Addressing fluid intake and volume control requires alignment and coordination of patients, providers, dialysis facilities, and payers, potentially necessitating a “Volume First” approach. This ...article reports the consensus opinions achieved at the March 2013 symposium of the Chief Medical Officers of 14 of the largest dialysis providers in the United States. These opinions are based on broad experience among participants, but often reinforced by only observational and frequently retrospective studies, highlighting the lack of high-quality clinical trials in nephrology. Given the high morbidity and mortality rates among dialysis patients and the absence of sufficient trial data to guide most aspects of hemodialysis therapy, participants believed that immediate attempts to improve care based on quality improvement initiatives, physiologic principles, and clinical experiences are warranted until such time as rigorous clinical trial data become available. The following overarching consensus opinions emerged. (1) Extracellular fluid status should be a component of sufficient dialysis, such that approaching normalization of extracellular fluid volume should be a primary goal of dialysis care. (2) Fluid removal should be gradual and dialysis treatment duration should not routinely be less than 4 hours without justification based on individual patient factors. (3) Intradialytic sodium loading should be avoided by incorporating dialysate sodium concentrations set routinely in the range of 134-138 mEq/L, avoidance of routine use of sodium modeling, and avoidance of hypertonic saline solution. (4) Dietary counseling should emphasize sodium avoidance.
Recurrent hemodialysis (HD)-induced ischemic cardiac injury (myocardial stunning) is common and associated with high ultrafiltration (UF) requirements, intradialytic hypotension, long-term loss of ...systolic function, increased likelihood of cardiovascular events, and death. More frequent HD regimens are associated with lower UF requirements and improved hemodynamic tolerability, improved cardiovascular outcomes, and reduced mortality compared with conventional thrice-weekly HD. This study investigated the hypothesis that modification of UF volume and rate with more frequent HD therapies would abrogate dialysis-induced myocardial stunning.
A cross-sectional study of 46 patients established on hemodialysis >3 months compared four groups receiving the current range of quotidian therapies: conventional thrice-weekly HD (CHD3); more-frequent HD five to six times/week in a center (CSD) and at home (HSD); and home nocturnal HD (HN). Serial echocardiography quantitatively assessed regional systolic function to identify intradialytic left ventricular regional wall motion abnormalities (RWMAs). Cardiac troponin T (cTnT), N-terminal prohormone brain natriuretic peptide (NT-proBNP), and inflammatory markers were quantified.
More frequent HD regimens were associated with lower UF volumes and rates compared with CHD3. Intradialytic fall in systolic BP was reduced in CSD and HSD groups and abolished in HN group. Mean RWMAs per patient reduced with increasing dialysis intensity (CHD3 > CSD > HSD > HN). Home-based groups demonstrated lower high-sensitivity C-reative protein levels, with trends to lower cTnT and NT-proBNP levels in the more frequent groups.
Frequent HD regimes are associated with less dialysis-induced myocardial stunning compared with conventional HD. This may contribute to improved outcomes associated with frequent HD therapies.
