Using dalteparin in quotidian and nocturnal hemodialysis patients: A prospective study.

INTRODUCTION: Low-molecular weight heparin, such as dalteparin, is an alternative anticoagulation method in conventional hemodialysis (HD). However, there are limited studies on its use in quotidian and nocturnal HD. We assessed the optimal dose, treatment efficacy, and patient safety of dalteparin in quotidian and nocturnal HD populations. METHODS: This study included 10 quotidian (7 in-center and 3 home) and 8 nocturnal home HD patients. Dalteparin was initiated and titrated based on clotting score in these patients. Trough anti-Xa levels were measured. The dalteparin dose, the dialyzer and HD circuit clotting scores, and bleeding episodes were recorded at 4 weeks. Patients who continued dalteparin were followed to 12 months. FINDINGS: For the 10 quotidian HD patients, the median dalteparin dose was 1875 units [1250, 2500] after 4 weeks. For nocturnal HD patients, five of the eight patients switched back to heparin due to high clotting scores while on dalteparin within 4 weeks. However, three patients continued on dalteparin at 4 weeks. After 12 months, one maintained on 5000 units and the other two maintained on 7500 units of dalteparin. All the clotting scores at month 12 were ≤2. One patient died due to an unrelated cause. For all patients who continued on dalteparin, only 9% of the HD treatments had circuit clotting score >2 after reaching stable dose. All trough anti-Xa levels were <0.1 IU/mL. There were no episodes of bleeding. Fistula compression times were not increased. DISCUSSION: This small pilot study suggests that dalteparin can be used effectively and relatively safety in quotidian HD. However, its use in nocturnal HD was only successful in a small proportion of patients. Alternative methods, including second dalteparin bolus after 4 hours of HD treatment, should be assessed for efficacy and practicality.

The effect of increased frequency of hemodialysis on serum cystatin C and ß2-microglobulin concentrations: A secondary analysis of the frequent hemodialysis network (FHN) trial.

INTRODUCTION: Small molecular weight toxin clearance is the main method of assessment of hemodialysis efficiency. Middle molecules including cystatin C (CysC) and Beta-2 microglobulin (ß2-M) are understudied. We hypothesized that lowering of predialysis CysC and ß2-M serum concentrations would be affected by switching to more frequent hemodialysis. METHODS: Predialysis CysC and ß2-M serum concentrations were measured from serum samples of the Frequent Hemodialysis Network (FHN) Daily and Nocturnal Trials. The differences between predialysis concentrations at baseline (while on conventional thrice weekly dialysis) and those after 12-months of study (on more frequent dialysis) were compared separately by trial (Nocturnal, Daily). We tested the associations between predialysis serum CysC and ß2-M concentrations and outcomes. FINDINGS: Forty-nine percent and 52% of the patients from the FHN Daily and Nocturnal Trials respectively were included in this ancillary study. Predialysis serum CysC concentrations remained unchanged after intensifying hemodialysis dose by either modality. There was significant lowering of the serum ß2-M concentrations in the frequent Daily Trial hemodialysis group at 12 months in all patients and in patients without residual renal function at baseline (-3.8 ± 12.62 µg/mL, P = 0.004; -5.9 ± 12.99 µg/mL, P = 0.02, respectively). There were no significant differences between the baseline and the 12-months predialysis ß2-M serum concentrations in the two control groups (Daily 3× and Nocturnal 3× groups). No association between the changes in the two biomarkers between baseline and 12-months and in changes in left ventricular mass, physical-health composite scores, hospitalization rate, and death were found. The numbers of hospitalizations and deaths were small. DISCUSSION: ß2-M may be a better biomarker of dialysis dose than CysC. Reduction in the concentration of potentially toxic long-lived proteins of the size of ß-2M is one potential long-term benefit of more intensive dialysis that may be explored.

In-center hemodialysis education: Challenges and innovations in training of fellows in nephrology.

The in-center dialysis unit and practice of dialysis, in the current multi-team approach, requires knowledge and skills in all the domains including medical expert, communicator, collaborator, scholar, health advocate, and leader. We are tasked as a community, to embrace and incentivize new innovations and technology to address these needs for our post graduate trainees. These innovations must address the basic principles of dialysis, quality improvement, technical and procedural skills as well as leadership and administration skills. The teaching methods and innovations must also be challenged to demonstrate the translation into adoption and improvements in practice to demonstrate success. This article will review the current state of the training curriculum in Nephrology for in-center hemodialysis and address some of the recent innovations.

