George Ting

In-center hemodialysis six times per week versus three times per week

BACKGROUND In this randomized clinical trial, we aimed to determine whether increasing the frequency of in-center hemodialysis would result in beneficial changes in left ventricular mass, self-reported physical health, and other intermediate outcomes among patients undergoing maintenance hemodialysis. METHODS Patients were randomly assigned to undergo hemodialysis six times per week (frequent hemodialysis, 125 patients) or three times per week (conventional hemodialysis, 120 patients) for 12 months. The two coprimary composite outcomes were death or change (from baseline to 12 months) in left ventricular mass, as assessed by cardiac magnetic resonance imaging, and death or change in the physical-health composite score of the RAND 36-item health survey. Secondary outcomes included cognitive performance; self-reported depression; laboratory markers of nutrition, mineral metabolism, and anemia; blood pressure; and rates of hospitalization and of interventions related to vascular access. RESULTS Patients in the frequent-hemodialysis group averaged 5.2 sessions per week; the weekly standard Kt/V(urea) (the product of the urea clearance and the duration of the dialysis session normalized to the volume of distribution of urea) was significantly higher in the frequent-hemodialysis group than in the conventional-hemodialysis group (3.54±0.56 vs. 2.49±0.27). Frequent hemodialysis was associated with significant benefits with respect to both coprimary composite outcomes (hazard ratio for death or increase in left ventricular mass, 0.61; 95% confidence interval [CI], 0.46 to 0.82; hazard ratio for death or a decrease in the physical-health composite score, 0.70; 95% CI, 0.53 to 0.92). Patients randomly assigned to frequent hemodialysis were more likely to undergo interventions related to vascular access than were patients assigned to conventional hemodialysis (hazard ratio, 1.71; 95% CI, 1.08 to 2.73). Frequent hemodialysis was associated with improved control of hypertension and hyperphosphatemia. There were no significant effects of frequent hemodialysis on cognitive performance, self-reported depression, serum albumin concentration, or use of erythropoiesis-stimulating agents. CONCLUSIONS Frequent hemodialysis, as compared with conventional hemodialysis, was associated with favorable results with respect to the composite outcomes of death or change in left ventricular mass and death or change in a physical-health composite score but prompted more frequent interventions related to vascular access. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov number, NCT00264758.).

Short daily haemodialysis: survival in 415 patients treated for 1006 patient-years.

BACKGROUND Survival statistics for daily haemodialysis are lacking as most centres providing this have treated only a small number of patients for short observation times. We pooled our 23-year, 1006-patient-year, five-centre experience of 415 patients treated by short daily haemodialysis. METHODS One hundred and fifty patients were treated in-centre, most because of medical complications and 265 by home or self-care haemodialysis. Patients were on daily haemodialysis for 29 +/- 31 (0-272) months. Forty-two percent had primary and 31% had secondary renal failure. Treatment time was 136 +/- 35 min, frequency 5.8 +/- 0.5 times/week and weekly stdKt/V 2.7 +/- 0.55. RESULTS Eighty-five patients (20%) died; 5-year cumulative survival was 68 +/- 4.1% and 10-year survival was 42 +/- 9%. Age, secondary renal failure and in-centre dialysis were associated with mortality, while gender, frequency of dialysis (5, 6 or 7 per week), continent, country and blood access were not. Survival was compared with matched patients from the USRDS 2005 Data Report using the standardized mortality ratio and cumulative survival curves. Both comparisons showed that the survival of the daily haemodialysis patients was 2-3 times higher and the predicted 50% survival time 2.3-10.9 years longer than that of the matched US haemodialysis patients. Survival of patients dialyzing daily at home was similar to that of age-matched recipients of deceased donor renal transplants. CONCLUSIONS Survival of patients on short daily haemodialysis was 2-3 times better than that of matched three times weekly haemodialysis patients reported by the USRDS.

