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 (R² = 0.223 vs. 0.020, P = 0.002 vs. 0.76), intradialytic change in systolic (R² = 0.100 vs. 0.002, P = 0.02 vs. 0.16) and diastolic (R² = 0.066 vs. 0.019, P = 0.02 vs. 0.06) blood pressure, and ultrafiltration rate (R² = 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 (R² = 0.101 vs. 0.003, P = 0.02 vs. 0.13). However, δPNa+ was better than δDPNa+ in predicting IDWG (R² = 0.105 vs. 0.019, P = 0.04 vs. 0.68) and pre‐dialysis systolic blood pressure (R² = 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.     

Effect of the decrease in dialysate sodium in pediatric patients on chronic hemodialysis

Optimal dialysate sodium (dNa) is unknown, with both higher and lower values suggested in adult studies to improve outcomes. Similar studies in pediatric hemodialysis (HD) population are missing. This is the first report of the effect of two constant dNa concentrations in pediatric patients on chronic HD. 480 standard HD sessions and interdialytic periods were studied in 5 patients (age 4–17 years, weight 20.8–66 kg) during a period of 6–11 months per patient. dNa was 140 mEq/L during the first half, and 138 mEq/L during the second half of the study period for each patient. Lowering dNa was associated with improved preHD hypertension, decreased interdialytic weight gain, decreased need for ultrafiltration, lower sodium gradient and was well tolerated despite lack of concordance with predialysis sNa, that was variable. Further studies are needed to verify our findings and to investigate if an even lower dNa may be more beneficial in the pediatric HD population.     

Sodium and ultrafiltration profiling in hemodialysis: A long-forgotten issue revisited

Sodium and ultrafiltration profiling are method of dialysis in which dialysate sodium concentration and ultrafiltration rate are altered during the course of the dialysis session. Sodium and ultrafiltration profiling have been used, commonly simultaneously, to improve hemodynamic stability during hemodialysis. Sodium profiling is particularly effective in decreasing the incidence of intradialytic hypotension, while ultrafiltration profiling is suggested to decrease subclinical repeated end organ ischemia during dialysis. However, complications such as increased interdialytic weight gain and thirst due to sodium excess have prevented widespread use of sodium profiling. Evidence suggest that different sodium profiling techniques may lead to different clinical results, and preferring sodium balance neutral sodium profiling may mitigate adverse effects related to sodium overload. However, evidence is lacking on the long-term clinical outcomes of different sodium profiling methods. Optimal method of sodium profiling as well as the utility of sodium/ultrafiltration profiling in routine practice await further clinical investigation.     

Effects of citrate‐enriched bicarbonate based dialysate on anticoagulation and dialyzer reuse in maintenance hemodialysis patients

Systemic anticoagulation with unfractionated heparin is commonly used in maintenance hemodialysis (HD), but it increases the risk of bleeding complications. We investigated whether the use of citrate‐enriched bicarbonate based dialysate (CD) would reduce systemic anticoagulation without compromising the efficacy of reprocessed dialyzers. This is a crossover study in which half of a total of 30 patients initially underwent HD with acetate‐enriched bicarbonate based dialysate and a standard heparin dose of ～100 IU/kg (Treatment A), whereas the remaining patients were treated with CD and a 30% reduced heparin dose (Treatment B). After 12 consecutive HD sessions in each treatment, the dialysate and heparin doses were reversed, then followed for another period of 12 HD sessions. The two treatment phases were split by a washout period of six HD sessions using acetate‐enriched bicarbonate based dialysate and standard heparin dose. Systemic anticoagulation was higher in Treatment A. The activated partial thromboplastin time at the end of HD session was 68 ± 36 seconds in Treatment A and 47 ± 16 seconds in Treatment B (P = 0.005). Sixty‐eight percent of the dialyzers remained adequate until the 12th use in Treatment A and 61% did so in Treatment B (P = 0.63). Patients had three and 24 cramps episodes during Treatment A and B, respectively (P < 0.001). Nine and 26 symptomatic intradialytic hypotension episodes were seen in Treatment A and B, respectively, (P = 0.003). In conclusion, the use of CD had a favorable effect on anticoagulation in the extracorporeal circuit in patients on maintenance HD, but it was also associated with more hypotension and cramps.     

