Effect of Hemodiafiltration or Hemodialysis on Mortality in Kidney Failure.

BACKGROUND: Several studies have suggested that patients with kidney failure may benefit from high-dose hemodiafiltration as compared with standard hemodialysis. However, given the limitations of the various published studies, additional data are needed. METHODS: We conducted a pragmatic, multinational, randomized, controlled trial involving patients with kidney failure who had received high-flux hemodialysis for at least 3 months. All the patients were deemed to be candidates for a convection volume of at least 23 liters per session (as required for high-dose hemodiafiltration) and were able to complete patient-reported outcome assessments. The patients were assigned to receive high-dose hemodiafiltration or continuation of conventional high-flux hemodialysis. The primary outcome was death from any cause. Key secondary outcomes were cause-specific death, a composite of fatal or nonfatal cardiovascular events, kidney transplantation, and recurrent all-cause or infection-related hospitalizations. RESULTS: A total of 1360 patients underwent randomization: 683 to receive high-dose hemodiafiltration and 677 to receive high-flux hemodialysis. The median follow-up was 30 months (interquartile range, 27 to 38). The mean convection volume during the trial in the hemodiafiltration group was 25.3 liters per session. Death from any cause occurred in 118 patients (17.3%) in the hemodiafiltration group and in 148 patients (21.9%) in the hemodialysis group (hazard ratio, 0.77; 95% confidence interval, 0.65 to 0.93). CONCLUSIONS: In patients with kidney failure resulting in kidney-replacement therapy, the use of high-dose hemodiafiltration resulted in a lower risk of death from any cause than conventional high-flux hemodialysis. (Funded by the European Commission Research and Innovation; CONVINCE Dutch Trial Register number, NTR7138.).

Recommended calcium intake in adults and children with chronic kidney disease-a European consensus statement.

Mineral and bone disorders (MBD) are common in patients with chronic kidney disease (CKD), contributing to significant morbidity and mortality. For several decades, the first-line approach to controlling hyperparathyroidism in CKD was by exogenous calcium loading. Since the turn of the millennium, however, a growing awareness of vascular calcification risk has led to a paradigm shift in management and a move away from calcium-based phosphate binders. As a consequence, contemporary CKD patients may be at risk of a negative calcium balance, which, in turn, may compromise bone health, contributing to renal bone disease and increased fracture risk. A calcium intake below a certain threshold may be as problematic as a high intake, worsening the MBD syndrome of CKD, but is not addressed in current clinical practice guidelines. The CKD-MBD and European Renal Nutrition working groups of the European Renal Association (ERA), together with the CKD-MBD and Dialysis working groups of the European Society for Pediatric Nephrology (ESPN), developed key evidence points and clinical practice points on calcium management in children and adults with CKD across stages of disease. These were reviewed by a Delphi panel consisting of ERA and ESPN working groups members. The main clinical practice points include a suggested total calcium intake from diet and medications of 800-1000 mg/day and not exceeding 1500 mg/day to maintain a neutral calcium balance in adults with CKD. In children with CKD, total calcium intake should be kept within the age-appropriate normal range. These statements provide information and may assist in decision-making, but in the absence of high-level evidence must be carefully considered and adapted to individual patient needs.

Is increased subjective thirst associated with greater interdialytic weight gains, extracellular fluid and dietary sodium intake?