Abstract Background Intravenous (IV) iron is the treatment of choice for iron-deficiency anemia (IDA) in patients with dialysis-dependent chronic kidney disease (DD-CKD). However, IV iron products ...have been associated with serious adverse events (SAEs), including anaphylactoid reactions. Ferumoxytol is an IV iron preparation that can be injected over a short period of time. Although randomized clinical trials support ferumoxytol’s efficacy and safety, additional insights may be drawn from the acquisition of long-term, repeat dosing efficacy and safety data in a real-world setting. Objective The goal of this study was to characterize the effectiveness and safety profile of ferumoxytol as administered to adult DD-CKD patients with IDA in a real-world setting. The ability of ferumoxytol to maintain hemoglobin (Hb), transferrin saturation (TSAT), and ferritin treatment targets established by the 2006 Kidney Disease Outcomes Quality Initiative guidelines was determined in 3 medium-sized US-based dialysis chains. Methods This retrospective, observational study was conducted to examine laboratory and dosing data for all patients who received any dose of ferumoxytol at 3 US-based dialysis chains over a 12-month period. Investigators and/or physicians from each of the chains also made independent determinations regarding the seriousness of any adverse event (AE). Special attention was paid to the incidence and types of AEs and SAEs that were potentially associated with ferumoxytol. Results Over the 12-month observation period, 8666 patients (mean SD age in chains A, B and C, 63.9 14.8, 63.9 14.9 and 63.6 15.1, respectively), were treated with 33,358 doses of ferumoxytol across the 3 chains. Treatment with ferumoxytol corresponded to an increased mean monthly Hb level relative to baseline (0.13–0.69 g/dL) and led to an increase in the proportion of patients maintained within the target Hb range of 10 to 12 g/dL (61%–72%). Ferumoxytol was also associated with increases in TSAT and ferritin that stabilized throughout the observation period. Incidence of AEs was similar across the 3 chains; between 0.07% and 1.77% of all patients treated at each chain experienced an AE associated with ferumoxytol administration. SAEs were reported in 0.2% of patients. The most common AEs reported (≥6 patients) were nausea (0.37% of patients), pruritus (0.29%), vomiting (0.25%), hypotension (0.21%), and dyspnea (0.20%). Two patients (0.02%) experienced anaphylactoid reactions. The AE profile of ferumoxytol remained consistent with that reported from controlled clinical trials. Conclusions These long-term data, which include repeat dosing in a large number of DD-CKD patients with IDA in a real-world setting, confirm the effectiveness of ferumoxytol in increasing and maintaining Hb levels within the target range and with favorable assessments of long-term safety.
Fluid overload in patients undergoing hemodialysis contributes to cardiovascular morbidity and is a major cause of hospitalizations. It is often addressed by reinforcing the importance of a low-salt ...diet with patients and challenging estimated dry weights. More recently, interest has shifted toward the dialysate sodium prescription as a strategy to improve fluid overload and its adverse sequelae. The availability of high-flux high-efficiency dialysis in conjunction with the need to ensure its tolerability for patients has resulted in an increase in dialysate sodium prescriptions from 120 to ≥140 mEq/L. However, we are now tackling the unforeseen consequences associated with high dialysate sodium prescriptions. High dialysate sodium concentration is associated with high interdialytic weight gain, a commonly used surrogate for hypervolemia contributing to hypertension. The association between mortality and high dialysate sodium concentration remains controversial with conflicting data. It is clear that fluid management in the diverse end-stage renal disease population is extremely complex and more clinical trials are needed. In the meantime, while patients require treatments and clinical decisions need to be made, this review article attempts to summarize the current evidence for individualized dialysate sodium prescriptions based on patients’ volume status, comorbid conditions, plasma sodium level, and hemodynamic response to dialysis therapy.
Background Patients on in-center nocturnal hemodialysis therapy typically experience higher interdialytic weight gain (IDWG) than patients on conventional hemodialysis therapy. We determined the ...safety and effects of decreasing dialysate sodium concentration on IDWG and blood pressure in patients on thrice-weekly in-center nocturnal hemodialysis therapy. Study Design Quality improvement, pre-post intervention. Settings & Participants 15 participants in a single facility. Quality Improvement Plan Participants underwent three 12-week treatment phases, each with different dialysate sodium concentrations, as follows: phase A, 140 mEq/L; phase B, 136 or 134 mEq/L; and phase A+ , 140 mEq/L. Participants were blinded to the exact timing of the intervention. Outcomes IDWG, IDWG/dry weight (IDWG%), and blood pressure. Measurements Outcome data were obtained during the last 2 weeks of each phase and compared with mixed models. The fraction of sessions with adverse events (eg, cramping and hypotension) also was reported. Results IDWG, IDWG%, and predialysis systolic blood pressure decreased significantly by 0.6 ± 0.6 kg, 0.6% ± 0.8%, and 8.3 ± 14.9 mm Hg, respectively, in phase B compared with phase A ( P < 0.05 for all comparisons). No differences in predialysis diastolic and mean arterial or postdialysis blood pressures were found ( P > 0.05 for all comparisons). The proportion of treatments with intradialytic hypotension was low and similar in each phase ( P = 0.9). In phase B compared with phase A, predialysis plasma sodium concentration was unchanged ( P > 0.05), whereas postdialysis plasma sodium concentration decreased by 3.7 ± 1.9 mEq/L ( P < 0.05). Limitations Modest sample size. Conclusion Decreasing dialysate sodium concentrations in patients undergoing thrice-weekly in-center nocturnal hemodialysis resulted in a clinical and statistically significant decrease in IDWG, IDWG%, postdialysis plasma sodium concentration, and predialysis systolic blood pressure without increasing adverse events. Prolonged exposure to higher than required dialysate sodium concentrations may drive IDWG and counteract some of the purported benefits of “go-slow” (longer session length) hemodialysis.