Patients receiving frequent hemodialysis have better health-related quality of life compared to patients receiving conventional hemodialysis.

Most patients with end-stage kidney disease value their health-related quality of life (HRQoL) and want to know how it will be affected by their dialysis modality. We extended the findings of two prior clinical trial reports to estimate the effects of frequent compared to conventional hemodialysis on additional measures of HRQoL. The Daily Trial randomly assigned 245 patients to receive frequent (six times per week) or conventional (three times per week) in-center hemodialysis. The Nocturnal Trial randomly assigned 87 patients to receive frequent nocturnal (six times per week) or conventional (three times per week) home hemodialysis. All patients were on conventional hemodialysis prior to randomization, with an average feeling thermometer score of 70 to 75 (a visual analog scale from 0 to 100 where 100 is perfect health), an average general health scale score of 40 to 47 (a score from 0 to 100 where 100 is perfect health), and an average dialysis session recovery time of 2 to 3 hours. Outcomes are reported as the between-treatment group differences in one-year change in HRQoL measures and analyzed using linear mixed effects models. After one year in the Daily Trial, patients assigned to frequent in-center hemodialysis reported a higher feeling thermometer score, better general health, and a shorter recovery time after a dialysis session compared to standard thrice-weekly dialysis. After one year in the Nocturnal Trial, patients assigned to frequent home hemodialysis also reported a shorter recovery time after a dialysis session, but no statistical difference in their feeling thermometer or general health scores compared to standard home dialysis schedules. Thus, patients receiving day or nocturnal hemodialysis on average recovered approximately one hour earlier from a frequent compared to conventional hemodialysis session. Patients treated in an in-center dialysis facility reported better HRQoL with frequent compared to conventional hemodialysis.

Can the new CKD-EPI BTP-B2M formula be applied in children?

Although measuring creatinine to determine kidney function is currently the clinical standard, new markers such as beta-trace protein (BTP) and beta-2-microglobulin (B2M) are being investigated in an effort to measure glomerular filtration rate more accurately. In their recent publication, Inker et al. (Am J Kidney Dis 2015; 67:40-48) explored the use of these two relatively new markers in combination with some commonly available clinical characteristics in a large cohort of adults with chronic kidney disease. Their research led them to develop three formulae using BTP, B2M, and a combination of the two. The combined formula is particularly attractive as it removes all gender bias, which applies to both serum creatinine and cystatin C. Using data from a cohort of 127 pediatric patients from our center, we sought to determine whether these formulae would be equally as effective in children as in adults. Unfortunately, we found that the formulae cannot be applied to the pediatric population.

The choice of dialysate sodium is influenced by hemodialysis frequency and duration: what should it be and for what modality?

Cardiovascular disease is the leading cause of mortality in hemodialysis patients. A chronic state of volume and pressure overload contributes, and central to this is the net sodium balance over the course of a hemodialysis. Of recent interest is the contribution of the dialysate sodium concentration (Dial-Na+) to clinical outcomes. Abundant evidence confirms that in thrice-weekly conventional hemodialysis, higher Dial-Na+ associates with increased intradialytic weight gain, blood pressure, and cardiovascular morbidity and mortality. On the other hand, low Dial-Na+ associates with intradialytic hypotension in the same patient population. However, the effect of Dial-Na+ in short hours daily hemodialysis (SHD; often referred to as "quotidian" dialysis), or nocturnal dialysis (FHND) is less well studied. Increased frequency and duration of exposure to a diffusive sodium gradient modulate the way in which DPNa+ alters interdialytic weight gain, predialysis blood pressure, and intradialytic change in blood pressure. Furthermore, increased dialysis frequency appears to decrease the predialysis plasma sodium setpoint (SP), which is considered stable in conventional thrice-weekly patients. This review discusses criteria to determine optimal Dial-Na+ in conventional, SHD and FHND patients, and identifies areas for future research.

What is single needle cannulation hemodialysis: is it adequate?