BACKGROUND: Some previous studies have reported an effect of increasing subjective thirst and interdialytic weight gains (IDWG), and that this may be influenced by nonadherence to dietary sodium restrictions, whereas others reported no such association. As such we wished to review the effect of self-reported thirst on IDWGs and dietary sodium intake. METHODS: Dialysis patients were asked to complete visual analogues thirst, distress thermometer (DT) scores and complete a sodium food frequency questionnaire (SFFQ). IDWG and pre and post dialysis volumes were measured with multifrequency bioelectrical impedance. RESULTS: One hundred and eleven patients completed the questionnaires and had bioimpedance measurements: 63% male, mean age 63.8 ± 16.1 years, 33% diabetic with a median thirst score 3 (0-5) and SFFQ 52.0 ± 18, and IDWG 2.1 ± 1.3%. Thirst was associated with DT (r = 0.28, p = 0.004) and negatively with age (r = -0.31, p < 0.001), but not SFFQ, IDWG, extracellular water, or dialysate sodium, or dialysate to plasma gradient. Patients with higher thirst scores were younger (58.0 ± 15.2 vs. 69.4 ± 15.0 years, p < 0.001) with higher DT scores (5 [2-7] vs. 2 [0-5], p < 0.001). On multivariate logistic analysis, only age was associated with self-reported thirst (odds ratio 0.95, 95% confidence limits 0.92-0.98, p < 0.001). CONCLUSION: We found that subjective thirst was greater for younger patients and those who reported higher levels of distress, but no association with IDWGs, dietary sodium intake, or dialysate sodium. However, most of our patients followed the dietary advice, as evidenced by the low SFFQ scores and % IDWGs. Whether thirst increases distress or distress increases subjective thirst remains to be determined.

Calcium mass balance in adults during single hemodialysis and hemodiafiltration treatments using lower calcium dialysate concentrations.

BACKGROUND: Debate continues as to the optimum hemodialysis (HD) dialysate calcium concentration. Although current guidelines advocate 1.25-1.5 mmol/L, some investigators have suggested these may cause calcium gains. As such we investigated whether using dialysate calcium of 1.25 mmol/L risked calcium gains, and whether there were differences between hemodiafiltration and high flux HD. METHODS: We continuously collect an aliquot of effluent dialysate during dialysis sessions, and calculated dialysis calcium mass balance by the difference between the amount of calcium delivered as fresh dialysate and that lost in effluent dialysate. RESULTS: We studied 106 stable outpatients, 64% male, mean age 64.4 ± 16.2 years, median dialysis vintage 32 (22-60) months. Most sessions (69%) used a 1.0 mmol/L calcium dialysate, with a median sessional loss of 13.7 (11.5-17.1) mmol, whereas using 1.25 mmol/L the median loss was 7.4 (4.9-10.1) mmol, but with 6.9% had a positive balance (p = 0.031 vs dialysate calcium 1.0 mmol/L). Most patients (85.8%) were treated by hemodiafiltration, but there was no difference in sessional losses (11.7 (8.4-15.8) vs 13.5 (8.1-16.8)) with high flux HD. Dialysis sessional calcium balance was associated with the use of lower dialysate calcium concentration (ß -19.5, 95% confidence limits (95%CL) -27.7 to -11.3, p < 0.001), and sessional duration (ß 0.07 (95% CL) 0.03-012, p = 0.002). CONCLUSION: Ideally, the choice of dialysate calcium should be individualized, but clinicians should be aware, that even when using a dialysate calcium of 1.25 mmol/L, some patients are at risk of a calcium gain during hemodiafiltration and high-flux hemodialysis.

Do patients dialysing with higher ultrafiltration rates report more intradialytic symptoms and longer postdialysis recovery times?

BACKGROUND: Many hemodialysis (HD) patients report intradialytic symptoms, and take time to recover postdialysis. To improve quality of life, patient groups have highlighted the need to reduce postdialysis fatigue and other peridialytic symptoms. As compartmental shifts of fluid during dialysis have been proposed to cause peridialytic symptoms we investigated whether patients dialysing with higher ultrafiltration rates (UFR) reported more intradialytic symptoms and recovery times. METHODS: We reviewed the hospital records of HD patients who completed a self-reported intradialytic symptom questionnaire, using a visual analogue scale, who had contemporaneous midweek pre- and postdialysis segmental bioimpedance measurements. RESULTS: Six hundred and five patients returned the peridialytic symptom questionnaire with pre- and postdialysis bioimpedance measurements. The majority were male (64.8%), mean age 64.2 ± 15.6 years, duration of dialysis treatment 26.8 (10.7-59.2) months, 85% treated by hemodiafiltration and mean dialysate temperature 35.4 ± 0.4°C. We divided patients into terciles according to UFR adjusted for weight, and there was a greater fall in the ratio of extracellular water (ECW) to total body water (TBW) postdialysis in the nonfistula arm from the lower to middle to higher tercile (0.8 (0-1.54) vs. 1.28 (0.52-1.85) vs. 1.54 (0.78-2.52)), trunk (1.5 (0.74-2.27) vs. 1.53 (0.99-2.2) vs. 1.98 (1.18-2.66)), left leg (1.56 (0.49-2.25) vs. 1.77 (1.24-2.43) vs. 2.08 (1.18-2.95)), lower versus higher tercile p < 0.05. However, no differences in intradialytic symptoms or postdialysis recovery times between the UFR terciles were observed. CONCLUSION: There were no differences in self-reported intradialytic symptoms or postdialysis recovery times with differing UFRs, despite changes in intracompartmental fluid shifts as measured by changes in ECW/TBW.