Patients with chronic kidney disease treated by in-center conventional hemodialysis (3 times per week) have significant impairments in health-related quality of life measures, which have been ...associated with increased morbidity and mortality. FREEDOM is an ongoing prospective cohort study measuring the potential benefits of at-home short daily (6 times per week) hemodialysis. In this interim report we examine the long-term effect of short daily hemodialysis on health-related quality of life, as measured by the SF-36 health survey. This was administered at baseline, 4 and 12 months after initiation of short daily hemodialysis to 291 participants (total cohort), of which 154 completed the 12-month follow-up (as-treated cohort). At the time of analysis, the mean age was 53 years, 66% were men, 58% had an AV fistula, 90% transitioned from in-center hemodialysis, and 45% had diabetes mellitus. In the total cohort analysis, both the physical- and mental-component summary scores improved over the 12-month period, as did all 8 individual domains of the SF-36. The as-treated cohort analysis showed similar improvements with the exception of the role-emotional domain. Significantly, in the as-treated cohort, the percentage of patients achieving a physical-component summary score at least equivalent to the general population more than doubled. Hence, at-home short daily hemodialysis is associated with long-term improvements in various physical and mental health-related quality of life measures.
Intravenous iron is a key component of anemia management for chronic kidney disease (CKD). Ferumoxytol is a unique intravenous iron product that can be administered as a rapid injection in doses up ...to 510 mg.
This was a randomized, open-label, controlled, multicenter Phase 3 trial to evaluate the safety and efficacy of intravenous ferumoxytol compared with oral iron. Anemic patients with CKD stage 5D on hemodialysis and on a stable erythropoiesis-stimulating agent regimen received either two injections of 510 mg of ferumoxytol within 7 d (n = 114) or 200 mg elemental oral iron daily for 21 d (n = 116). The primary efficacy endpoint was the change in hemoglobin from baseline to day 35. Safety was closely monitored.
Ferumoxytol resulted in a mean increase in hemoglobin of 1.02 +/- 1.13 g/dl at day 35 compared with 0.46 +/- 1.06 g/dl with oral iron (P = 0.0002). Twice as many ferumoxytol-treated patients than oral iron-treated patients achieved a > or =1 g/dl hemoglobin increase at day 35 (P = 0.0002). There was a greater mean increase in transferrin saturation (TSAT) with ferumoxytol compared with oral iron at day 35 (P < 0.0001). The larger hemoglobin increase after ferumoxytol compared with oral iron at day 35 persisted after adjustment for baseline hemoglobin, TSAT, and serum ferritin. Overall adverse event rates were comparable between groups.
In patients on hemodialysis, rapid intravenous injection of 510 mg of ferumoxytol led to significantly greater hemoglobin increases compared with oral iron, with comparable tolerability.
Background Central venous catheters (CVCs) are used for vascular access in hemodialysis patients who have no alternative access or are awaiting placement or maturation of a permanent access. The ...major complications of CVCs are catheter-related bloodstream infection and clotting in the catheter lumen. Study Design Parallel-group, randomized, multicenter clinical trial, with patients blinded to study intervention. Setting & Participants 16 free-standing dialysis facilities in Northern California belonging to a single provider. 303 adult maintenance hemodialysis patients who were using a tunneled cuffed CVC for vascular access. Intervention The treatment group received an antibiotic lock containing gentamicin 320 μg/mL in 4% sodium citrate, whereas the control group received the standard catheter lock containing heparin 1,000 U/mL. Both groups received triple-antibiotic ointment on the catheter exit site during dressing changes at each dialysis treatment. Outcomes Catheter-related bloodstream infection and catheter clotting. Measurements Catheter-related bloodstream infection was defined as the occurrence of symptoms consistent with bacteremia together with positive blood culture results in the absence of another obvious source of infection. Catheter clotting was measured as the rate of thrombolytic agent use required to maintain adequate blood flow. A single patient could contribute more than one infection or clotting episode. Results The rate of catheter-related bloodstream infection was 0.91 episodes/1,000 catheter-days in the control group and 0.28 episodes/1,000 catheter-days in the treatment group ( P = 0.003). The time to the first episode of bacteremia was significantly delayed ( P = 0.005). The rates of tissue plasminogen activator use were similar in the treatment and control groups: 2.36 versus 3.42 events/1,000 catheter-days, respectively ( P = 0.2). Limitations The requirement for dialysis facility staff to prepare the treatment intervention prevented a completely blinded study. Conclusion Gentamicin 320 μg/mL in 4% sodium citrate used as a routine catheter lock in CVCs in patients on maintenance hemodialysis therapy markedly decreases the incidence of catheter-related bloodstream infection and is as effective as heparin 1,000 U/mL in preventing catheter clotting.
