Douglas S. Fuller

Phosphate binder use and mortality among hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS): evaluation of possible confounding by nutritional status.

BACKGROUND Poor nutritional status and both hyper- and hypophosphatemia are associated with increased mortality in maintenance hemodialysis (HD) patients. We assessed associations of phosphate binder prescription with survival and indicators of nutritional status in maintenance HD patients. STUDY DESIGN Prospective cohort study (DOPPS [Dialysis Outcomes and Practice Patterns Study]), 1996-2008. SETTING & PARTICIPANTS 23,898 maintenance HD patients at 923 facilities in 12 countries. PREDICTORS Patient-level phosphate binder prescription and case-mix-adjusted facility percentage of phosphate binder prescription using an instrumental-variable analysis. OUTCOME All-cause mortality. RESULTS Overall, 88% of patients were prescribed phosphate binders. Distributions of age, comorbid conditions, and other characteristics showed small differences between facilities with higher and lower percentages of phosphate binder prescription. Patient-level phosphate binder prescription was associated strongly at baseline with indicators of better nutrition, ie, higher values for serum creatinine, albumin, normalized protein catabolic rate, and body mass index and absence of cachectic appearance. Overall, patients prescribed phosphate binders had 25% lower mortality (HR, 0.75; 95% CI, 0.68-0.83) when adjusted for serum phosphorus level and other covariates; further adjustment for nutritional indicators attenuated this association (HR, 0.88; 95% CI, 0.80-0.97). However, this inverse association was observed for only patients with serum phosphorus levels ≥3.5 mg/dL. In the instrumental-variable analysis, case-mix-adjusted facility percentage of phosphate binder prescription (range, 23%-100%) was associated positively with better nutritional status and inversely with mortality (HR for 10% more phosphate binders, 0.93; 95% CI, 0.89-0.96). Further adjustment for nutritional indicators reduced this association to an HR of 0.95 (95% CI, 0.92-0.99). LIMITATIONS Results were based on phosphate binder prescription; phosphate binder and nutritional data were cross-sectional; dietary restriction was not assessed; observational design limits causal inference due to possible residual confounding. CONCLUSIONS Longer survival and better nutritional status were observed for maintenance HD patients prescribed phosphate binders and in facilities with a greater percentage of phosphate binder prescription. Understanding the mechanisms for explaining this effect and ruling out possible residual confounding require additional research.

Modifiable Practices Associated with Sudden Death among Hemodialysis Patients in the Dialysis Outcomes and Practice Patterns Study

BACKGROUND AND OBJECTIVES Sudden death is common in hemodialysis patients, but whether modifiable practices affect the risk of sudden death remains unclear. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This study analyzed 37,765 participants in 12 countries in the Dialysis Outcomes and Practice Patterns Study to explore the association of the following practices with sudden death (due to cardiac arrhythmia, cardiac arrest, and/or hyperkalemia): treatment time [TT] <210 minutes, Kt/V <1.2, ultrafiltration volume >5.7% of postdialysis weight, low dialysate potassium [K(D) <3]), and prescription of Q wave/T wave interval-prolonging drugs. Cox regression was used to estimate effects on mortality, adjusting for potential confounders. An instrumental variable approach was used to further control for unmeasured patient-level confounding. RESULTS There were 9046 deaths, 26% of which were sudden (crude mortality rate, 15.3/100 patient-years; median follow-up, 1.59 years). Associations with sudden death included hazard ratios of 1.13 for short TT, 1.15 for large ultrafiltration volume, and 1.10 for low Kt/V. Compared with K(D) ≥3 mEq/L, the sudden death rate was higher for K(D) ≤1.5 and K(D)=2-2.5 mEq/L. The instrumental variable approach yielded generally consistent findings. The sudden death rate was elevated for patients taking amiodarone, but not other Q wave/T wave interval-prolonging drugs. CONCLUSIONS This study identified modifiable dialysis practices associated with higher risk of sudden death, including short TT, large ultrafiltration volume, and low K(D). Because K(D) <3 mEq/L is common and easy to change, K(D) tailoring may prevent some sudden deaths. This hypothesis merits testing in clinical trials.