Bio-impedance spectroscopy added to a fluid management protocol does not improve preservation of residual kidney function in incident hemodialysis patients in a randomized controlled trial.

Avoiding excessive dialysis-associated volume depletion may help preserve residual kidney function (RKF). To establish whether knowledge of the estimated normally hydrated weight from bioimpedance measurements (BI-NHW) when setting the post-hemodialysis target weight (TW) might mitigate rate of loss of RKF, we undertook an open label, randomized controlled trial in incident patients receiving HD, with clinicians and patients blinded to bioimpedance readings in controls. A total of 439 patients with over 500 ml urine/day or residual GFR exceeding 3 ml/min/1.73m2 were recruited from 34 United Kingdom centers and randomized 1:1, stratified by center. Fluid assessments were made for up to 24 months using a standardized proforma in both groups, supplemented by availability of BI-NHW in the intervention group. Primary outcome was time to anuria, analyzed using competing-risk survival models adjusted for baseline characteristics, by intention to treat. Secondary outcomes included rate of RKF decline (mean urea and creatinine clearance), blood pressure and patient-reported outcomes. There were no group differences in cause-specific hazard rates of anuria (0.751; 95% confidence interval (0.459, 1.229)) or sub-distribution hazard rates (0.742 (0.453, 1.215)). RKF decline was markedly slower than anticipated, pooled linear rates in year 1: -0.178 (-0.196, -0.159)), year 2: -0.061 (-0.086, -0.036)) ml/min/1.73m2/month. Blood pressure and patient-reported outcomes did not differ by group. The mean difference agreement between TW and BI-NHW was similar for both groups, Bioimpedance: -0.04 kg; Control: -0.25 kg. Thus, use of a standardized clinical protocol for fluid assessment when setting TW is associated with excellent preservation of RKF. Hence, bioimpedance measurements are not necessary to achieve this.

Randomized, controlled clinical trial of the DIALIVE liver dialysis device versus standard of care in patients with acute-on- chronic liver failure.

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is characterized by severe systemic inflammation, multi-organ failure and high mortality rates. Its treatment is an urgent unmet need. DIALIVE is a novel liver dialysis device that aims to exchange dysfunctional albumin and remove damage- and pathogen-associated molecular patterns. This first-in-man randomized-controlled trial was performed with the primary aim of assessing the safety of DIALIVE in patients with ACLF, with secondary aims of evaluating its clinical effects, device performance and effect on pathophysiologically relevant biomarkers. METHODS: Thirty-two patients with alcohol-related ACLF were included. Patients were treated with DIALIVE for up to 5 days and end points were assessed at Day 10. Safety was assessed in all patients (n = 32). The secondary aims were assessed in a pre-specified subgroup that had at least three treatment sessions with DIALIVE (n = 30). RESULTS: There were no significant differences in 28-day mortality or occurrence of serious adverse events between the groups. Significant reduction in the severity of endotoxemia and improvement in albumin function was observed in the DIALIVE group, which translated into a significant reduction in the CLIF-C (Chronic Liver Failure consortium) organ failure (p = 0.018) and CLIF-C ACLF scores (p = 0.042) at Day 10. Time to resolution of ACLF was significantly faster in DIALIVE group (p = 0.036). Biomarkers of systemic inflammation such as IL-8 (p = 0.006), cell death [cytokeratin-18: M30 (p = 0.005) and M65 (p = 0.029)], endothelial function [asymmetric dimethylarginine (p = 0.002)] and, ligands for Toll-like receptor 4 (p = 0.030) and inflammasome (p = 0.002) improved significantly in the DIALIVE group. CONCLUSIONS: These data indicate that DIALIVE appears to be safe and impacts positively on prognostic scores and pathophysiologically relevant biomarkers in patients with ACLF. Larger, adequately powered studies are warranted to further confirm its safety and efficacy. IMPACT AND IMPLICATIONS: This is the first-in-man clinical trial which tested DIALIVE, a novel liver dialysis device for the treatment of cirrhosis and acute-on-chronic liver failure, a condition associated with severe inflammation, organ failures and a high risk of death. The study met the primary endpoint, confirming the safety of the DIALIVE system. Additionally, DIALIVE reduced inflammation and improved clinical parameters. However, it did not reduce mortality in this small study and further larger clinical trials are required to re-confirm its safety and to evaluate efficacy. CLINICAL TRIAL NUMBER: NCT03065699.

