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Rationale & Objective: Missed hemodialysis (HD) treatments not due to hospitalization have been associated with poor clinical outcomes and related in part to treatment nonadherence. Using data from the Dialysis Outcomes and Practice Patterns Study (DOPPS) phase 5 (2012-2015), we report findings from an international investigation of missed treatments among patients prescribed thrice-weekly HD., Study Design: Prospective observational study., Setting & Participants: 8,501 patients participating in DOPPS, on HD therapy for more than 120 days, from 20 countries. Longitudinal and cross-sectional analyses were performed based on the 4,493 patients from countries in which 4-month missed treatment risk was > 5%., Predictors: The main predictor of patient outcomes was 1 or more missed treatments in the 4 months before DOPPS phase 5 enrollment; predictors of missed treatments included country, patient characteristics, and clinical factors., Outcomes: Mortality, hospitalization, laboratory measures, patient-reported outcomes, and 4-month missed treatment risk., Analytical Approach: Outcomes were assessed using Cox proportional hazards, logistic, and linear regression, adjusting for case-mix and country., Results: The 4-month missed treatment risk varied more than 50-fold across all 20 DOPPS countries, ranging from < 1% in Italy and Japan to 24% in the United States. Missed treatments were more likely with younger age, less time on dialysis therapy, shorter HD treatment time, lower Kt/V, longer travel time to HD centers, and more symptoms of depression. Missed treatments were positively associated with all-cause mortality (HR, 1.68; 95% CI, 1.37-2.05), cardiovascular mortality, sudden death/cardiac arrest, hospitalization, serum phosphorus level > 5.5mg/dL, parathyroid hormone level > 300pg/mL, hemoglobin level < 10g/dL, higher kidney disease burden, and worse general and mental health., Limitations: Possible residual confounding; temporal ambiguity in the cross-sectional analyses., Conclusions: In the countries with a 4-month missed treatment risk > 5%, HD patients were more likely to die, be hospitalized, and have poorer patient-reported outcomes and laboratory measures when 1 or more missed treatments occurred in a 4-month period. The large variation in missed treatments across 20 nations suggests that their occurrence is potentially modifiable, especially in the United States and other countries in which missed treatment risk is high., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Anemia management changed substantially among dialysis patients in the United States around the time of implementation of the new Centers for Medicare & Medicaid Services bundled payment system and erythropoiesis-stimulating agent (ESA) label change in 2011. Among these, average ferritin levels increased dramatically and have remained high since; this study sought to gain understanding of this sustained rise in ferritin levels., Design, Setting, Participants, & Measurements: Trends in mean ferritin, hemoglobin, IV iron dose, and ESA dose from 2009 to 2013 were examined in 9735 patients from 91 United States Dialysis Outcomes and Practice Patterns Study facilities. Linear mixed models were used to assess the extent to which intravenous (IV) iron and ESA dose accounted for patients' changes in ferritin over time., Results: Mean ESA dose and hemoglobin levels declined throughout the study. Mean IV iron dose increased from 210 mg/mo in 2009-2010 to a peak of 280 mg/mo in 2011, then declined back to 200 mg/mo and remained stable from 2012 to 2013. Mean ferritin increased from 601 ng/ml in the third quarter of 2009 to 887 ng/ml in the first quarter of 2012; models suggest that higher IV iron dosing was a primary determinant during 2011, but lower ESA doses contributed to the sustained high ferritin levels thereafter. In a subset of 17 facilities that decreased IV iron dose in 2011, mean ferritin rose by 120 ng/ml to 764 ng/ml, which appeared to be primarily due to ESA reduction. Together, changes in IV iron and ESA doses accounted for 46% of the increase in ferritin over the study period., Conclusions: In contrast to expectations, the rise in average IV iron dose did not persist beyond 2011. The sustained rise in ferritin levels in United States dialysis patients after policy changes in 2011, to average levels well in excess of 800 ng/ml, appeared to be partly due to reductions in ESA dosing and not solely IV iron dosing practices. The effect of these changes in ferritin on health outcomes requires further investigation., (Copyright © 2015 by the American Society of Nephrology.)

Most patients with end-stage renal disease depend on intermittent hemodialysis to maintain levels of serum potassium and other electrolytes within a normal range. However, one of the challenges has been the safety of using a low-potassium dialysate to achieve that goal, given the concern about the effects that rapid and/or large changes in serum potassium concentrations may have on cardiac electrophysiology and arrhythmia. Additionally, in this patient population, there is a high prevalence of structural cardiac changes and ischemic heart disease, making them even more susceptible to acute arrhythmogenic triggers. This concern is highlighted by the knowledge that about two-thirds of all cardiac deaths in dialysis are due to sudden cardiac death and that sudden cardiac death accounts for 25% of the overall death for end-stage renal disease. Developing new approaches and practice standards for potassium removal during dialysis, as well as understanding other modifiable triggers of sudden cardiac death, such as other electrolyte components of the dialysate (magnesium and calcium), rapid ultrafiltration rates, and safety of a number of medications (ie, drugs that prolong the QT interval or use of digoxin), are critical in order to decrease the unacceptably high cardiac mortality experienced by hemodialysis-dependent patients., (Published by Elsevier Inc.)

We reviewed a number of prospective randomized and multiple retrospective cohort studies of different dialysis prescriptions: longer dialysis time, at a frequency of at least three times a week, or a frequency of daily hemodialysis with a shorter dialysis time. Interestingly, the retrospective analyses have generally found significant survival benefits in the intensive dialysis groups, whereas more modest effects were observed in the prospective randomized controlled trials. The reason for this discrepancy may be related to the retrospective nature of the studies and possible selection bias; for example, the patients who were prescribed more frequent dialysis may have had more difficulties with volume control or high blood pressure. In contrast, the randomized controlled trials of increased dialysis frequency, which have shown indirect and modest benefits in complex coprimary end points, have small sample sizes and are plagued with difficulties in recruitment and compliance with the randomly allocated more frequent dialysis. This review, which attempts to balance the potential benefits of more frequent dialysis with the burden on the patient's lifestyle, an increased risk of access malfunction, as well as societal costs of such intensive dialysis prescriptions, concludes in favor of the conventional three times per week dialysis (at a minimum) but at longer dialysis times than is currently prescribed based on the Kt/Vurea metric alone.

African Americans require higher doses of erythropoiesis-stimulating agents (ESAs) during dialysis to manage anemia, but the influence of sickle cell trait and other hemoglobinopathy traits on anemia in dialysis patients has not been adequately evaluated. We performed a cross-sectional study of a large cohort of adult African-American hemodialysis patients in the United States to determine the prevalence of hemoglobinopathy traits and quantify their influence on ESA dosing. Laboratory and clinical data were obtained over 6 months in 2011. Among 5319 African-American patients, 542 (10.2%) patients had sickle cell trait, and 129 (2.4%) patients had hemoglobin C trait; no other hemoglobinopathy traits were present. Sickle cell trait was more common in this cohort than the general African-American population (10.2% versus 6.5%-8.7%, respectively, P<0.05). Among 5002 patients (10.3% sickle cell trait and 2.4% hemoglobin C trait) receiving ESAs, demographic and clinical variables were similar across groups, with achieved hemoglobin levels being nearly identical. Patients with hemoglobinopathy traits received higher median doses of ESA than patients with normal hemoglobin (4737.4 versus 4364.1 units/treatment, respectively, P=0.02). In multivariable analyses, hemoglobinopathy traits associated with 13.2% more ESA per treatment (P=0.001). Within subgroups, sickle cell trait patients received 13.2% (P=0.003) higher dose and hemoglobin C trait patients exhibited a similar difference (12.9%, P=0.12). Sensitivity analyses using weight-based dosing definitions and separate logistic regression models showed comparable associations. Our findings suggest that the presence of sickle cell trait and hemoglobin C trait may explain, at least in part, prior observations of greater ESA doses administered to African-American dialysis patients relative to Caucasian patients.

