recurrent hospitalization, and increased mortality. A higher burden of functional dependence with progressive worsening of kidney function has been observed in several studies, suggesting that functional dependence may contribute to both morbidity and mortality in dialysis patients. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 7,226 hemodialysis patients from 12 countries in the DOPPS (Dialysis Outcomes and Practice Patterns Study) phase 4 (2009-2011) with self-reported data for functional status. PREDICTOR: Patients' ability to perform 13 basic and instrumental activities of daily living was summarized to create an overall functional status score (range, 1.25 [most dependent] to 13 [functionally independent]). OUTCOME: Cox regression was used to estimate the association between functional status and all-cause mortality, adjusting for several demographic and clinical risk factors for mortality. Median follow-up was 17.2 months. RESULTS: The proportion of patients who could perform each activity of daily living task without assistance ranged from 97% (eating) to 47% (doing housework). 36% of patients could perform all 13 tasks without assistance (functional status = 13), and 14% of patients had high functional dependence (functional status < 8). Functionally independent patients were younger and had many indicators of better health status, including higher quality of life. Compared with functionally independent patients, the adjusted HR for mortality was 2.37 (95% CI, 1.92-2.94) for patients with functional status < 8. LIMITATIONS: Possible nonresponse bias and residual confounding. CONCLUSIONS: We found a high burden of functional dependence across all age groups and across all DOPPS countries. When adjusting for several known mortality risk factors, including age, access type, cachexia, and multimorbidity, functional dependence was a strong consistent predictor of mortality.