Effect of daily hemodialysis on depressive symptoms and postdialysis recovery time: interim report from the FREEDOM (Following Rehabilitation, Economics and Everyday-Dialysis Outcome Measurements) Study.

BACKGROUND: Clinical depression and postdialysis fatigue are important concerns for patients with kidney failure and can have a negative impact on quality of life and survival. STUDY DESIGN: The FREEDOM (Following Rehabilitation, Economics and Everyday-Dialysis Outcome Measurements) Study is an ongoing prospective cohort study investigating the clinical and economic benefits of daily (6 times per week) hemodialysis (HD). In this interim report, as part of an a priori planned analysis, we examine the long-term impact of daily HD on depressive symptoms, measured using the Beck Depression Inventory (BDI) survey, and postdialysis recovery time, measured using a previously validated questionnaire. SETTING & PARTICIPANTS: Adult patients initiating daily HD with a planned 12-month follow-up. OUTCOMES & MEASUREMENTS: The BDI survey and postdialysis recovery time question were administered at baseline, and changes were assessed at months 4 and 12. RESULTS: 239 participants were enrolled (intention-to-treat cohort) and 128 completed the study (per-protocol cohort). Mean age was 52 years, 64% were men, 55% had an arteriovenous fistula, and 90% transitioned from in-center HD therapy. In the per-protocol cohort, there was a significant decrease in mean BDI score over 12 months (11.2 [95% CI, 9.6-12.9] vs 7.8 [95% CI, 6.5-9.1]; P<0.001). For robustness, the intention-to-treat analysis was performed, yielding similar results. The percentage of patients with depressive symptoms (BDI score>10) significantly decreased during 12 months (41% vs 27%; P=0.03). Similarly, in the per-protocol cohort, there was a significant decrease in postdialysis recovery time over 12 months (476 [95% CI, 359-594] vs 63 minutes [95% CI, 32-95]; P<0.001). The intention-to-treat analysis yielded similar results. The percentage of patients experiencing prolonged postdialysis recovery time (>or=60 minutes) also significantly decreased (81% vs 35%; P=0.001). LIMITATIONS: Observational study with lack of control arm. CONCLUSIONS: Daily HD is associated with long-term improvement in depressive symptoms and postdialysis recovery time.

Scope and design of the Following Rehabilitation, Economics and Everyday-Dialysis Outcome Measurements (FREEDOM) Study.

BACKGROUND: Conventional thrice-weekly hemodialysis (HD) has limited the ability to generate further improvements in patient quality of life, morbidity, and mortality. Daily HD (DHD) offers the promise of providing clinical and economic benefits. The objectives of the Following Rehabilitation, Economics and Everyday-Dialysis Outcome Measurements Study are to evaluate outcomes of DHD (6 times/wk) with the NxStage System One (NxStage Medical Inc, Lawrence, MA) device. DESIGN: Cohort study with matched control group. SETTING & PARTICIPANTS: The DHD group will include up to 500 participants at 70 clinical sites, enrolling for 3 years with a minimum of 1-year follow-up. Study candidates include adult patients (age >or= 18 years) with end-stage renal disease who are considered suitable candidates for DHD with the NxStage System One device by the treating physician and who have Medicare as their primary insurance payer. The control group will consist of a matched thrice-weekly in-center HD cohort derived from the US Renal Data System database using a 10:1 ratio, totaling 5,000 patients. PREDICTOR: Treatment with DHD and "standard of care" thrice-weekly HD. OUTCOMES & MEASUREMENTS: The primary intent-to-treat analysis compares hospitalization days/patient-year between the DHD and thrice-weekly HD groups. Other outcomes recorded in both groups include non-treatment-related medical expenditures. In addition, in the DHD cohort, changes in quality-of-life measures (baseline, 4 and 12 months, and every 6 months thereafter); urea kinetics; parameters related to anemia, bone and mineral metabolism, and nutrition; vascular access interventions; and use of medications will be examined. CONCLUSIONS: This study has the potential to elucidate the health and economic benefits of DHD and complement results of current clinical trials.

A time for rediscovery: chronic hemofiltration for end-stage renal disease.