The DOPPS Practice Monitor for US Dialysis Care: Trends Through August 2011

We have examined trends in hemodialysis practice from August 2010 to August 2011, a time frame spanning the implementation of the bundled PPS, a major ESA label change by the FDA, and announcements from CMS on the proposed and final rules for the first year of the Quality Incentive Program (QIP) plus the proposed rules for the second and third years of the QIP. Although many hemodialysis practices have remained stable during this 1-year time period, substantial changes have been seen. These include a decline in epoetin dose and hemoglobin levels, an increase in IV iron use and serum ferritin levels, and an increase in PTH levels. The rates of decline in hemoglobin and epoetin dosing levels were greatest in the 2 months after the ESA label change in June 2011. Trends in anemia care in ensuing months, with more follow-up time after the label change, will be of great interest. In view of declining hemoglobin levels, a mechanism for comprehensive monitoring of transfusion rates is warranted to understand this important aspect of care for hemodialysis patients. Regarding clinical outcomes, no trend in all-cause mortality has been evident during this 1-year time period. Additional follow-up is warranted to understand if findings reported here persist over time, and require confirmation with national data as these become available. Trends in clinical care may not necessarily affect patient outcomes, and careful evaluation is required to understand effects on patient outcomes.

Naturally Occurring Higher Hemoglobin Concentration Does Not Increase Mortality among Hemodialysis Patients

A small percentage of hemodialysis patients maintain higher hemoglobin concentrations without transfusion or erythropoietic therapy. Because uncertainty exists regarding the effects of higher hemoglobin concentration on mortality and quality of life among hemodialysis patients, studying this group of patients with sufficient endogenous erythropoietin may provide additional insights. The prospective, observational Dialysis Outcomes and Practice Patterns Study provides an opportunity to investigate this group. Among 29,796 patients in 12 nations, 545 (1.8%) maintained hemoglobin concentrations >12 g/dl for 4 months without erythropoietic support. This subset tended to be male, to have a longer duration of end-stage renal disease, and to not dialyze via a catheter. Cystic disease as the underlying cause of renal failure was over-represented in this group but was present in only 25%. Lung disease, smoking, and cardiovascular disease were associated with increased likelihood of naturally higher hemoglobin concentration. Quality-of-life scores were not higher among this subset compared with the other patients. Unadjusted mortality risk for patients with hemoglobin >12 g/dl and no erythropoietic therapy was lower than for the other patients, but after thorough adjustment for case mix, there was no difference between groups (relative risk, 0.98; 95% CI 0.80 to 1.19). These data show that naturally occurring hemoglobin concentration >12 g/dl does not associate with increased mortality among hemodialysis patients.

The DOPPS Practice Monitor for US Dialysis Care: Update on Trends in Anemia Management 2 Years Into the Bundle

From Arbor Research Collaborative for Health, Ann Arbor, MI. Originally published online October 21, 2013. Concepts presented in this article are based on data available at the DPM website and may have appeared in resources and media releases distributed by DPM. Address correspondence to Douglas S. Fuller, MS, Arbor Research Collaborative for Health, 340 E Huron St, Ste 300, Ann Arbor, MI 48104. E-mail: doug.fuller@arborresearch.org 2013 by the National Kidney Foundation, Inc. 0272-6386/

Reduced survival and quality of life following return to dialysis after transplant failure: the Dialysis Outcomes and Practice Patterns Study

36.00 http://dx.doi.org/10.1053/j.ajkd.2013.09.006 The Dialysis Outcomes and Practice Patterns Study (DOPPS) Practice Monitor (DPM) was developed to detect and report on trends in dialysis care before, during, and after implementation of the end-stage renal disease prospective payment system (PPS), which was initiated by the US Centers for Medicare & Medicaid Services (CMS) in January 2011. The DPM is based on a national sample of US hemodialysis facilities, with sampling weighting techniques used to calculate nationally representative statistics. The DPM is updated every 4 months at www.dopps.org/DPM, with data available after a lag period of just 2-4 months. The rationale and methods of the DPM have been described previously and statistics based on the DPM sample have been shown to closely correspond to other published national data. As a continuation of previous publications in AJKD, here we highlight trends in anemia from August 2010 through December 2012. As discussed in previous DPM updates, several changes provided direct impetus for US dialysis centers to change anemia management during this period: the addition of previously separate billable services including erythropoiesis-stimulating agents (ESAs) and intravenous (IV) iron to the composite bundled dialysis payment rate, a revised ESA label approved by the US Food and Drug Administration (FDA) that removed a specific target for hemoglobin (Hb) level (June 2011), and soon after, the discontinuation by the CMS Quality Incentive Program of the payment penalty for Hb levels , 10 g/dL. DPM data reported here reflect an average of 3,504 (range, 2,131-4,191) hemodialysis patients in 96 (range, 74-110) facilities per month over a 29-month period. Data are aggregated across facilities and dialysis organizations; thus, aggregated trends may not reflect trends in individual facilities or dialysis organizations.