Mortality rates for maintenance hemodialysis patients are much higher than the general population and are even greater soon after starting dialysis. Here we analyzed mortality patterns in 86,886 patients in 11 countries focusing on the early dialysis period using data from the Dialysis Outcomes and Practice Patterns Study, a prospective cohort study of in-center hemodialysis. The primary outcome was all-cause mortality, using time-dependent Cox regression, stratified by study phase adjusted for age, sex, race, and diabetes. The main predictor was time since dialysis start as divided into early (up to 120 days), intermediate (121-365 days), and late (over 365 days) periods. Mortality rates (deaths/100 patient-years) were 26.7 (95% confidence intervals 25.6-27.9), 16.9 (16.2-17.6), and 13.7 (13.5-14.0) in the early, intermediate, and late periods, respectively. In each country, mortality was higher in the early compared to the intermediate period, with a range of adjusted mortality ratios from 3.10 (2.22-4.32) in Japan to 1.15 (0.87-1.53) in the United Kingdom. Adjusted mortality rates were similar for intermediate and late periods. The ratio of elevated mortality rates in the early to the intermediate period increased with age. Within each period, mortality was higher in the United States than in most other countries. Thus, internationally, the early hemodialysis period is a high-risk time for all countries studied, with substantial differences in mortality between countries. Efforts to improve outcomes should focus on the transition period and the first few months of dialysis.

Purpose of Review: This review examines recent advances in understanding of how clinical outcomes for hemodialysis patients may be improved by achieving longer or more frequent treatment times, lower ultrafiltration rates (UFRs), improving nutritional status, and individualizing dialysate composition. This review also discusses the controversy related to timing of dialysis initiation., Recent Findings: Many observational studies and several randomized controlled trials indicate longer dialysis treatment times, particularly nocturnal dialysis, and/or more frequent dialysis improve morbidity and mortality. Recent evidence also suggests that lower UFR and more consistent achievement of 'dry weight' may help minimize the damage from myocardial stunning and chronic volume overload that occurs in the majority of patients who receive conventional hemodialysis during the day with a standard schedule of 3-5 h, 3 times a week. Other aspects of the dialysis procedure such as appropriate estimated glomerular filtration rate for dialysis initiation and individualizing dialysate composition may also minimize cardiovascular risk. Finally, several studies have highlighted the benefits of oral nutritional supplementation (ONS) during dialysis., Summary: Greater treatment times per week with slower UFR, consistent attainment of 'dry weight', individualized dialysate prescriptions, and administration of ONS to malnourished patients are likely to reduce hospitalizations and improve survival in this high-risk population of end-stage renal disease patients.

Morbidity, hospitalizations, and costs for the treatment of individuals with end-stage renal disease are simply not improving at a rate that is acceptable to many physicians and dialysis providers in the United States. Various conferences and papers have suggested what processes need to become part of the dialysis prescription to accelerate change. Controlling cardiovascular disease is a part of that change, and controlling extra-cellular volume (ECV) is necessary to accomplish this. Three dialysis providers joined in a quality initiative to objectively assess the ultrafiltration process and measure "normalized" ECV, with the outcome objective to decrease ECV-related hospitalizations. The results show a decrease in ECV-related hospitalizations by 50%. The model of dialysis prescription needs to now change to Kt/V + objective ECV control.

Background: Hemodialysis (HD) access is considered a critical and actionable determinant of morbidity, with a growing literature suggesting that initial HD access type is an important marker of long-term outcomes. Accordingly, we examined HD access during the incident dialysis period, focusing on infection risk and successful fistula creation during the first dialysis year., Study Design: Longitudinal cohort., Setting & Participants: All US adults admitted to Fresenius Medical Care North America facilities within 15 days of first maintenance dialysis session between January 1 and December 31, 2007., Predictor: Vascular access type at HD therapy initiation., Outcomes: Vascular access type at 90 days and at the end of the first year on HD therapy, bloodstream infection within the first year by access type, and catheter complication rate., Results: Of 25,003 incident dialysis patients studied, 19,622 (78.5%) initiated dialysis with a catheter; 4,151 (16.6%), with a fistula; and 1,230 (4.9%), with a graft. At 90 days, 14,105 (69.7%) had a catheter, 4,432 (21.9%) had a fistula, and 1,705 (8.4%) had a graft. Functioning fistulas and grafts at dialysis therapy initiation had first-year failure rates of 10% and 15%, respectively. Grafts were seldom replaced by fistulas (3%), whereas 7,064 (47.6%) of all patients who initiated with a catheter alone still had only a catheter at 1 year. Overall, 3,327 (13.3%) patients had at least one positive blood culture during follow-up, with the risk being similar between the fistula and graft groups, but approximately 3-fold higher in patients with a catheter (P<0.001 for either comparison). Nearly 1 in 3 catheters (32.5%) will require tissue plasminogen activator use by a median of 41 days, with 59% requiring more than one tissue plasminogen activator administration., Limitations: Potential underestimation of bacteremia because follow-up blood culture results did not include samples sent to local laboratories., Conclusions: In a large and representative population of incident US dialysis patients, catheter use remains very high during the first year of HD care and is associated with high mechanical complication and bloodstream infection rates., (Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The relationship between severity of depressive symptoms reported by incident dialysis patients and first-year outcomes is not known., Methods: We evaluated the association between self-report of depressive symptoms in incident hemodialysis patients admitted at Fresenius Medical Care North America facilities between 1 January and 31 December 2006 and mortality or withdrawal from dialysis for up to 1 year after the initial survey. The impact of depression scores calculated from two Short Form-36 (SF-36) questionnaires was determined independently of the mental and physical component scores, case-mix and laboratory variables using stepwise Cox models., Results: We received 6415 SF-36 responses within 46±24 days of first dialysis from a cohort with a mean age of 62.3±15.2 years; 58% were diabetic, 45% were female and 69% were Caucasian. A 1-point increase in depression score was associated with unadjusted hazard ratio (HR) of 1.09 (1.03, 1.15) for mortality and 1.15 (1.05, 1.26) for withdrawal from dialysis. After adjustment, a 1-point increase in depression score had a mortality HR of 1.08 (1.01, 1.14) and for withdrawal 1.19 (1.08, 1.31)., Conclusions: Depressive symptoms reported within the first 90 days of dialysis were associated with greater dialysis withdrawal and mortality risk over the succeeding year. Whether further evaluation for and treatment of depression during this early vulnerable period may improve symptoms, increase survival and decrease premature withdrawal from dialysis requires confirmation in prospective clinical trials.

A previous commentary pointed out that the renal community has led American healthcare in the development and continuous improvement of quality outcomes. However, survival, hospitalization, and quality of life for US dialysis patients is still not optimal. This follow-up commentary examines the obstacles, gaps, and metrics that characterize this unfortunate state of affairs. It posits that current paradigms are essential contributors to quality outcomes but are no longer sufficient to improve quality. New strategies are needed that arise from a preponderance of evidence, in addition to beyond a reasonable doubt standard. This work offers an action plan that consists of new pathways of care that will lead to improved survival, fewer hospitalizations and rehospitalizations, and better quality of life for patients undergoing dialysis therapy. Nephrologists in collaboration with large and small dialysis organizations and other stakeholders, including the Centers for Medicare and Medicaid Services, can implement these proposed new pathways of care and closely monitor their effectiveness. We suggest that our patients deserve nothing less and must receive even more.