The case for dialy dialysis: Its impact on costs and quality of life

Abstract Research suggests daily hemodialysis may improve clinical outcomes. To date, a comprehensive review of its implications on quality of life has not been performed, and little is known about its economic impact. We conducted an economic evaluation comparing short daily or nocturnal hemodialysis with thrice-weekly conventional in-center dialysis. Data on the quality of life and clinical effects of daily dialysis were obtained from more than 60 reports from 13 daily dialysis programs around the world (n = 197). Cost data were derived principally from the US Renal Data System, Centers for Disease Control, and Medicare Payment Advisory Commission. Resource use during daily hemodialysis was modeled after two ongoing programs in the United States. Results suggest that patients feel better and direct treatment costs could be reduced with daily dialysis. Costs are sensitive to assumptions about the effect of daily dialysis on hospital days. Reductions of at least 8% in hospital days are required for these modalities to be cost saving compared with documented reductions of 30% to 100%. Larger well-controlled studies of daily versus conventional dialysis would be helpful to determine whether daily dialysis fulfills these promises. Medicare policy, which limits payment for most patients to three dialysis treatments weekly, poses a disincentive to more widespread adoption among dialysis centers. Given this constraint to broader acceptance, we address several policy options to gain a better understanding of the potential risks and benefits of daily dialysis.

Risk of Vascular Access Complications with Frequent Hemodialysis

Frequent hemodialysis requires using the vascular access more often than with conventional hemodialysis, but whether this increases the risk for access-related complications is unknown. In two separate trials, we randomly assigned 245 patients to receive in-center daily hemodialysis (6 days per week) or conventional hemodialysis (3 days per week) and 87 patients to receive home nocturnal hemodialysis (6 nights per week) or conventional hemodialysis, for 12 months. The primary vascular access outcome was time to first access event (repair, loss, or access-related hospitalization). Secondary outcomes were time to all repairs and time to all losses. In the Daily Trial, 77 (31%) of 245 patients had a primary outcome event: 33 repairs and 15 losses in the daily group and 17 repairs, 11 losses, and 1 hospitalization in the conventional group. Overall, the risk for a first access event was 76% higher with daily hemodialysis than with conventional hemodialysis (hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.11-2.79; P=0.017); among the 198 patients with an arteriovenous (AV) access at randomization, the risk was 90% higher with daily hemodialysis (HR, 1.90; 95% CI, 1.11-3.25; P=0.02). Daily hemodialysis patients had significantly more total AV access repairs than conventional hemodialysis patients (P=0.011), with 55% of all repairs involving thrombectomy or surgical revision. Losses of AV access did not differ between groups (P=0.58). We observed similar trends in the Nocturnal Trial, although the results were not statistically significant. In conclusion, frequent hemodialysis increases the risk of vascular access complications. The nature of the AV access repairs suggests that this risk likely results from increased hemodialysis frequency rather than heightened surveillance.

Comparison of survival between short-daily hemodialysis and conventional hemodialysis using the standardized mortality ratio.

More frequent hemodialysis (5 or more times weekly, both short during the day and long overnight) has been shown to improve patient well‐being, reduce symptoms during and between treatments, and have beneficial effects on clinical outcomes. Because of the relatively small patient sample sizes, there are little or no data on mortality from any single study at this time. This study compares survival in 117 U.S. patients treated by short‐daily hemodialysis in 2003 and 2004, with patients reported in the 2003 data from the United States Renal Data System (USRDS). Expected mortality was calculated from the USRDS and compared with observed actual mortality. The standardized mortality ratio (SMR) was used to adjust for differences in patient age, sex, race, and cause of renal failure. The SMR for the short‐daily hemodialysis patients was 0.39, statistically significantly better (p<0.005) than data from the overall U.S. population of hemodialysis patients and indicating that daily hemodialysis patients had a 61% better survival. Patients treated by short‐daily hemodialysis have a better survival rate than comparable populations treated by conventional hemodialysis.