Understanding barriers to home‐based and self‐care in‐center hemodialysis

Despite superior outcomes and lower associated costs, relatively few patients with end‐stage renal disease undergo self‐care or home hemodialysis. Few studies have examined patient‐ and physician‐specific barriers to self‐care and home hemodialysis in the modern era. The degree to which innovative technology might facilitate the adoption of these modalities is unknown. We surveyed 250 patients receiving in‐center hemodialysis and 51 board‐certified nephrologists to identify key barriers to adoption of self‐care and home hemodialysis. Overall, 172 (69%) patients reported that they were “likely” or “very likely” to consider self‐care hemodialysis if they were properly trained on a new hemodialysis system designed for self‐care or home use. Nephrologists believed that patients were capable of performing many dialysis‐relevant tasks, including: weighing themselves (98%), wiping down the chair and machine (84%), clearing alarms during treatment (53%), taking vital signs (46%), and cannulating vascular access (41%), but thought that patients would be willing to do the same in only 69%, 34%, 31%, 29%, and 16%, respectively. Reasons that nephrologists believe patients are hesitant to pursue self‐care or home hemodialysis do not correspond in parallel or by priority to reasons reported by patients. Self‐care and home hemodialysis offer several advantages to patients and dialysis providers. Overcoming real and perceived barriers with new technology, education and coordinated care will be required for these modalities to gain traction in the coming years.     

Sleep apnea in hemodialysis patients: risk factors and effect on survival

Sleep disorders are common in patients with end-stage renal disease (ESRD). Using a simple questionnaire, we estimate the probability of sleep apnea in ESRD patients, determine the factors associated with a higher probability of sleep apnea, and determine the association between the probability of sleep apnea and cardiovascular and all-cause mortality. Study design: Prospective cohort study. Setting and participants: prevalent hemodialysis patients (n=270) in 7 urban outpatient hemodialysis units. Predictor: Probability of sleep apnea as quantified by the Flemons questionnaire. Outcomes and measurements: Clinical, demographic, and dialysis-related characteristics were obtained at baseline. Total and cardiovascular mortality was ascertained after a median follow-up of 34 months. The probability of sleep apnea was low in 79 (29%) patients, moderate in 116 (43%) patients, and high in 75 (28%) patients. Male gender (odds ratio [OR] 5.13, p<0.001), obesity (BMI >30, OR 7.58, p<0.01), and interdialytic weight gain (OR 1.72/kg change, p<0.004) were independently associated with a high probability of sleep apnea. A high probability of sleep apnea at baseline did not predict total (hazard ratio [HR] 0.81, p=NS) or cardiovascular mortality (HR 0.9, p=NS). The Flemons questionnaire is validated in the general population, but has not been tested specifically in hemodialysis patients. The study may not be adequately powered to detect a difference in mortality. A high proportion of hemodialysis patients are likely to have sleep apnea; a simple bedside questionnaire can be used for screening to identify these patients. Excessive interdialytic weight gain is a potentially modifiable factor that increases the likelihood of sleep apnea. Despite the presence of a strong association between sleep apnea and mortality in the general population, a similar association could not be demonstrated in ESRD patients with a high prevalence of this condition.     