Whether the duration of hemodialysis treatments improves outcomes remains controversial. Here, we evaluated survival and clinical changes associated with converting from conventional hemodialysis (mean=3.75 h/treatment) to in-center nocturnal hemodialysis (mean=7.85 h/treatment). All 959 consecutive patients who initiated nocturnal hemodialysis for the first time in 77 Fresenius Medical Care facilities during 2006 and 2007 were eligible. We used Cox models to compare risk for mortality during 2 years of follow-up in a 1:3 propensity score-matched cohort of 746 nocturnal and 2062 control patients on conventional hemodialysis. Two-year mortality was 19% among nocturnal hemodialysis patients compared with 27% among conventional patients. Nocturnal hemodialysis associated with a 25% reduction in the risk for death after adjustment for age, body mass index, and dialysis vintage (hazard ratio=0.75, 95% confidence interval=0.61-0.91, P=0.004). With respect to clinical features, interdialytic weight gain, albumin, hemoglobin, dialysis dose, and calcium increased on nocturnal therapy, whereas postdialysis weight, predialysis systolic blood pressure, ultrafiltration rate, phosphorus, and white blood cell count declined (all P<0.001). In summary, notwithstanding the possibility of residual selection bias, conversion to treatment with nocturnal hemodialysis associates with favorable clinical features, laboratory biomarkers, and improved survival compared with propensity score-matched controls. The potential impact of extended treatment time on clinical outcomes while maintaining a three times per week hemodialysis schedule requires evaluation in future clinical trials.

The rate of rehospitalization is at a critical level. Twenty percent of all Medicare patients are rehospitalized within 30 days of discharge, and this rate is even higher (36%) for end-stage renal disease patients. Dialysis-dependent patients are commonly discharged from the hospital with a decline in various health measures (such as hemoglobin, albumin, and estimated dry weight) when compared to pre-hospital values, making the common response to resume previous orders" in the outpatient setting inadequate. Both quality of care and financial penalties by the Centers for Medicare & Medicaid Services have set the stage for partnerships between dialysis providers and hospitals to develop strategies to reduce readmissions for ESRD patients, and provide for the "RightReturn" to the outpatient setting with resumption of their daily lives at home in optimal health.

Background and Objectives: Approximately one million Americans initiated chronic dialysis over the past decade; the first-year mortality rate reported by the U.S. Renal Data System was 19.6% in 2007. This estimate has historically excluded the first 90 days of chronic dialysis., Design, Setting, Participants, & Measurements: To characterize the mortality and hospitalization risks for patients starting chronic renal replacement therapy, we followed all patients initiating dialysis in 1733 facilities throughout the United States (n = 303,289). Mortality and hospitalizations within the first 90 days were compared with outcomes after this period, and the results were analyzed. Standard time-series analyses were used to depict the weekly risk estimates for each outcome., Results: Between 1997 and 2009, >300,000 patients initiated chronic dialysis and were followed for >35 million dialysis treatments; the highest risk for morbidity and mortality occurred in the first 2 weeks of treatment. The initial 2-week risk of death for a typical dialysis patient was 2.72-fold higher, and the risk of hospitalization was 1.95-fold higher when compared to a patient who survived the first year of chronic dialysis (week 53 after initiation). Similarly, over the first 90 days, the risk of mortality and hospitalization remained elevated. Thereafter, between days 91 and 365, these risks decreased considerably by more than half. Surviving these first weeks of dialysis was most associated with the type of vascular access. Initiating dialysis with a fistula was associated with a decreased early death risk by 61%, whereas peritoneal dialysis decreased the risk by 87%., Conclusions: The first 2 weeks of chronic dialysis are associated with heightened mortality and hospitalization risks, which remain elevated over the ensuing 90 days.

To compare the relative effectiveness of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in reducing cardiovascular mortality in chronic hemodialysis patients, we conducted an observational analysis of all patients initiated on ACEI or ARB therapy undergoing chronic hemodialysis at a large dialysis provider. Survival curves with mortality hazard ratios (HRs) were generated using the Kaplan-Meier method and Cox regression. Outcomes were compared using inverse probability of treatment weighting and propensity score matching. Over 6 years, 22,800 patients were newly initiated on an ACEI and 5828 on an ARB after at least 60 days of chronic hemodialysis. After adjustment for baseline cardiovascular risk factors, there was no significant difference in the risk of cardiovascular, all-cause, or cerebrovascular mortality in patients initiated on an ARB compared with an ACEI (HR of 0.96). A third of 28,628 patients, newly started on an ACEI or ARB, went on to another antihypertensive medication in succession. After adjustment for risk factors, 701 patients initiated on combined ACEI and ARB therapy (HR of 1.45) or 6866 patients on ACEI and non-ARB antihypertensive agent (HR of 1.27) were at increased risk of cardiovascular death compared with 1758 patients initiated on an ARB and non-ACEI antihypertensive therapy. Thus, an ARB, in combination with another antihypertensive medication (but not an ACEI), may have a beneficial effect on cardiovascular mortality. As observational studies may be confounded by indication, even when adjusted, randomized clinical trials are needed to confirm these findings.

Background and Objectives: Referring hemodialysis patients for elective access angiography and percutaneous transluminal angioplasty (PTA) is commonly done to prevent access failure, yet the effectiveness of this procedure remains unclear. DESIGN, SETTING, PARTICIPANTS, & MEASURES: An observational matched cohort analysis among 40,132 Medicare beneficiaries receiving hemodialysis with a fistula or graft was performed. Cox regression was used to determine whether access intervention was associated with improved 1-year access survival., Results: Nonsurgical access intervention was found to be frequent at a rate of 20.9 procedures per 100 access years. In the 1-year period after intervention using angiography and PTA, the overall access failure rate was 53.7 per 100 access years in the intervention group and 49.6 in the nonintervention group (HR = 1.02; 95% CI, 0.96 to 1.08). Similar findings were also seen when the analysis was repeated in only fistulas (HR = 1.06; 95% CI, 0.98 to 1.15) and grafts (HR = 0.95; 95% CI, 0.86 to 1.05). In patients with a low intra-access flow rate (HR = 0.86; 95% CI, 0.75 to 0.99) or a new access (HR = 0.79; 95% CI, 0.71 to 0.89), angiography and PTA significantly increased access survival when compared with nonintervention (P for interaction was <0.0001). Angiography-PTA-related upper-extremity hematoma, vessel injury, or embolism-thrombosis occurred in 1.1% of all patients., Conclusions: Access characteristics significantly modify the survival benefits of angiography and PTA intervention where the benefits of these interventions are most seen in newer accesses or accesses with insufficient flow.