Restless legs syndrome (RLS) and sleep disturbances are common among in-center hemodialysis patients and are associated with increased morbidity/mortality.
The FREEDOM study is an ongoing prospective ...cohort study investigating the benefits of home short daily hemodialysis (SDHD) (6 times/week). In this interim report, we examine the long-term effect of SDHD on the prevalence and severity of RLS, as measured by the International Restless Legs Syndrome (IRLS) Study Group rating scale, and sleep disturbances, as measured by the Medical Outcomes Study sleep survey.
235 participants were included in this report (intention-to-treat cohort), of which 127 completed the 12-month follow-up (per-protocol cohort). Mean age was 52 years, 55% had an arteriovenous fistula, and 40% suffered from RLS. In the per-protocol analysis, among patients with RLS, the mean IRLS score improved significantly at month 12, after adjustment for use of RLS-related medications (18 versus 11). Among patients with moderate-to-severe RLS (IRLS score ≥15), there was an even greater improvement in the IRLS score (23 versus 13). The intention-to-treat analysis yielded similar results. Over 12 months, there was decline in the percentage of patients reporting RLS (35% versus 26%) and those reporting moderate-to-severe RLS (59% versus 43%). There was a similar and sustained 12-month improvement in several scales of the sleep survey, after adjustment for presence of RLS and use of anxiolytics and hypnotics.
Home SDHD is associated with long-term improvement in the prevalence and severity of RLS and sleep disturbances.
People with end-stage kidney disease receiving peritoneal dialysis (PD) are generally physically inactive and frail. Exercise studies in PD are scarce and currently there are no PD exercise programs ...in the United States. The primary objective of this study was to test the feasibility of a combined resistance and cardiovascular exercise program for PD patients under the care of a dedicated home dialysis center in the United States.
Parallel randomized controlled feasibility study.
PD patients were recruited from a single center and randomly assigned to the intervention (exercise; n = 18) or control (nonexercise; n = 18) group.
The intervention group received monthly exercise physiologist consultation, exercise prescription (resistance and aerobic exercise program using exercise bands), and 4 exercise support telephone calls over 12 weeks. The control group received standard care.
The primary outcome was study feasibility as measured by eligibility rates, recruitment rates, retention rates, adherence rates, adverse events, and sustained exercise rates. Secondary outcome measures were changes in physical function (sit-to-stand test, timed-up-and-go test, and pinch-strength tests) and patient-reported outcome measures.
From a single center with 75 PD patients, 57 (76%) were deemed eligible, resulting in a recruitment rate of 36 (63%) patients. Participants were randomly assigned into 2 groups of 18 (1:1). 10 patients discontinued the study (5 in each arm), resulting in 26 (72%) patients, 13 in each arm, completing the study. 10 of 13 (77%) intervention patients were adherent to the exercise program. A t test analysis of covariance found a difference between the treatment groups for the timed-up-and-go test (P = 0.04) and appetite (P = 0.04). No serious adverse events caused by the exercise program were reported.
Single center, no blinded assessors.
A resistance and cardiovascular exercise program appears feasible and safe for PD patients. We recommend that providers of PD therapy consider including exercise programs coordinated by exercise professionals to reduce the physical deterioration of PD patients.
None.
NCT03980795.
Display omitted
PDF