Facility-level interpatient hemoglobin variability in hemodialysis centers participating in the Dialysis Outcomes and Practice Patterns Study (DOPPS): Associations with mortality, patient characteristics, and facility practices.

BACKGROUND Although dialysis after kidney transplant failure (TF) is common, the outcomes of these patients remain unclear. We compared outcomes of TF patients with transplant-naïve (TN) patients wait-listed for kidney transplantation. METHODS We used data from the Dialysis Outcomes and Practice Patterns Study (DOPPS), including laboratory markers and health-related quality of life (HR-QOL). Mortality and hospitalization of participants with one prior TF versus TN patients were compared using the Cox regression analysis. HR-QOL physical and mental component summary scores (PCS and MCS) were examined using linear mixed models, and clinical practices were compared using logistic regression. RESULTS Compared with TN patients (n = 2806), TF patients (n = 1856) were younger (48 versus 51 years, P = 0.003), less likely to be diabetic (18 versus 27%, P < 0.0001) and to use a permanent surgical vascular access {adjusted odds ratio (AOR): 0.85 [95% confidence interval (CI): 0.70-1.03], P = 0.10}, particularly within the first 3 months after TF [AOR 0.45 (0.32-0.62), P < 0.0001]. TF patients also had lower PCS [mean difference -2.56 (-3.36, -1.75), P < 0.0001] but not MCS [-0.42 (-1.34, 0.50), P = 0.37]. All-cause mortality [adjusted hazard ratio (AHR): 1.32 (95% CI: 1.05-1.66), P = 0.02], especially infection-related [AHR 2.45 (95% CI: 1.36-4.41), P = 0.01], was higher among TF patients. CONCLUSIONS TF patients have reduced QOL and higher mortality, particularly due to infections, than TN patients. Interventions to optimize care before and after starting dialysis remain to be identified and applied in clinical practice.

The Dialysis Outcomes and Practice Patterns Study (DOPPS) Practice Monitor: Rationale and Methods for an Initiative to Monitor the New US Bundled Dialysis Payment System

BACKGROUND Hemodialysis patients with larger hemoglobin level fluctuations have higher mortality rates. We describe facility-level interpatient hemoglobin variability, its relation to patient mortality, and factors associated with facility-level hemoglobin variability or achieving hemoglobin levels of 10.5-12.0 g/dL. Facility-level hemoglobin variability may reflect within-patient hemoglobin variability and facility-level anemia-control practices. STUDY DESIGN Prospective cohort study. SETTING & PARTICIPANTS Data from the Dialysis Outcomes and Practice Patterns Study (DOPPS; 26,510 hemodialysis patients, 930 facilities, 12 countries, 1996-2008) and from the Centers for Medicare & Medicaid Services (CMS; 193,291 hemodialysis patients, 3,741 US facilities, 2002). PREDICTORS Standard deviation (SD) in single-measurement hemoglobin levels in hemodialysis patients in facility cross-sections (facility-level hemoglobin SD); patient characteristics; facility practices. OUTCOMES Patient-level mortality; additionally, facility practices correlated with facility-level hemoglobin SD or patient hemoglobin levels of 10.5-12.0 g/dL. RESULTS Facility-level hemoglobin SD varied more than 5-fold across DOPPS facilities (range, 0.5-2.7 g/dL; mean, 1.3 g/dL) and by country (range, 1.1 in Japan-DOPPS [2005/2006] to 1.7 g/dL in Spain-DOPPS [1998/1999]), with substantial decreases seen in many countries from 1998 to 2007. Facility-level hemoglobin SD was related inversely to patient age, but was associated minimally with more than 30 other patient characteristics and facility mean hemoglobin levels. Several anemia management practices were associated strongly with facility-level hemoglobin SD and having a hemoglobin level of 10.5-12.0 g/dL. When examined in CMS data, facility-level hemoglobin SD was positively associated with within-patient hemoglobin SD during the prior 6 months. Patient mortality rates were higher with greater facility-level hemoglobin SD (DOPPS: HR, 1.08 per 0.5-g/dL greater facility-level hemoglobin SD [95% CI, 1.02-1.15; P = 0.006]; CMS: HR, 1.16 per 0.5-g/dL greater facility-level hemoglobin SD [95% CI, 1.11-1.21; P < 0. 001]). LIMITATIONS Residual confounding. CONCLUSIONS Facility-level hemoglobin SD was associated strongly and positively with patient mortality, not tightly linked to numerous patient characteristics, but related strongly to facility anemia management practices. Facility-level hemoglobin variability may be modifiable and its optimization may improve hemodialysis patient survival.