Navigating through the haemostatic paradox in kidney failure: A practical overview.

Chronic kidney disease (CKD) affects around 9.1% of humankind globally resulting in a significant health burden. Some of these individuals will also require renal replacement therapy with dialysis due to complete kidney failure. Patients with CKD are known to be at increased risk of both bleeding and thrombosis. Often it is very difficult to manage these yin and yang since both risks tend to co-exist. Clinically, very few studies have looked at the effects of antiplatelet agents and anticoagulants in this highly vulnerable subgroup of medical patients and evidence is very limited. This review attempts to explain the current state-of-the-art regarding the basic science of haemostasis in patients with end-stage kidney disease. We also try to transfer this knowledge into the clinics by looking at some common haemostasis challenges that are encountered in this cohort of patients and what evidence and guidance there is for their optimal management.

Long-term peridialytic blood pressure changes are related to mortality.

BACKGROUND: In chronic haemodialysis (HD) patients, the relationship between long-term peridialytic blood pressure (BP) changes and mortality has not been investigated. METHODS: To evaluate whether long-term changes in peridialytic BP are related to mortality and whether treatment with HD or haemodiafiltration (HDF) differs in this respect, the combined individual participant data of three randomized controlled trials comparing HD with HDF were used. Time-varying Cox regression and joint models were applied. RESULTS: During a median follow-up of 2.94 years, 609 of 2011 patients died. As for pre-dialytic systolic BP (pre-SBP), a severe decline (≥21 mmHg) in the preceding 6 months was independently related to increased mortality [hazard ratio (HR) 1.61, P = .01] when compared with a moderate increase. Likewise, a severe decline in post-dialytic diastolic BP (DBP) was associated with increased mortality (adjusted HR 1.96, P < .0005). In contrast, joint models showed that every 5-mmHg increase in pre-SBP and post-DBP during total follow-up was related to reduced mortality (adjusted HR 0.97, P = .01 and 0.94, P = .03, respectively). No interaction was observed between BP changes and treatment modality. CONCLUSION: Severe declines in pre-SBP and post-DBP in the preceding 6 months were independently related to mortality. Therefore peridialytic BP values should be interpreted in the context of their changes and not solely as an absolute value.

The changing face of dialyzer membranes and dialyzers.

The key goals for dialysis treatments are to prevent the progressive accumulation of waste products of metabolism and volume overload. Traditionally uremic solutes have been classified according to molecular weight and termed small, middle sized, and large solutes. Solute clearance during dialysis sessions will potentially be by diffusion, convection and adsorption. Dialyzer membranes act as a semi-permeable membrane restricting solute removal predominantly by size. Small molecules move faster than large molecules, so small solutes are readily removed by diffusion. Increasing the size of the pores in the membrane will potentially allow middle and larger sized solutes to pass through the dialyzer membrane, although in practice there is a limit to increasing pore sizes to prevent the loss of albumin and other important proteins. Differences in membrane surface and charge will influence protein absorption. The removal of fluid during dialysis depends in part on the hydraulic permeability of the membrane. Combining higher hydraulic permeability and larger sized pores increases convective clearance with solutes moving across the membrane with the water movement. Depending upon dialyzer design, higher hydrostatic pressure as blood enters the dialyzer leads to a variable amount of internal diafiltration, so improving the clearance of middle sized solutes. Although the dialyzer membrane plays a key role in solute clearance, the design of the casing and header also play a role in directing the countercurrent blood and dialysate flows to maximize the surface area available for diffusive and convective clearances.