Residual renal function and arterial stiffness mediated the blood pressure change during interdialytic weight gain in hemodialysis patients

Volume overload is thought to be the main cause of hypertension in dialysis patients. However, the effect of interdialytic weight gain (IDWG) in hemodialysis (HD) patients, which was considered as an increase in extracellular water (ECW), on blood pressure (BP) change, was controversial. Our aim was to examine the changes in hemodynamics and arterial stiffness during IDWG in HD patients and attempt to explore the possible mechanism of diverse BP change. Thirty prevalent patients on HD were enrolled. The height, weight, BP, blood chemistry, volume status assessed by bioelectrical impedance analysis, hemodynamic parameters obtained by echocardiography, and pulse wave velocity (PWV) were collected within 1 hour postdialysis and again just before the next dialysis session. Meanwhile, blood samples were drawn to analyze vasoactive hormones, including renin, angiotensin II, catecholamine, and endothelin. The patients' weights and ECWs during the next predialysis were significantly higher than those during the postdialysis. The BP showed no difference between postdialysis and the next predialysis. There was an obvious increase in cardiac output and decrease in total peripheral resistance as a whole during the next predialysis than that during postdialysis. When patients were divided into the BP increase group (BPI group, 13 patients) and BP decrease group (BPD group, 11 patients) according to the change in systolic BP higher than 10 mmHg, both groups displayed a significant increase in weight, ECW, cardiac output, and a decrease in total peripheral resistance. As compared with the BPI group, patients in the BPD group had significantly lower IDWG, shorter time on dialysis treatment, and higher residual renal function. A decrease in catecholamine and endothelin in the next predialysis was obvious in the BPD group. There was a significant decrease in PWV at the next predialysis in the BPD group while the PWV did not change significantly in the BPI group. Our results showed that the diverse BP change during IDWG was significantly affected by residual renal function, PWV, and vasoactive substances.     

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.     

High sodium continuous veno‐venous hemodialysis with regional citrate anticoagulation and online dialysate generation in patients with acute liver failure and cerebral edema

Introduction: Acute liver failure is associated with a high mortality rate. Induction of plasma hypertonicity with mannitol or hypertonic saline remains the cornerstone in the management of resultant cerebral edema. Significant disadvantages of this approach include poor or unpredictable control of serum sodium concentration and volume expansion, among others. Methods: We used high sodium continuous veno‐venous hemodialysis with regional citrate anticoagulation and online dialysate generation to accurately control the serum sodium in eleven patients with acute liver failure, renal failure, and cerebral edema. We used a Fresenius 2008 K/K2 machine in hemodialysis mode to deliver a blood flow of 60 ml/minute and dialysate flow of 400 ml/minute. Our previously published protocol results in complete removal of infused citrate by the dialyzer. On‐line clearance calculations were used to model the time required to reach the target serum sodium. Findings: All patients achieved serum sodium within 2 mEq/L of target without fluctuations or rebound. Nine patients survived without requiring liver transplantation and two died despite reaching the prescribed serum sodium target. We did not encounter any citrate toxicity. Discussion: We describe a novel approach for delivering continuous osmotherapy to patients with acute liver failure, renal failure, and cerebral edema. In comparison to standard therapy, the described modality enables precise titration of serum sodium without undesirable fluctuations in extracellular fluid volume. A particular advantage is zero delivery of citrate to this vulnerable group of patients with acute liver failure.     

A Composite Index of Compliance for Chronic In‐Center Hemodialysis Patients

We developed a composite compliance index as the sum of the compliance scores for interdialytic weight gain (IDWG), pre‐dialysis serum potassium and phosphorus concentrations (each scored from zero to 3, with 3 indicating the poorest compliance), and skipping hemodialysis sessions (scored from zero to 9, with 9 indicating the poorest compliance). We used this composite score to prospectively evaluate compliance in 25 prevalent hemodialysis patients over a period of 1 year. We then followed these patients for another 3.5 years. The patients studied were divided into two groups: group A (poor compliance) consisted of 9 subjects with composite score ≥ 9 (13.2 ± 3.2); group B (better compliance) consisted of 16 subjects with composite score < 9 (4.7 ± 1.8). Age, duration of hemodialysis, and frequency of diabetes mellitus did not differ between the groups. Group A contained higher fractions of subjects with history of alcoholism (66.7% vs 12.5%, p = 0.010), other substance addiction (44.4% vs 0%, p = 0.010), and severe psychosocial problems (88.9% vs 18.8%, p = 0.002). Mean survival from the beginning of observation, estimated by actuarial life‐table survival analysis, was 1.19 years in group A and 2.60 years in group B (p = 0.0265). A composite compliance index incorporating domains indicating adherence to diet, medications, and dialysis schedule identified other behavioral problems in poorly compliant patients. Hemodialysis patients characterized by this composite index as poorly compliant had shortened survival.     