Pruritus in hemodialysis patients: Results from the Japanese Dialysis Outcomes and Practice Patterns Study (JDOPPS)

A new initiative of the US Dialysis Outcomes and Practice Patterns Study (DOPPS), the DOPPS Practice Monitor (DPM), provides up-to-date data and analyses to monitor trends in dialysis practice during implementation of the new Centers for Medicare & Medicaid Services (CMS) end-stage renal disease Prospective Payment System (PPS; 2011-2014). We review DPM rationale, design, sampling approach, analytic methods, and facility sample characteristics. Using stratified random sampling, the sample of ~145 US facilities provides results representative nationally and by facility type (dialysis organization size, rural/urban, free standing/hospital based), achieving coverage similar to the CMS sample frame at average values and tails of the distributions for key measures and patient characteristics. A publicly available web report (www.dopps.org/DPM) provides detailed trends, including demographic, comorbidity, and dialysis data; medications; vascular access; and quality of life. Findings are updated every 4 months with a lag of only 3-4 months. Baseline data are from mid-2010, before the new PPS. In sum, the DPM provides timely representative data to monitor effects of the expanded PPS on dialysis practice. Findings can serve as an early warning system for possible adverse effects on clinical care and as a basis for community outreach, editorial comment, and informed advocacy.

The DOPPS Practice Monitor for US Dialysis Care: Potential Impact of Recent Guidelines and Regulatory Changes on Management of Mineral and Bone Disorder Among US Hemodialysis Patients

Pruritus affects many patients undergoing hemodialysis (HD). In this study, pruritus and its relationship to morbidity, quality of life (QoL), sleep quality, and patient laboratory measures were analyzed in a large sample of Japanese patients undergoing HD. Severity of patient‐reported pruritus symptoms experienced during a 4‐week period was collected from 6480 Japanese patients undergoing HD in three phases of the Dialysis Outcomes and Practice Patterns Study (DOPPS; 1996–2008; 60–65 study facilities/phase). Adjusted linear and logistic regressions were used to identify associations of pruritus with treatment parameters and QoL outcomes. Adjusted Cox regressions examined the influence of pruritus severity on mortality. Moderate to extreme pruritus was experienced by 44% of prevalent patients undergoing HD in the Japanese Dialysis Outcomes and Practice Patterns Study. Many patient characteristics were significantly associated with pruritus, but this did not explain the large differences in pruritus among facilities (20–70%). Pruritus was slightly less common in patients starting HD than in patients on dialysis >1 year. Patients with moderate to extreme pruritus were more likely to feel drained (adjusted odds ratio = 2.2–5.8, P < 0.0001), have poor sleep quality (adjusted odds ratio = 1.9–3.7, P < 0.0001), and have QoL mental and physical composite scores 2.3–6.7 points lower (P < 0.0001) than patients with no/mild pruritus. Pruritus in patients undergoing HD was associated with a 23% higher mortality risk (P = 0.09). The many poor outcomes associated with pruritus underscore the need for better therapeutic agents to provide relief for the 40–50% of prevalent patients undergoing HD substantially affected by pruritus. Pruritus in new patients with end‐stage renal disease likely results from uremia or pre‐existing conditions (not HD per se), indicating the need to understand development of pruritus before end‐stage renal disease.