BACKGROUND: It is important to know the relative clearances obtained when using single-needle versus double-needle cannulation techniques. METHOD: Twelve hemodialysis treatments were conducted using a machine that is capable of single-needle as well as double-needle cannulation. Single-needle and double-needle blood flow rates, as well as urea clearance, were compared. RESULTS: The measured blood flow rates were 368 ± 11 ml/min, 294 ± 4 ml/min, 200 ± 0 ml/min, and 100 ± 0 ml/min during double-needle hemodialysis and were 201 ± 10.9 ml/min, 173 ± 44.9 ml/min, 103 ± 4.1 ml/min, and 45 ± 4.9 ml/min during single-needle hemodialysis. The hemodialysis urea clearances at similar blood flow rate (approximately 200 ml/min) were 167 ± 4 ml/min and 161 ± 9 ml/min (paired t test; p > 0.05), respectively. CONCLUSION: The measured blood flow rates and urea clearances during single-needle hemodialysis were approximately half of the measured blood flow rate during double-needle hemodialysis, and should be used in selected settings.

Nocturnal home hemodialysis associates with improvement of electrocardiographic features linked to sudden cardiac death.

Sudden cardiac death (SCD) remains the leading cause of death in hemodialysis patients. We performed a retrospective electrocardiograph (ECG) and chart review to determine whether hemodialysis modality, frequency, or duration could predict change in ECG parameters associated with SCD. Frequent nocturnal hemodialysis was associated with an improvement in Tpeak to Tend within 365 days (83.8-71.8 ms, p = 0.005) and past 365 days of dialysis initiation (85.9-77.1 ms, p = 0.005) and improvement in QRS amplitude variation within 365 days (0.0583-0.0297, p = 0.025) and past 365 days of dialysis initiation (0.0546-0.0332, p = 0.029). Compared with intermittent conventional hemodialysis, more frequent nocturnal (15/25 vs. 3/14, p = 0.04) and intermittent nocturnal hemodialysis (INHD) (6/8 vs. 3/14, p = 0.03) patients decreased Tpeak to Tend. More short-hours daily than INHD patients increased T-wave amplitude variation (16/25 vs. 1/8, p = 0.02). These improvements occurred before changes in Cornell or Sokolow-Lyon electrocardiographic left ventricular mass. Thus, it appears that hemodialysis modalities of longer duration are associated with improvements in electrocardiographic parameters associated with SCD. Prospective trials are required to determine whether dialysis prescription reduces SCD, cardiovascular morbidity, and mortality in hemodialysis patients.

Plasma sodium setpoint: is it constant or changed by hemodialysis prescription?

Stability of predialysis sodium "setpoint" has not been validated in quotidian dialysis patients. We performed a retrospective review of our home hemodialysis program, to determine the effect of transitioning from conventional thrice weekly to home hemodialysis modalities differing in dialysis duration and frequency (n = 87). Mean sodium setpoint remained constant in patients who went home on intermittent hemodialysis, but decreased by 100 days in frequent nocturnal home hemodialysis (FNHD) (140.5-137.1 mM, p = 0.001) and short hours daily hemodialysis (SHD) (140.2-138.7 mM, p = 0.019) patients with a pretransition setpoint greater than dialysate sodium of 140 mM. Slope of predialysis sodium concentration within the first 100 days post-transition (M100) was less than zero in SHD (95% confidence interval [CI], -0.0081 to -0.0351 mM/day) and FNHD (95% CI, -0.0209 to -0.0695 mM/day) patients who started with a pretransition setpoint greater than dialysate sodium concentration of 140 mM. Change in sodium setpoint (SP) was predicted by dialysis frequency and the difference between dialysate sodium concentration and the pretransition predialysis sodium concentration (R = 35.4%, adjusted R = 33.8%, p < 0.001). Thus, personalizing dialysate sodium concentrations may be associated with a decrease in SP, which is independently associated with increased mortality. Further research is required to determine whether intentional increases in the SP could improve cardiovascular and all-cause mortality.

Frequent nocturnal hemodialysis associates with improvement of prolonged QTc intervals.