Background: Patients' education about transplant, hemodialysis (HD), peritoneal dialysis (PD), and conservative care often is provided by nephrologists as needed and occurs as time allows., Study Design: Quality improvement report., Setting & Participants: Attendees of a national treatment options program (TOPs) who initiated long-term dialysis therapy (median, 3.4 months) at Fresenius Medical Care, North America facilities throughout 2008 were compared with period-prevalent incident patients receiving usual care., Quality Improvement Plan: Standardized predialysis treatment options education., Outcomes: Rates of opting for PD modality, arteriovenous HD access at initiation, and early (90-day) mortality risk., Measurements: Logistic regression (for choice of PD and HD access type) and Cox models (for early mortality) were constructed, including a 1:1 matched cohort. A post hoc sensitivity analysis also compared a propensity score-matched cohort., Results: 3,165 TOPs attendees (10.5% of 30,217 incident patients admitted between January 1 and December 31, 2008), were younger, more likely to be white, and had slightly larger body surface area. The unadjusted OR for TOPs attendees for selecting PD therapy was 8.45 (95% CI, 7.63-9.37) with a case-mix plus laboratory-adjusted OR of 5.13 (95% CI, 3.58-7.35). For patients who opted for in-center HD therapy, the OR was 2.14 (95% CI, 1.96-2.33) and adjusted OR was 2.06 (95% CI, 1.88-2.26) for starting with a fistula or graft. The unadjusted early mortality HR was 0.51 (95% CI, 0.43-0.60) and case-mix plus laboratory-adjusted adjusted HR was 0.61 (95% CI, 0.50-0.74) for TOPs attendees (all outcomes, P < 0.001). These results were consistent in the 1:1 matched analysis and propensity score-matched analysis., Limitations: It is possible that physicians who referred to these programs were more likely to prescribe PD therapy or place arteriovenous accesses. Motivated, treatment-adherent patients (who would have better outcomes) may have self-selected to attend education sessions., Conclusion: Attending an options class predialysis was associated with more frequent selection of home dialysis, fewer tunneled HD catheters, and lower mortality risk during the first 90 days of dialysis therapy., (Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

The ability to offer repetitive hemodialysis for treatment of chronic kidney failure has now reached its half-century anniversary. Although millions of patients have benefited from this life-extending procedure, current results in the United States have now stagnated with only small annual improvements in survival and continued high hospitalization rates. Recognition that this stagnation may be, at least in part, the result of inadequacies of current and prior paths utilized in dialysis treatment has led to the concept that dialysis therapy is at a crossroads and that new paths need to be articulated, explored, and applied. This article proposes some of these new paths and their rationale. Two elements of the new paths are emphasized: avoidance of indwelling catheters for vascular access and meticulous attention to control of extracellular volume and mitigation of left ventricular hypertrophy and fibrosis. It is postulated that progress in these two areas, along with continued attention to other elements embodied in the new and old paths, will unlock the stagnation in outcomes of dialysis therapy of end-stage kidney failure and allow it to realize its full potential of prolonging life and alleviating disability.

Background and Objectives: Higher mortality risk reported with reuse versus single use of dialyzers is potentially related to reuse reagents that modify membrane surface characteristics and the blood-membrane interface. A key mechanism may involve stimulation of an inflammatory response., Design, Setting, Participants, & Measurements: In a prospective crossover design, laboratory markers and mortality from 23 hemodialysis facilities abandoning reuse with peracetic acid mixture were tracked. C-reactive protein (CRP), white blood cell (WBC) count, albumin, and prealbumin were measured for 2 consecutive months before abandoning reuse and subsequently within 3 and 6 months on single use. Survival models were utilized to compare the 6-month period before abandoning reuse (baseline) and the 6-month period on single use of dialyzers after a 3-month "washout period.", Results: Patients from baseline and single-use periods had a mean age of approximately 63 years; 44% were female, 54% were diabetic, 60% were white, and the mean vintage was approximately 3.2 years. The unadjusted hazard ratio for death was 0.70 and after case-mix adjustment was 0.74 for single use compared with reuse. Patients with CRP≥5 mg/L during reuse (mean CRP=26.6 mg/ml in April) declined on single use to 20.2 mg/L by August and 20.4 mg/L by November. WBC count declined slightly during single use, but nutritional markers were unchanged., Conclusions: Abandonment of peracetic-acid-based reuse was associated with improved survival and lower levels of inflammatory but not nutritional markers. Further study is needed to evaluate a potential link between dialyzer reuse, inflammation, and mortality.

The International Quotidian Dialysis Registry (IQDR) is a global initiative designed to study practices and outcomes associated with the use of hemodialysis (HD) regimens of increased frequency and/or duration. The IQDR grew out of the initiative that lead to the randomized prospective studies of nocturnal HD and short hours daily dialysis vs. conventional thrice weekly HD that are conducted by the Frequent Hemodialysis Network sponsored by the National Institutes of Health. These 2 separate studies are drawing to a close and the first results are expected to be reported later this year. These studies use surrogate outcomes for their primary endpoints as they are not powered to look at outcomes of mortality and hospitalization. The IQDR attempts to aggregate long-term follow-up data from centers utilizing alternative HD regimens worldwide and will have adequate statistical power to examine those important outcomes. To date, the IQDR has enrolled patients from Canada, the United States, Australia, New Zealand, and France and has linked with commercial databases and national registries. This sixth annual report of the IQDR describes: (1) An update on the governance structure; (2) The recommendations made at the first general meetings of the IQDR Scientific Committee and Advisory Board; (3) The status of those recommendations; (4) A summary of current data sources and participating registries; (5) The status of recruitment to date; (6) The creation of a specific Canadian IQDR data set and; (7) The current research agenda., (© 2011 The Authors. Hemodialysis International © 2011 International Society for Hemodialysis.)

Background and Objectives: Conversion from central venous catheters to a graft or a fistula is associated with lower mortality risk in long-term hemodialysis (HD) patients; however, a similar association with hospitalization risk remains to be elucidated., Design, Setting, Participants, & Measurements: We conducted a prospective observational study all maintenance in-center HD patients who were treated in Fresenius Medical Care, North America legacy facilities; were alive on January 1, 2007; and had baseline laboratory data from December 2006. Access conversion (particularly from a catheter to a fistula or a graft) during the 4-month period from January 1 through April 30, 2007, was linked using Cox models to hospitalization risk during the succeeding 1-year follow-up period (until April 30, 2008)., Results: The cohort (N = 79,545) on January 1, 2007 had 43% fistulas, 29% catheters, and 27% grafts. By April 30, 2007, 70,852 patients were still on HD, and among 19,792 catheters initially, only 10.3% (2045 patients) converted to either a graft or a fistula. With catheters as reference, patients who converted to grafts/fistulas had similar adjusted hazard ratios (0.69) as patients on fistulas (0.71), while patients with fistulas/grafts who converted to catheters did worse (1.22), all P < 0.0001., Conclusions: Catheters remain associated with the greatest hospitalization risk. Conversion from a catheter to either graft or fistula had significantly lower hospitalization risk relative to keeping the catheter. Prospective studies are needed to determine whether programs that reduce catheters will decrease hospitalization risk in HD patients.

Background and Objectives: The benefits and risks of aggressive glycemic control in diabetes mellitus complicated by end-stage kidney failure remain uncertain but have importance because of the large patient population with inferior overall prognosis. Recent large observational studies with differing methodologies reached somewhat contrasting conclusions regarding the association of hemoglobin A1c with survival in diabetic chronic hemodialysis patients., Design, Setting, Participants, & Measurements: This study supplements the authors' previous analysis (which found no correlation) by extending the follow-up period to 3 years and using time-dependent survival models with repeated measures. Among 24,875 nationally distributed study patients, 94.5% had type 2 diabetes, allowing additional analysis in the subset with type 1 diabetes. Data were collected at baseline and every quarter to a maximum of 3 years' follow-up., Results: Adjusted standard and time-dependent Cox models indicated that only extremes of glycemia were associated with inferior survival. There was no effect modification by serum albumin levels, a marker of protein nutrition status, and no trend associated with random glucose measurements in a post hoc analysis. In type 1 diabetic patients, upper extreme hemoglobin A1c values indicated lower survival risk., Conclusions: Sustained extremes of glycemia were only variably and weakly associated with decreased survival in this population. In the absence of randomized, controlled trials, these results suggest that aggressive glycemic control cannot be routinely recommended for all diabetic hemodialysis patients on the basis of reducing mortality risk. Physicians are encouraged to individualize glycemic targets based on potential risks and benefits in diabetic ESRD patients.