The effect of changing dialysate bicarbonate concentration on serum bicarbonate, body weight and normalized nitrogen appearance rate.

INTRODUCTION: Most hemodialysis machines deliver a fixed bicarbonate concentration. Higher concentrations may improve acidosis, but risk post-hemodialysis alkalosis, whereas lower concentrations potentially increase acidosis but reduce alkalosis. We reviewed the effects of lowering dialysate bicarbonate. METHODS: We reviewed peri-dialysis chemistries in patients switching to a lower bicarbonate dialysate at 4 time points over 19 months. RESULTS: We studied 126 patients, mean age 63.7 ± 16.3 years, 57.9% males. Post-hemodialysis alkalosis fell from 1.6 to 0.3% sessions, but pre-hemodialysis acidosis increased from 11.9 to 23.8% sessions (p = 0.005) reducing dialysate bicarbonate from 32 to 28 mmol/L. After 3 months, pre-hemodialysis serum bicarbonate fell (21.1 ± 2.3 to 19.8 ± 2.2 mmol/L), and post-hemodialysis (24.9 ± 2.1 to 22.5 ± 2.0 mmol/L, p < 0.001) with a fall in pre-hemodialysis weight from 74.6 ± 20.7 to 71.7 ± 18.2 kg, normalized protein nitrogen accumulation rate 0.8 ± 0.28 to 0.77 ± 0.2 g/kg/day, p < 0.05, and serum albumin 39.7 ± 4.2 to 37.7 ± 4.9 g/L, p < 0.001. Thereafter, apart from pre- and post-hemodialysis serum bicarbonate, weight and normalized protein nitrogen accumulation stabilized, although albumin remained lower (37.6 ± 4.0 g/L, p < 0.001). On multivariate logistic analysis, serum bicarbonate increased more with lower pre-hemodialysis bicarbonate standardized coefficient ß 0.5 (95% confidence interval -0.6 to -0.42), increased normalized protein nitrogen accumulation ß 0.2 (0.96 to 2.38), p < 0.001, and session time ß 0.09, (0.47 to 5.98), p < 0.022, and less with lower dialysate bicarbonate 0.0-0.23 (-1.54 to -0.74), p < 0.001. CONCLUSION: Increases in SE-Bic with hemodialysis, depend on the bicarbonate gradient, session time and nPNA. Lower D-Bic reduces post-hemodialysis alkalosis but increases pre-hemodialysis acidosis and may initially have adverse effects on weight and normalized protein nitrogen accumulation.

The changing pattern of COVID-19 infection in hemodialysis and peritoneal dialysis patients.

INTRODUCTION: Following the first wave of COVID-19 there have been several variants. We wished to review the number and severity of infections with the different variants in a population of hemodialysis (HD) and peritoneal dialysis (PD) patients. METHODS: We reviewed the outcomes and results in HD and PD patients testing positive for COVID-19 between March 2020 and August 2022. RESULTS: Seven hundred and ninety-five cases of COVID-19 were recorded in 710 dialysis patients. More HD patients than PD contracted wild type (21.4% vs. 6.8%), delta (23.3% vs 6.3%), and omicron (27.7% vs. 14.7%), all p < 0.01, but no difference with alpha (4.6% vs. 6.3%) or beta variants (5.7% vs. 6.85%). Hospitalization and death were greatest for alpha followed by wild type, beta, delta, and omicron (60.6% vs. 57% vs. 47.5% vs. 21.2% vs. 19.3%), respectively, p < 0.001. C reactive protein progressively increased from outpatient management to hospitalization to hospitalization with critical care or death (14 (4-30) vs. 41 (18-101) vs. 94 (47-168) mg/L, p < 0.001. Despite previous infection and vaccination 85 (12%) patients had two or more infections with COVID-19. CONCLUSION: Disease severity declined and survival improved as the virus mutated from wild-type and alpha to beta, delta, and omicron variants. Whether this related to reduction in viral virulence, vaccination, natural acquired immunity, or introduction of pharmacological treatments remains to be determined. Government lockdowns and enhanced infection control measures reduced the percentage of HD patients contracting alpha and beta variants to that of PD. Vaccination and prior infection did not prevent reinfection.