BACKGROUND/AIMS: Sudden cardiac death remains the leading cause of death in hemodialysis (HD) patients. Prolongation of QTc intervals (as measured by the tangent method) increases sudden cardiac death risk in populations without kidney disease. METHODS: We performed a retrospective electrocardiograph (ECG) and chart review of HD patients. Our objectives were (1) to establish the effect of one of four different dialysis modalities on interdialytic QTc intervals, (2) to determine the effect of dialysis frequency and time on QTc interval and on the prevalence of borderline or prolonged QTc intervals, and (3) to determine if changes in QTc interval were simultaneous to changes in electrocardiographic left ventricular mass. RESULTS: Frequent nocturnal HD was associated with a decrease in QTc interval for all patients (from 436.5 to 421.3 ms, p = 0.0187) and for patients who initiated dialysis with prolonged QTc (468.2 to 438.2 ms, p = 0.0134). This change happened before changes in left ventricular mass were evident. Dialysis duration predicted a decrease in QTc better than dialysis frequency (R(2) 6.50 vs. 3.00%, p = 0.023 vs. 0.102). Prevalence of borderline or prolonged QTc increased in patients dialyzed <4 h/session (12/39 to 22/39, p = 0.039). CONCLUSIONS: Frequent nocturnal HD may be the ideal modality to initiate HD in end-stage kidney disease patients with prolonged QTc.

Modifiable variables affecting interdialytic weight gain include dialysis time, frequency, and dialysate sodium.

Interdialytic weight gain (IDWG) is associated with hypertension, left ventricular hypertrophy, and all-cause mortality. Dialysate sodium concentration may cause diffusion gradients with plasma sodium and influence subsequent IDWG. Dialysis time and frequency may also influence the outcomes of this Na(+) gradient; these have been overlooked. Our objective was to identify modifiable factors influencing IDWG. We performed a retrospective multivariable regression analyses of data from 86 home hemodialysis patients treated by hemodialysis modalities differing in frequency and session duration to determine factors involved that predict IDWG. Age, diabetic status, and residual renal function did not correlate with IDWG in the univariable analysis. However, using a combination of backwards selection and Akaike information criterion to build our model, we created an equation that predicted IDWG on the basis of serum albumin, age, patient sex, dialysis frequency, and the diffusive balance of sodium, represented by the product of the duration of dialysis and the patient plasma to dialysate Na(+) gradient. This equation was internally validated using bootstrapping, and externally validated in a temporally distinct patient population. We have created an equation to predict IDWG on the basis of independent factors readily available before a dialysis session. The modifiable factors include dialysis time and frequency, and dialysate sodium. Patient sex, age, and serum albumin are also correlated with IDWG. Further work is required to establish how improvements in IDWG influence cardiovascular and other clinical outcomes.

Pre to post-dialysis plasma sodium change better predicts clinical outcomes than dialysate to plasma sodium gradient in quotidian hemodialysis.

Sodium balance across a hemodialysis treatment influences interdialytic weight gain (IDWG), pre-dialysis blood pressure, and the occurrence of intradialytic hypotension, which associate with patient morbidity and mortality. In thrice weekly conventional hemodialysis patients, the dialysate sodium minus pre-dialysis plasma sodium concentration (δDPNa+) and the post-dialysis minus pre-dialysis plasma sodium (δPNa+) are surrogates of sodium balance, and are associated with both cardiovascular and all-cause mortality. However, whether δDPNa+ or δPNa+ better predicts clinical outcomes in quotidian dialysis is unknown. We performed a retrospective analysis of clinical and demographic data from the Southwestern Ontario Regional Home Hemodialysis program, of all patients since 1985. In frequent nocturnal hemodialysis, δPNa+ was superior to δDPNa+ in predicting IDWG (R(2)=0.223 vs. 0.020, P=0.002 vs. 0.76), intradialytic change in systolic (R(2)=0.100 vs. 0.002, P=0.02 vs. 0.16) and diastolic (R(2)=0.066 vs. 0.019, P=0.02 vs. 0.06) blood pressure, and ultrafiltration rate (R(2)=0.296 vs. 0.036, P=0.001 vs. 0.52). In short hours daily hemodialysis, δDPNa+ was better than δPNa+ in predicting intradialytic change in diastolic blood pressure (R(2)=0.101 vs. 0.003, P=0.02 vs. 0.13). However, δPNa+ was better than δDPNa+ in predicting IDWG (R(2)=0.105 vs. 0.019, P=0.04 vs. 0.68) and pre-dialysis systolic blood pressure (R(2)=0.103 vs. 0.007, P=0.02 vs. 0.82). We also found that the intradialytic blood pressure fall was greater in frequent nocturnal hemodialysis patients than in short hours daily patients, when exposed to a dialysate to plasma sodium gradient. These results provide a basis for design of prospective trials in quotidian dialysis modalities, to determine the effect of sodium balance on cardiovascular outcome.