Background and Objectives: Randomized, controlled trials (RCTs) are the gold standard for defining causal inferences but are sometimes not feasible because of cost, ethical, or time considerations. We explored the accuracy and potential use of a "simulated trial" through the modeling of a previously published RCT, Die Deutsche Diabetes Dialyse Studie (4D Study), a landmark study that investigated the cardiovascular benefit of atorvastatin use in 1255 patients with ESRD., Design, Setting, Participants, & Measurements: Using a large historical database of interventions and outcomes in dialysis patients, we conducted an observational model of the 4D Study in dialysis patients who had type 2 diabetes and were prescribed a statin (5144 patients) and matched to a non-statin user (5144 control subjects) before multivariate modeling. Inclusion, exclusion, and outcome parameters of the study, as prespecified by the 4D Study, were strictly modeled in this analysis., Results: In covariate- and propensity-adjusted Cox regression, statin use (versus nonuse) was associated with a decrease in the composite primary outcome of cardiac death, nonfatal myocardial infarction, and stroke. Statin use was also associated with a decrease in cardiovascular mortality and all cardiac events combined. The hazard ratios in this observational model were numerically comparable to the hazard ratios reported in the 4D Study; however, because of the larger number of patients "enrolled," results in this simulated study achieved statistical significance., Conclusions: Statin use was associated with some cardiovascular benefit in a simulated trial of patients with ESRD; however, the size of benefit was considerably smaller than that seen in the general population. Such simulated trials may represent an exploratory, cost-effective option when RCTs are not immediately feasible.

Background and Objectives: The Short Form 12 (SF-12) has not been validated for long-term dialysis patients. The study compared physical and mental component summary (PCS/MCS) scores from the SF-36 with those from the embedded SF-12 in a national cohort of dialysis patients., Design, Setting, Participants, & Measurements: All 44,395 patients who had scorable SF-36 and SF-12 from January 1, 2006, to December 31, 2006, and were treated at Fresenius Medical Care, North America facilities were included. Death and first hospitalization were followed for up to 1 year from the date of survey. Correlation and agreement were obtained between PCS-36 and PCS-12 and MCS-36 and MCS-12; then Cox models were constructed to compare associated hazard ratios (HRs) between them., Results: Physical and mental dimensions both exhibited excellent intraclass correlation coefficients of 0.94. Each incremental point for both PCS-12 and PCS-36 was associated with a 2.4% lower adjusted HR of death and 0.4% decline in HR for first hospitalization (both P < 0.0001). Corresponding improvement in HR of death for each MCS point was 1.2% for MCS-12 and 1.3% for MCS-36, whereas both had similar 0.6% lower HR for hospitalization per point (all P < 0.0001)., Conclusions: The use of the SF-12 alone or as part of a larger survey is valid in dialysis patients. Composite scores from the SF-12 and SF-36 have similar prognostic association with death and hospitalization risk. Prospective longitudinal studies of SF-12 surveys that consider responsiveness to specific clinical, situational, and interventional changes are needed in this population.

Background and Objectives: The objective of this study was to evaluate epidemiology and outcomes of a large in-center nocturnal hemodialysis (INHD) program., Design, Setting, Participants, & Measurements: This case-control study compared patients who were on thrice-weekly INHD from 56 Fresenius Medical Care, North America facilities with conventional hemodialysis patients from 244 facilities within the surrounding geographic area. All INHD cases and conventional hemodialysis control subjects who were active as of January 1, 2007, were followed until December 31, 2007, for evaluation of mortality and hospitalization., Results: As of January 1, 2007, 655 patients had been on INHD for 51 +/- 73 d. Patients were younger, there were more male and black patients, and vintage was longer, but they had less diabetes compared with 15,334 control subjects. Unadjusted hazard ratio was 0.59 for mortality and 0.76 for hospitalization. After adjustment for case mix and access type, only hospitalization remained significant. Fewer INHD patients were hospitalized (48 versus 59%) with a normalized rate of 9.6 versus 13.5 hospital days per patient-year. INHD patients had greater interdialytic weight gains but lower BP. At baseline, hemoglobin values were similar, whereas albumin and phosphorus values favored INHD. Mean equilibrated Kt/V was higher in INHD patients related to longer treatment time, despite lower blood and dialysate flow rates., Conclusions: Patients who were on INHD exhibited excellent quality indicators, with better survival and lower hospitalization rates. The relative contributions of patient selection versus effect of therapy on outcomes remain to be elucidated in prospective clinical trials.

Background: Incremental achievement of quality indicator goals has been associated with progressive improvement in mortality and hospitalization risk in hemodialysis (HD) patients., Study Design: Descriptive cross-sectional study., Setting & Participants: All 33,879 HD patients treated at Fresenius Medical Care North America facilities for >90 days with scorable 36-Item Short Form Health Survey responses from January 1, 2006, to December 31, 2006., Predictor: We hypothesized that achieving up to 5 HD goals before the survey (albumin >or= 4.0 g/dL, hemoglobin of 11-12 g/dL, equilibrated Kt/V >or= 1.2, phosphorus of 3.5-5.5 mg/L, and absence of HD catheter) results in better self-reported quality of life (QoL)., Outcomes & Measurements: Distributions of Physical and Mental Component Summary (PCS/MCS) scores within and across quality indicator categories determined during the prior 90 days from survey date (compared using analysis of covariance and linear regression models, with adjustment for case-mix and each of the quality indicators)., Results: Incremental achievement of up to 5 goals was associated with progressively higher PCS and MCS scores (both P for trend < 0.001). Compared with patients meeting all 5 goals (n = 4,208; reference group), case-mix-adjusted PCS score was lower by 1.8 point with only 4 goals met (n = 11,785), 3.4 points for 3 goals (n = 10,906), 4.9 points for 2 goals (n = 5,119), 5.9 points for 1 goal (n = 1,592), and 7.8 points in the 269 patients who failed to meet any goal (each P < 0.001 vs the reference group). The corresponding decreases in case-mix-adjusted MCS scores were 1.0 point for 4 goals met, 1.7 point for 3 goals, 2.3 points for 2 goals, 3.0 points for 1 goal, and 4.7 points with no goal met, with each P < 0.001 compared with the MCS score from patients who achieved all 5 goals., Limitations: Potential residual confounding from unmeasured covariates., Conclusion: Patients progressively meeting more quality goals report incrementally better QoL. Further studies are needed to determine whether prospective achievement of quality goals will result in improved QoL for HD patients.

Mortality risk for dialysis patients is highest in the first year. We previously showed a 41% mortality benefit associated with a pilot case management program for incident hemodialysis patients (n = 918). The RightStart Program (RSP) provided prompt medical management and self-management education and was recently expanded to more facilities. We conducted a matched cohort analysis to validate the expanded program's continued effectiveness. Death risk was reduced for RS patients (n = 4308) versus matched controls (C; n = 4308) by 34% (hazard ratio = 0.66, P < 0.0001) at 120 d and 22% at 1 yr (hazard ratio = 0.78, P < 0.0001). RS patients had lower hospitalization during the first year (RS = 15.5 days per patient year versus C = 16.9, P < 0.01). At 120 d, more RS patients achieved hemoglobin 11 to 12 g/dl (RS = 22.4% versus C = 19.7%, P < 0.01), eKt/V > or = 1.2 (RS = 66% versus C = 53.5%, P < 0.01), albumin > or = 4.0 g/dl (RS = 26% versus C = 22%, P < 0.01), and phosphorus 3.5 to 5.5 mg/dl (RS = 52.4% versus C = 45.4%). At 120 d, RS patients had a greater reduction in catheter use (RS = 32% versus C = 25%, P < 0.01) and more vitamin D orders (RS = 60% versus C = 55%, P < 0.01). Expansion of RS to a larger incident patient population results in significant reduction of morbidity and mortality associated with improvement of intermediate outcomes.