Daily Hemodialysis: Dialysis for the Next Century

There are currently over 150 patients receiving daily hemodialysis in over 12 centers worldwide. The experiences of over 200 daily hemodialysis patients spanning 30 years have been reviewed. The reports uniformly describe subjective and objective improvements. There are decreased symptoms during and after dialysis, improved functional status, and better quality-of-life ratings. There are improved nutritional indices, improved blood pressure with fewer blood pressure medications, and improved hematocrit with reduced transfusion or eythropoietin requirements. There also appear to be economic advantages, related to the significant reductions in the need for recombinant human erythropoietin and blood pressure medications. Early data suggest that there may be a significant decrease in days of hospitalization for very ill patients as well. This is important clinically and financially when the global costs of caring for dialysis patients are considered. Substantial issues remain before daily hemodialysis will be widely accepted. These include logistical problems (additional time for transportation, set up and disinfection), economic problems (increased supply costs or labor associated with more frequent treatments), and medical problems (deficiency syndromes and blood access). Technological improvements are close to overcoming many of the recognized problems, although additional payor education, research into deficiency syndromes, and an even greater focus on creating natural arterio-venous fistulae all need to occur before daily hemodialysis is more widely accepted. We are convinced, however, that daily dialysis will be increasingly used in the next century because it is more physiologic, makes many patients feel much better, produces better outcomes, and decreases overall cost for end-stage renal disease patients compared with current dialysis regimes.

Survival with short-daily hemodialysis: Association of time, site, and dose of dialysis

In thrice‐weekly hemodialysis, survival correlates with the length of time (t) of each dialysis and the dose (Kt/V), and deaths occur most frequently on Mondays and Tuesdays. We studied the influence of t and Kt/V on survival in 262 patients on short‐daily hemodialysis (SDHD) and also noted death rate by weekday. Contingency tables, Kaplan‐Meier analysis, regression analysis, and stepwise Cox proportional hazard analysis were used to study the associations of clinical variables with survival. Patients had been on SDHD for a mean of 2.1 (range 0.1–11) years. Mean dialysis time was 12.9 ± 2.3 h/wk and mean weekly stdKt/V was 2.7 ± 0.5. Fifty‐two of the patients died (20%) and 8‐year survival was 54 ± 5%. In an analysis of 4 groups by weekly dialysis time, 5‐year survival continuously increased from 45 ± 8% in those dialyzing <12 hours to 100% in those dialyzing >15 hours without any apparent threshold. There was no association between Kt/V and survival. In Cox proportional hazard analysis, 4 factors were independently associated with survival: age in years Hazard Ratio (HR)=1.05, weekly dialysis hours HR=0.84, home dialysis HR=0.50, and secondary renal disease HR=2.30. Unlike conventional HD, no pattern of excessive death occurred early in the week during SDHD. With SDHD, longer time and dialysis at home were independently associated with improved survival, while Kt/V was not. Homedialysis and dialysis 15+ h/wk appear to maximize survival in SDHD.

Daily dialyses decrease plasma levels of brain natriuretic peptide (BNP), a biomarker of left ventricular dysfunction