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.

A multinational cohort study of in-center daily hemodialysis and patient survival.

Increasing hemodialysis frequency from three to six times per week improves left-ventricular mass and health-related quality of life; however, effects on survival remain uncertain. To study this, we identified 556 patients in the International Quotidian Dialysis Registry who received daily hemodialysis (more than five times per week) between 2001 and 2010. Using propensity score-based matching, we matched 318 of these patients to 575 contemporaneous patients receiving conventional (three times weekly) hemodialysis in the Dialysis Outcomes and Practice Patterns Study. All patients had session times of <5 h, and received dialysis in the clinic or hospital setting. Mortality rates between groups were compared using Cox proportional hazards regression. Mean dialysis frequency in the daily group was 5.8 sessions per week. Mean weekly treatment time was 15.7 h for daily and 11.9 h for conventional patients. During 1382 patient-years of follow-up, 170 patients died. Those receiving daily hemodialysis had a significantly higher mortality rate than those receiving conventional hemodialysis (15.6 and 10.9 deaths per 100 patient-years, respectively: hazard ratio 1.6). Similar results were found in prespecified subgroup and sensitivity analyses. Unlike previous studies, we found that in-center daily hemodialysis was not associated with any mortality benefit. Thus, decisions to undertake daily hemodialysis should be based on quality-of-life improvements, rather than on claims of improved survival.

Biofeedback dialysis for hypotension and hypervolemia: a systematic review and meta-analysis.

BACKGROUND: Intradialytic hypotension (IDH) is associated with morbidity and mortality. We conducted a systematic review to determine whether biofeedback hemodialysis (HD) can improve IDH and other outcomes, compared with HD without biofeedback. METHODS: Data sources included the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and ISI Web of Science. We included randomized trials that enrolled adult patients (>18 years) with IDH or extracellular fluid expansion and that used biofeedback to guide ultrafiltration and/or dialysate conductivity. Two authors assessed trial quality and independently extracted data in duplicate. We assessed heterogeneity using I(2). We applied the GRADE framework for rating the quality of evidence. RESULTS: We found two parallel-arm randomized controlled clinical trials and six randomized crossover trials meeting inclusion criteria. All trials were open-label and at least four were industry-sponsored. Studies were small (median n = 27). No study evaluated hospitalization and the evidence for effect on mortality was of very low quality. Three studies assessed quality of life (QoL); none demonstrated benefit or harm, and quality of evidence was very low. Biofeedback significantly reduced IDH (risk ratio 0.61, 95% confidence interval 0.44-0.86; I(2)= 0%). Quality of evidence for this outcome was low due to risk of bias and potential publication bias. CONCLUSIONS: Biofeedback dialysis significantly reduces the frequency of IDH. Large and well-designed randomized trials are needed to assess the effects on survival, hospitalization and QoL.

Dialysis search filters for PubMed, Ovid MEDLINE, and Embase databases.

BACKGROUND AND OBJECTIVES: Physicians frequently search bibliographic databases, such as MEDLINE via PubMed, for best evidence for patient care. The objective of this study was to develop and test search filters to help physicians efficiently retrieve literature related to dialysis (hemodialysis or peritoneal dialysis) from all other articles indexed in PubMed, Ovid MEDLINE, and Embase. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A diagnostic test assessment framework was used to develop and test robust dialysis filters. The reference standard was a manual review of the full texts of 22,992 articles from 39 journals to determine whether each article contained dialysis information. Next, 1,623,728 unique search filters were developed, and their ability to retrieve relevant articles was evaluated. RESULTS: The high-performance dialysis filters consisted of up to 65 search terms in combination. These terms included the words "dialy" (truncated), "uremic," "catheters," and "renal transplant wait list." These filters reached peak sensitivities of 98.6% and specificities of 98.5%. The filters' performance remained robust in an independent validation subset of articles. CONCLUSIONS: These empirically derived and validated high-performance search filters should enable physicians to effectively retrieve dialysis information from PubMed, Ovid MEDLINE, and Embase.