Eighty-two percent (82%) of patients initiating hemodialysis in the United States in 2006 did so with a catheter as the functioning access. Even in patients who have been followed by nephrologists for 6 months or more, 74% of patients initiated dialysis with a catheter. This is a multifactoral problem that requires attention and solutions from all stakeholders, including the nephrologist, the vascular surgeon, the hospital, and the insurance industry, as well as the patient and family. We propose a series of specific proposals that include a process for the timely referral and timely placement of a permanent access based on the patient's estimated or measured glomerular filtration rate (GFR), and a 'pay-for-performance' measure for vascular surgeons and nephrologists who admit patients with functional permanent accesses; such pay for performance would place a higher value for patients who are admitted with a functional arteriovenous (AV) fistula than for patients who are admitted with an AV graft. We also propose that hospitals develop a less permissive process for placement of PICC (peripherally inserted central catheters) lines in patients with GFR <60 ml/min and to consider surgery for access placement as 'urgent'. Finally, a more proactive educational process for patients and their families, including an 'informed non-consent' for patients who defer placement of a permanent access needs to be considered. The morbidity, mortality, and health-care costs associated with prolonged catheter use mandate urgent attention to this problem.

Background: We hypothesized that a change from central venous catheters to a fistula or graft would improve short-term mortality risk in maintenance hemodialysis patients., Design: Prospective observational study., Setting & Participants: All maintenance in-center hemodialysis patients treated in Fresenius Medical Care, North America legacy facilities alive on January 1, 2007 with baseline laboratory data from December 2006., Predictor: Access type (fistula, catheter, or graft), determined on December 31, 2006, and monthly thereafter. Conversion from a catheter to a fistula or graft during the 4-month period from January 1 to April 30, 2007., Outcome: Mortality was tracked from May 1, 2007, to December 31, 2007. Standard and time-dependent Cox models were used to determine hazard risks (HRs) of death with and without adjustment for case-mix and laboratory values., Results: At baseline, 79,545 patients had 43% fistulas, 29% catheters, and 27% grafts. Mean age was 62 +/- 15 years, 54% were men, 51% were white, and 53% had diabetes. Compared with fistulas, unadjusted HRs of death were higher for grafts (1.22) and catheters (1.76; P < 0.001). In adjusted models, overall risk for grafts was decreased to 1.05 (95% limits, 1.003-1.100; P < 0.05) and approached that for fistulas consistently across multiple strata. Compared with patients who continued using a catheter, those who converted to either a graft or fistula had an HR of 0.69, whereas those who converted from a graft or fistula to a catheter had increased HRs to 2.12 (both P < 0.001). Similar trends were observed in the subset of incident patients (vintage < 90 days at study onset)., Limitations: Observational design with residual confounding from unmeasured patient, facility, and treatment-related factors., Conclusions: Catheters have the worst associated mortality risk. Changing from a catheter to a fistula or graft is associated with significantly improved survival. The risk for grafts approached that of fistulas, providing an alternative to prolonged catheter exposure and potentially less hazardous "bridge" toward a fistula.

Use of warfarin, clopidogrel, or aspirin associates with mortality among patients with ESRD, but the risk-benefit ratio may depend on underlying comorbidities. Here, we investigated the association between these medications and new stroke, mortality, and hospitalization in a retrospective cohort analysis of 1671 incident hemodialysis patients with preexisting atrial fibrillation. We followed patient outcomes from the time of initiation of dialysis for an average of 1.6 yr. Compared with nonuse, warfarin use associated with a significantly increased risk for new stroke (hazard ratio 1.93; 95% confidence interval 1.29 to 2.90); clopidogrel or aspirin use did not associate with increased risk for new stroke. Analysis using international normalized ratio (INR) suggested a dose-response relationship between the degree of anticoagulation and new stroke in patients on warfarin (P = 0.02 for trend). Warfarin users who received no INR monitoring in the first 90 d of dialysis had the highest risk for stroke compared with nonusers (hazard ratio 2.79; 95% confidence interval 1.65 to 4.70). Warfarin use did not associate with statistically significant increases in all-cause mortality or hospitalization. In conclusion, warfarin use among patients with both ESRD and atrial fibrillation associates with an increased risk for stroke. The risk is greatest in warfarin users who do not receive in-facility INR monitoring.

Objective: We examined the protein anabolic effects of Pro-Stat 64, a high nitrogen-containing, enzyme-hydrolyzed, tryptophan-fortified, collagen protein supplement administrated during hemodialysis, at two different dosing regimens., Design: This was a randomized, controlled, prospective study with 3 different groups: control, single dose of supplementation, and double dose of supplementation., Setting: This study was performed at a clinical research center., Patients: Six prevalent chronic hemodialysis (HD) patients were enrolled: 5 males, 1 female, 4 African Americans, and 2 Caucasians. Their mean age was 45 +/- 11 years (S.D.). Two patients were diabetic., Methods: Protein turnover studies were performed using amino-acid (AA) balance and primed constant infusion of L-(1-(13)C) leucine., Main Outcome Measure: Whole-body protein balance was determined according to substrate kinetics., Results: There were no statistically significant difference at any time point between protocols for blood chemistries and hormonal markers, except for minor variations in plasma glucose. All plasma AA groups displayed decreases during a control study, in which no supplementation was given. Compared with the control group, plasma nonessential AA and total AA concentrations were statistically significantly higher during HD after both single and double doses of supplementation. The forearm arteriovenous AA balance was statistically significantly better for essential, nonessential, and total AA uptake after both single-dose and double-dose supplementation compared with the control group, except for nonessential AA, which was significantly better only after a double dose. Whole-body protein breakdown and net protein balance were statistically significantly better during HD with a double-dose administration in a dose-dependent manner, compared with the control and single-dose groups., Conclusions: Oral AA supplementation alone improves whole-body and skeletal muscle protein anabolism in a dose-dependent manner in chronic HD patients. These data should be taken into account during clinical decision-making or when designing clinical trials of nutritional supplementation.

Background: We evaluated whether incremental achievement of up to 8 facility quality goals was associated with improvement in facility-specific mortality and hospitalization rates., Study Design: Prospective observational study., Setting & Participants: 1,085 Fresenius Medical Care, North America facilities providing hemodialysis (HD) for 25 or more patients during January 2006., Measurements: The facility average for the period up to December 31, 2006, was used to determine achievement of each goal for equilibrated Kt/V, missed HD treatments, hemoglobin level, bicarbonate level, albumin level, phosphorus level, fistulae, and HD catheters. Linear regression models were used to relate facility-wide achievement of goals with facility-specific hospital days and standardized mortality ratios., Results: Most facilities (64%) achieved 2 to 4 of 8 goals, with only 8% meeting more than 5 quality goals. Achieving more than 5 goals averaged 3.5 fewer hospital days/patient-year and 20% lower standardized mortality ratios (all P < 0.001). The incremental number of goals met also was associated with improvement in facility mortality (P < 0.001) and hospital days (P < 0.001). Catheter and albumin level goals were achieved least (6% and 9% of facilities, respectively), but they had the best outcomes. Facilities achieving more than 5 goals had older patients (64.0 versus 61.5 years; P < 0.001), fewer African American patients (16% versus 38%; P < 0.001), and fewer women (44% versus 46%; P = 0.003) compared with the average., Limitations: Observational design with residual confounding from unmeasured patient-, facility-, and treatment-related factors., Conclusions: Achieving more facility quality goals was significantly associated with better facility-based measurements of patient outcomes. Although these results do not establish a causal relationship, findings agree with the present practice of monitoring facility performance for continuous quality improvement.