Provision of maintenance renal replacement therapy (MRRT) is becoming increasingly challenging. The number of patients requiring MRRT is growing rapidly, while the number of nephrologists, nurses, and other staff available to provide therapy is not increasing at a similar rate. Patients are now older and have more comorbid conditions, which magnifies the complexity of their RRT and makes it increasingly difficult to maintain the quality of care within the limitations of constrained economic resources. The two most commonly used MRRTs are hemodialysis (HD) and peritoneal dialysis (PD). A third modality of MRRT, hemofiltration, is not currently in widespread use in North America. In hemofiltration, plasma is filtered through a highly permeable, biocompatible synthetic membrane and waste products are removed by convection and solvent drag as the filtrate moves across the membrane. Hemofiltration equipment constantly monitors the rate of plasma removal and administers a sterile, nonpyrogenic replacement solution at an appropriate rate to replace the waste-laden ultrafiltrate and avoid vdume depletion in the patient. Hemofiltration may offer some potential clinical advantages to the MRRT patient, including better hemodynamic and cardiovascular stability, enhanced removal of middle molecular weight toxins, increased comfort, and therapy preference. Some reports indicate possible reduced morbidity and mortality and reduced risk of bacterial contamination and inflammation as a result of the use of sterile, ultrapure replacement fluids. Chronic hemofiltration is a relatively simple MRRT option that may offer significant benefits for many patients who have end-stage renal disease (ESRD) and deserves closer consideration for these patients.

L-carnitine use in dialysis patients: is national coverage for supplementation justified? What were CMS regulators thinking--or were they?

Careful review of all available clinical trials of L-carnitine leads to the conclusion that there is insufficient evidence to support the routine use of L-carnitine for any indication in dialysis patients. The literature suffers from a lack of adequately designed studies, and many of the studies which supposedly justify payment for L-carnitine supplementation are more than 10 years old. While some studies support a subjective improvement in symptoms after a few months of L-carnitine treatment, there is little confirming objective data. Biochemical parameters show minimal, if any, improvements. A major criticism is that many of the reported symptoms could be attributable to anemia, which at the time the L-carnitine studies were taking place, was generally being corrected with EPO. On the other hand, there is little data to support the hypothesis that L-carnitine enhances the response to EPO or overcomes EPO resistance. The decrease in the use of L-carnitine in the past several years may be related in part to difficulty with reimbursement. The decrease also suggests that practitioners have abandoned the hypothesis that L-carnitine supplementation provides substantial clinical benefits, and therefore no longer prescribe it for dialysis patients. For those physicians who plan to prescribe L-carnitine based on the recent CMS reimbursement decision, it must be remembered that the laboratory measurement of free carnitine may be difficult and inaccurate. For those patients with private insurance, payment for the lab test is out of pocket. If the free carnitine level is measured once dialysis starts, a value in the CMS "deficient" range can occur since carnitine drops early in the dialysis procedure and slowly rebounds after the treatment. Therefore, it is critical that the measurement be done pre-dialysis after a three-day interdialytic interval to obtain the most accurate value. If strict guidelines for use of L-carnitine are adhered to (i.e., the patient has true EPO-resistant anemia unexplained by any identifiable factor and true unexplained hypotension), then the use of L-carnitine in ESRD patients should be very uncommon. In conclusion, the clinical value of L-carnitine supplementation in hemodialysis patients remains to be documented by credible evidence from rigorous scientific studies. While "proof beyond a reasonable doubt" need not always be the requirement for reimbursement from payers, at a minimum "a preponderance of the evidence" should be documented in the literature. L-carnitine may prove to be a beneficial supplement. However, before justifying a national coverage policy, a new randomized, prospective controlled trial should be conducted to determine the utility of i.v. L-carnitine supplementation for anemia management and refractory dialysis-associated hypotension. Cost-benefit analysis is a critical aspect of such a study because it is important to determine the total cost (no matter who pays) of L-carnitine supplementation as compared to money saved by a reduction in EPO and iron administration. When reimbursement policies are developed, they need to be rational and based on the best evidence that is available. An NKF Carnitine Consensus Conference concluded that current literature and clinical experience leave unanswered questions regarding the use of L-carnitine in dialysis patients. Until there is scientific evidence to support use of L-carnitine supplementation, and it proves to be cost-effective, reimbursement is not justified. Therefore, the current CMS reimbursement decision for L-carnitine appears to be flawed.