The carbon footprints of home and in‐center maintenance hemodialysis in the United Kingdom

Climate change presents a global health threat. However, the provision of healthcare, including dialysis, is associated with greenhouse gas emissions. The aim of this study was to determine the carbon footprints of the differing modalities and treatment regimes used to deliver maintenance hemodialysis (HD), in order to inform carbon reduction strategies at the level of both individual treatments and HD programs. This was a component analysis study adhering to PAS2050. Emissions factors were applied to data that were collected for building energy use, travel and procurement. Thrice weekly in‐center HD has a carbon footprint of 3.8 ton CO₂ Eq per patient per year. The majority of emissions arise within the medical equipment (37%), energy use (21%), and patient travel (20%) sectors. The carbon footprint of providing home HD varies with the regime. For standard machines: 4 times weekly (4 days, 4.5 hours), 4.3 ton CO₂ Eq; 5 times weekly (5 days, 4 hours), 5.1 ton CO₂ Eq; short daily (6 days, 2 hours), 5.2 ton CO₂ Eq; nocturnal (3 nightly, 7 hours), 3.9 ton CO₂ Eq; and nocturnal (6 nightly, 7 hours), 7.2 ton CO₂ Eq. For NxStage equipment: short daily (5.5 days, 3 hours), 1.8 t CO₂ Eq; 6 nightly nocturnal (2.1 ton CO₂ Eq). The carbon footprint of HD is influenced more by the frequency of treatments than by their duration. The anticipated rise in the prevalence of home HD patients, dialyzing more frequently and for longer than in‐center patients, will increase the emissions associated with HD programs (despite reductions in patient travel emissions). Emerging technologies, such as NxStage, might offer a solution to this problem.     

Malnutrition‐inflammation‐coronary calcification in pediatric patients receiving chronic hemodialysis

Malnutrition, inflammation, and renal osteodystrophy parameters with resultant coronary calcification (CC) are associated with increased cardiovascular mortality in adults. Previous pediatric studies demonstrated CC in children but none assessed for an association between inflammation, malnutrition, renal osteodystrophy, and CC. To assess CC, ultrafast computerized tomogram was obtained for 16 pediatric patients (6 females; median age 17.2 years; range 9.1–21.2 years) receiving hemodialysis for ≥2 months. Inflammation was assessed by serum IL‐6, IL‐8, and C‐reactive protein levels on the day of the computerized tomogram scan; nutrition parameters included serum albumin, cholesterol, the body mass index standard deviation score, and normalized protein catabolic rate. Renal osteodystrophy parameters included time‐averaged serum calcium, phosphorus, total PTH, and calcitriol/calcium dose. Patients received hemodialysis thrice‐weekly; mean single pool Kt/V 1.48±0.13; and mean normalized protein catabolic rate 1.27±0.17 g/kg/day. Five of 16 patients had CC. Patients with CC were older (19.1±2.1 vs. 15.4±3.1 months; P=0.03), had longer dialysis vintage (49.4±15.3 vs. 17.2±10.5 months, P=0.0002), lower serum cholesterol (122±17.7 vs. 160.4±10.6 mg/dL, P=0.02), and higher phosphorus (9.05±1.2 vs. 6.1±0.96 mg/dL, P=0.0001). Mean serum albumin and normalized protein catabolic rate did not differ for patients with CC. All patients had elevated IL‐6 and IL‐8 levels compared with healthy norms; the mean IL‐6, IL‐8, and C‐reactive protein levels were not different in patients with CC. Coronary calcification was prevalent in older children receiving maintenance hemodialysis with a longer dialysis vintage. Worse renal osteodystrophy control and malnutrition (low cholesterol) may contribute to CC development.