The International Quotidian Dialysis Registry (IQDR) is a global initiative designed to study practices and outcomes associated with the use of hemodialysis regimens of increased frequency and/or duration. Several small studies suggest that compared with conventional hemodialysis (HD), short-daily, nocturnal, and long conventional HD regimens may improve surrogate endpoints and quality of life. However, methodologically robust comparisons on hard outcomes are sorely lacking. The IQDR represents the first-ever attempt to aggregate long-term follow-up data from centers utilizing alternative HD regimens worldwide, and will have adequate statistical power to examine the effects of these regimens on multiple clinical endpoints, including mortality. To date, the IQDR has enrolled patients from Canada, the United States, Australia, and New Zealand, with plans in place to begin linking with additional commercial databases and national registries. This fifth annual report of the IQDR describes (1) a proposed governance structure that will facilitate international collaboration, stakeholder input and funding; (2) data sources and participating registries; (3) recruitment to date and patient baseline characteristics; and (4) an agenda for future research.

Background and Objectives: Patient knowledge about chronic hemodialysis (CHD) is important for effective self-management behaviors, but little is known about its association with vascular access use., Design, Setting, Participants, & Measurements: Prospective cohort of adult incident CHD patients from May 2002 until November 2005 and followed for 6 mo after initiation of hemodialysis (HD). Patient knowledge was measured using the Chronic Hemodialysis Knowledge Survey (CHeKS). The primary outcome was dialysis access type at: baseline, 3 mo, and 6 mo after HD initiation. Secondary outcomes included anemia, nutritional, and mineral laboratory measures., Results: In 490 patients, the median (interquartile range) CHeKS score (0 to 100%) was 65%[52% to 78%]. Lower scores were associated with older age, fewer years of education, and nonwhite race. Patients with CHeKS scores 20 percentage points higher were more likely to use an arteriovenous fistula or graft compared with a catheter at HD initiation and 6 mo after adjustment for age, sex, race, education, and diabetes mellitus. No statistically significant associations were found between knowledge and laboratory outcome measures, except for a moderate association with serum albumin. Potential limitations include residual confounding and an underpowered study to determine associations with some clinical measures., Conclusions: Patients with less dialysis knowledge may be less likely to use an arteriovenous access for dialysis at initiation and after starting hemodialysis. Additional studies are needed to explore the impact of patient dialysis knowledge, and its improvement after educational interventions, on vascular access in hemodialysis.

Many prescribe anticoagulants and antiplatelet medications to prevent thromboembolic events and access thrombosis in dialysis patients despite limited evidence of their efficacy in this population. This retrospective cohort study examined whether use of warfarin, clopidogrel, and/or aspirin affected survival in 41,425 incident hemodialysis patients during 5 yr of follow-up. The prescription frequencies for warfarin, clopidogrel, and aspirin were 8.3, 10.0, and 30.4%, respectively, during the first 90 d of initiating chronic hemodialysis. Compared with the 24,740 patients receiving none of these medications, Cox proportional hazards analysis suggested that exposure to these medications was associated with increased risk for mortality (warfarin hazard ratio [HR] 1.27 [95% confidence interval (CI) 1.18 to 1.37]; clopidogrel HR 1.24 [95% CI 1.13 to 1.35]; and aspirin HR 1.06 [95% CI 1.01 to 1.11]). The increased mortality associated with warfarin or clopidogrel use remained in stratified analyses. A covariate- and propensity-adjusted time-varying analysis, which accounted for longitudinal changes in prescription, produced similar results. In addition, matching for treatment facility and attending physician revealed similar associations between prescription and mortality. We conclude that warfarin, aspirin, or clopidogrel prescription is associated with higher mortality among hemodialysis patients. Given the possibility of confounding by indication, randomized trials are needed to determine definitively the risk and benefit of these medications.

Background: Inflammation in an ESRD patient may impact responsiveness to erythropoiesis-stimulating agent (ESA) therapy. We sought to investigate the association between C-reactive protein (CRP) levels and average per-administration epoetin alfa (EPO) dose over 3 months following a CRP measurement., Methods: The study is a retrospective cohort study of hemodialysis patients >or=18 years of age receiving care at a Fresenius Medical Care-North America facility between 1 July 2000 and 30 June 2002 who had no history of peritoneal dialysis. All patients had >or=1 CRP measurement and >or=3 months of recorded information before the CRP measurement (entry period). We evaluated the association between CRP levels and average hemoglobin (Hb) and per-administration EPO dose over the 3 months following the CRP measurement., Results: We identified 1754 patients with a CRP measurement; mean age was 62.6 years (SD 14.1), 51.5% were male, 56.2% were white and the median CRP value was 2.04 mg/dL (20.4 mg/L). Patients in the upper CRP quartiles were more likely to be older, recently hospitalized; have a catheter vascular access; have lower albumin, Hb and transferrin saturation levels and greater EPO doses. In the subsequent 3 months, EPO doses but not Hb levels were significantly higher for patients in the highest CRP quartile [3.21 mg/dL (32.1 mg/L)] (P = 0.01)., Conclusions: Inflammation as measured by an elevated CRP level appears to be an independent predictor of greater ESA dose requirements. Patients with the highest CRP levels required significantly higher ESA doses to achieve comparable Hb levels even after controlling for potential confounding variables.

Background: To determine the most significant potentially actionable clinical variables associated with mortality and hospitalization risk in hemodialysis (HD) patients., Study Design: Cohort study., Setting & Participants: Adult maintenance HD patients in the Fresenius Medical Care, North America database as of January 1, 2004, with baseline information from October 1, 2003, to December 31, 2003, comprising approximately 26% of the US HD population., Predictors: Case-mix (age, sex, race, diabetes, vintage, and body surface area), vascular access, and laboratory (albumin, equilibrated Kt/V, hemoglobin, calcium, phosphorus, creatinine, bicarbonate, biointact parathyroid hormone, transferrin saturation, and white blood cell count) variables., Outcomes: 1-year mortality and hospitalization risk from January 1 to December 31, 2004., Measurements: Cox proportional hazards models for death and hospitalization., Results: The cohort (N = 78,420) had a mean age of 61.4 +/- 15.0 years, 47% were women, 49% were white, 41% were black race (10% defined as "other"), and 52% had diabetes. The top 5 actionable variables were the same for mortality and hospitalization. Final case-mix plus laboratory-adjusted hazard ratios for these top 5 actionable variables indicate 177% increased risk of death and 67% increased risk of hospitalization per 1-g/dL decrease in albumin level, 39% and 45% greater risk with catheters compared with fistulas, 18% and 9% greater risk per 1-mg/dL greater phosphorus level, 11% and 9% lower risk per 1-g/dL greater hemoglobin level, and 5% and 2% greater risk per 0.1-unit decrease in equilibrated Kt/V, respectively (all P < 0.0001)., Limitations: Observational cross-sectional study with limited comorbidity adjustment (for diabetes)., Conclusion: The same variables are associated with both mortality and hospitalization in HD patients. The top 5 potentially actionable variables are readily identifiable, with albumin level and catheter use the most prominent, and all 5 are appropriate targets for improvement.