Brain natriuretic peptide or B‐type natriuretic peptide (BNP) is a sensitive marker of heart disease. Plasma levels of BNP increase in left ventricular failure and determination of plasma BNP has become a useful tool in the diagnosis of heart failure. Hemodialysis (HD) patients may have elevated plasma levels of BNP, particularly predialysis, that correlate with echocardiographic signs of left ventricular dysfunction. High BNP levels are also a strong predictor of mortality in both nonrenal and HD patients. We studied plasma BNP levels in patients who changed from conventional thrice‐weekly dialysis to daily dialysis 6 times a week while maintaining a total weekly time on dialysis of 12 hr. Twelve HD patients, mean age 55 years, had 4 hr of conventional thrice‐weekly treatment for 4 weeks. Predialysis and postdialysis blood samples were obtained at the last dialysis. Patients were then dialyzed for 2 hr, 6 times weekly, for 4 weeks (daily dialysis). Again, predialysis and postdialysis blood samples were collected at the last HD. Brain natriuretic peptide plasma concentrations were determined by immunoradiometric assay. Predialysis BNP levels decreased from 194±51 ng/L (68±19 pmol/L; mean+SE) during thrice‐weekly HD to 113±45 ng/L (41±18 pmol/L; p=0.001) after 4 weeks on daily dialysis. With thrice‐weekly HD, predialysis BNP levels were higher than postdialysis levels: 120±26 ng/L (39±8 pmol/L; p=0.059). With daily dialysis, predialysis BNP levels did not differ significantly from postdialysis levels. Elevated predialysis plasma levels of BNP, considered sensitive and early markers of left ventricular dysfunction, decreased when patients were changed from conventional thrice‐weekly HD to daily dialysis maintaining total hours of dialysis per week constant. Given the accumulated evidence that BNP is a biomarker of left ventricular dysfunction and can be used for risk stratification and guidance in pharmacotherapy of heart failure, daily dialysis appears to lead to less cardiac distress.

Challenges to enrollment and randomization of the Frequent Hemodialysis Network (FHN) Daily Trial.

BACKGROUND The US National Institutes of Health (NIH) and Centers for Medicare and Medicaid Services (CMS) sponsored a randomized clinical trial comparing six versus three times per week in-center hemodialysis (the Frequent Hemodialysis Network [FHN] Daily Trial), to test the effects of frequent hemodialysis on an array of intermediate outcomes. Herein we report challenges to enrollment and randomization into the trial. METHODS Screening and enrollment was tracked at all participating dialysis clinics and specific reasons for dropout after baseline assessment were recorded for all enrolled subjects. Reasons for consent refusal were recorded in a subset of (10 out of 65) sites. RESULTS The trial screened 6276 hemodialysis patients on three times weekly hemodialysis in 65 hemodialysis clinics, 3481 (55%) were considered eligible for enrollment, and 3124 (90%) were approached for consent; 378 (12%) consented and 245 were randomized (65% of those enrolled). Prospective subjects chose not to participate primarily because of the anticipated time required for three extra treatments per week and the difficulties in following the protocol. CONCLUSIONS Recruitment into the FHN Daily Trial proved challenging but the goal of 250 randomized subjects was almost met.

Design and Rationale of Health-Related Quality of Life and Patient-Reported Outcomes Assessment in the Frequent Hemodialysis Network Trials

Background: End-stage renal disease patients experience significant impairments in health-related quality of life (HRQOL). Testing various strategies to improve patient HRQOL in multicenter clinical trials, such as the Frequent Hemodialysis Network (FHN) trials is vitally important. Aims: Theaim of this paper is to describe the design and conduct of HRQOL and patient-reported outcomes (PRO) assessment in the FHN trials. Methods: In the FHN trials, HRQOL was examined as a multidimensional concept, and the SF-36 RAND Physical Health Composite score was one of the co-primary outcomes. The instruments completed to assess HRQOL included the Medical Outcomes Study Short Form SF-36, Health Utilities Index 3, Sleep Problems Index, Beck Depression Inventory and feeling thermometer. These instruments have been shown to have high reliability, validity and responsiveness to change in the end-stage renal disease population. Additional items evaluating PRO including sexual function, time to recovery after dialysis and patients’ self-perceived burden to caregiver were also assessed. All questionnaires were administered by trained interviewers using computer-assisted telephone interviewing to ensure blinding and minimizing selection bias. Interim analysis reveals that these instruments can be used to collect a comprehensive set of HRQOL measures with minimal patient burden. Conclusions: Accurate measurement of HRQOL and PRO can help us test whether hemodialysis interventions improve the health and well-being of this compromised patient population. We have shown that a comprehensive set of HRQOL measures can be centrally collected through telephone interviews in a blinded fashion, in a way that is well tolerated with minimum respondent burden.