Background: Medicare data indicate that black hemodialysis patients receive greater doses of erythropoietin (EPO) than white patients when achieving similar hemoglobin levels. We confirmed and evaluated this observed association between race and EPO dose., Study Design: Cross-sectional cohort study., Setting & Participants: Primary Medicare-insured white (57%) and black (43%) adult long-term hemodialysis patients treated by Fresenius Medical Care who received EPO from January 1 to 31, 2004 (N = 44,721)., Predictor: White/black race., Outcomes: Average weekly EPO dose., Measurements: Associations between race and baseline demographic and laboratory variables were evaluated by using logistic and linear regression models. Correlates of log-transformed weekly EPO dose were determined using linear regression models., Results: Black patients received 12.6% more EPO than white patients (95% limits, 10.9% to 14.3%; P < 0.001). This racial difference in EPO dose was observed across similar hemoglobin levels despite fewer catheters (P < 0.001) and fewer prior hospitalization events in black patients (P = 0.002). Black patients were younger and had larger body size and greater albumin and biointact parathyroid hormone levels, but lower equilibrated Kt/V and white blood cell counts (all P < 0.001). In the 95th percentile of EPO dose (those receiving > 60,000 U/wk), there was a greater proportion of black patients (6% of total black population compared with only 4% in all white patients; P < 0.001). The difference in EPO dose between black and white patients was modified by age and was significant at ages younger than 45 and 65 years or older., Limitations: Observational study limited to white and black adult Medicare patients only, correlating with EPO doses from a single month, without adjustment for comorbid conditions., Conclusions: Black patients were administered approximately 12% greater EPO doses than white patients while achieving similar hemoglobin levels. We identified variables that differed across race that may explain this difference, but they were either not actionable or presented limited opportunity for intervention. Additional studies are needed to define a physiological (or pathological) basis for these observations.

Alternative hemodialysis (HD) schedules, including short-daily and nocturnal HD, continue to proliferate, with the hope of offering improved patient outcomes. Three nights per week and every other night, nocturnal HD are now being provided to more patients worldwide, both at home and in-center. However, alternative HD schedules are still experimental in most centers, and studies establishing the efficacy of these therapies with respect to major clinical outcomes are needed. Endorsed by the National Institutes of Health, the International Quotidian Dialysis Registry is an international collaboration that was established in 2002 to prospectively study large numbers of patients treated with alternate HD schedules. The Registry will ultimately allow alternate HD modalities to be compared to conventional thrice-weekly HD with respect to clinical endpoints, including mortality, using a prospective cohort study. To date, the Registry has enrolled 182, 1193, and 740 subjects from Canada, the United States, and Australia, respectively. This report is the fourth annual update and describes recruitment progress, baseline characteristics of enrolled patients, and worldwide prescription patterns.

Biomarkers of inflammation, especially C-reactive protein (CRP), have been consistently shown to predict poor outcomes in chronic hemodialysis (CHD) patients. However, the determinants of CRP and the value of its monitoring in CHD patients have not been well defined. We conducted a retrospective cohort study to evaluate possible determinants of the inflammatory response in CHD patients with a focus on dialysis catheter utilization. Monthly CRP were measured in 128 prevalent CHD patients (mean age 56.6 years [range 19-90], 68% African Americans, 39% diabetics [DM]) over a mean follow-up of 12 months (range 2-26 months). There were a total of 2405 CRP measurements (median 5.7 mg/L; interquartile range [IQR] 2.4-16.6 mg/L). The presence of a dialysis catheter (p<0.002), cardiovascular disease (p=0.01), male gender (p=0.005), higher white blood cell count (p<0.0001), elevated phosphorus (p=0.03), and lower cholesterol (p=0.02) and albumin (p<0.0001) concentrations were independent predictors of elevated CRP in the multivariate analysis. Additionally, CRP levels were significantly associated with the presence of a catheter, when comparing the levels before and after catheter insertion (p=0.002) as well as before and after catheter removal (p=0.009). Our results indicate that the presence of a hemodialysis catheter is an independent determinant of an exaggerated inflammatory response in CHD patients representing a potentially modifiable risk factor.

The role of the dialysis unit Medical Director has evolved over time to an expanded set of roles from one that used to be strictly "medical" to one that is more "managerial." Physicians providing these Medical Director services are facing increasing demands for a leadership role regarding clinical quality improvement and measurement of performance in core areas of care within the dialysis program. The dialysis Medical Director is asked to lead in group decision-making, in analyzing core process and patient outcomes and in stimulating a team approach to Continuous Quality Improvement (CQI) and patient safety. For the end-stage renal disease program, national quality expectations in dialysis care have stimulated the dialysis providers to measure, report and respond consistently in an effort to provide a higher level of cost-efficient care. Medical Directors are usually contractually linked to the dialysis programs for which they provide oversight and their contracts are explicit about the relationship they maintain and the role they are expected to play within dialysis companies (often called "provider organizations"). The evolution of the Medical Director role has led to a close relationship between the company that provides the dialysis services and the physician providing the medical oversight.

Background and Objectives: Annualized mortality rates of chronic hemodialysis (CHD) patients in their first 90 d of treatment range from 24 to 50%. Limited studies also show high hospitalization rates. It was hypothesized that a structured quality improvement program (RightStart), focused on medical needs and patient education and support, would improve outcomes for incident CHD patients., Design, Setting, Participants, & Measurements: A total of 918 CHD incident patients were prospectively enrolled in a multicenter RightStart Program, and compared with a time-concurrent group of 1020 control patients from non-RightStart clinics. RightStart patients received 3 mo of intervention in management of anemia, dosage of dialysis, nutrition, and dialysis access and a comprehensive educational program. Outcomes were tracked for up to 12 mo., Results: At 3 mo, RightStart patients had higher albumin and hematocrit values. Dose of dialysis and permanent access placement were not statistically significantly different from control subjects. Compared with baseline, Mental Composite Score for RightStart patients improved significantly. Mean hospitalization days per patient year were reduced with RightStart versus control subjects. Mortality rates at 3, 6, and 12 mo were 20, 18, and 17 for RightStart patients versus 39, 33, and 30 deaths per 100 patient-years for control subjects, respectively., Conclusions: A structured program of prompt medical and educational strategies in incident CHD patients results in improved morbidity and mortality that last up to 1 yr.

Objective: Our objective was to estimate the effect of an improvement in nutrition, represented by albumin concentrations, on hospitalization, mortality, and Medicare end-stage renal disease (ESRD) program cost., Design: Based on published trials, the impact of an improvement in serum albumin of +0.2 g/dL from a hypothetical nutritional program for severely malnourished patients with albumin < or = 3.5 g/dL (base case) was estimated by reassigning patients to higher albumin categories, along with outcome risks associated with the new albumin category., Setting: Data from Fresenius Medical Care North America (Waltham, MA) were utilized in regression models to determine the association between albumin and change in albumin concentration with outcomes., Results: Albumin < or = 3.5 g/dL was associated with a > 2-fold increase in death and hospitalization risk, compared to > or = 4 g/dL (P < .001) in this population. An increase in albumin concentration was associated with a lower risk of death and hospitalization, whereas a declining albumin concentration led to worse outcomes. Projections for the United States dialysis population from the base case showed approximately 1400 lives saved, approximately 6000 hospitalizations averted, and approximately $36 million in Medicare cost savings resulting from a reduction of approximately 20,000 hospital days. A sensitivity analysis, varying the albumin response to +0.1 and +0.3 g/dL combined with varying albumin responder rates to 25% and 75% of patients, revealed robust results., Conclusion: Nutritional interventions that increase serum albumin by > or = 0.2 g/dL (e.g., via oral nutritional supplements) may lead to considerable improvements in mortality, hospitalization, and treatment costs.