Weight loss and weight gains in patients starting peritoneal dialysis; the effect of peritonitis.

AIM: Earlier studies reported that peritoneal dialysis (PD) patients gained fat mass after initiating dialysis. Clinical practice and demographics have changed over time with earlier initiation of dialysis and increasing numbers of elderly, co-morbid patients. As such, we wished to review changes in body composition with dialysis. METHODS: Changes in body composition were compared by dual x-ray absorptiometry (DXA) in 151 adult PD patients, 81 males (54.6%), 50 diabetic (30.1%), mean age 60.5 ± 16.7 years, shortly after starting PD and then a median of 24 months later, to allow for the initial impact of dialysis. RESULTS: Overall, weight appeared stable (71.7 ± 15.4 vs. 71.9 ± 15.3 kg). On follow-up, total weekly urea clearance fell from 2.29 (1.85-3.0) to 1.93 (1.63-2.4) whereas peritoneal glucose absorption increased from 119 (46-217) to 321 (187-805) mmol/day, p < .001, and estimated dietary protein (nPNA) fell from 0.92 ± 0.23 to 0.86 ± 0.23 g/kg/day, p = .006. However, 69 (45.7%) patients gained weight, with greater change in both lean and fat mass index versus those with weight loss (0.8 [-0.5 to 2.0] vs. -0.7 [-2.1 to 0.2] and 0.9 [-0.1 to 2.3] vs. 0 [-2.6 to 0.8] kg/m2 , p < .001), respectively. Although there were no differences in hospital admissions, patients who gained weight experienced fewer episodes of PD peritonitis (0 [0-1] vs. 1[0-2], p = .019). CONCLUSION: Dietary protein intake declined over time, and more PD patients lost weight. The major difference between those who gained and lost weight was episodes of peritonitis. Greater attention to nutritional support may potentially reduce loss of lean body mass.

Segmental bioimpedance in pregnant end stage renal failure patient for dry weight titration and volume management (case report).

BACKGROUND: Volume assessment, dry weight titration, and blood pressure control in pregnant kidney failure patients are often challenging, with physiological fluid accumulation in the trunk and lower limbs and an increased risk of preeclampsia. We used segmental bioimpedance in the volume management of our kidney failure patient on haemodialysis. CASE PRESENTATION: We report a case of a female patient on maintenance haemodiafiltration with no residual kidney function for whom we used segmental bioimpedance to guide dry weight adjustment. At different gestational periods, we targeted a different extracellular to total body water ratio according to body segments. This allowed us to support her high-risk pregnancy, identify her as probably developing preeclampsia and trigger a plan for closer monitoring and delivery during the third trimester when she had rapid weight gain. CONCLUSION: Segmental bioimpedance is a practical, simple, and non-invasive test that can be performed at the dialysis unit and is useful as an adjunct decision-making tool in the management of pregnant dialysis patients.

A multicenter feasibility randomized controlled trial to assess the impact of incremental versus conventional initiation of hemodialysis on residual kidney function.

Twice-weekly hemodialysis, as part of incremental initiation, has reported benefits including preservation of residual kidney function (RKF). To explore this, we initiated a randomized controlled feasibility trial examining 55 incident hemodialysis patients with urea clearance of 3 ml/min/1.73 m2 or more across four centers in the United Kingdom randomized to standard or incremental schedules for 12 months. Incremental hemodialysis involved twice-weekly sessions, upwardly adjusting hemodialysis dose as RKF was lost, maintaining total (Dialysis+Renal) Std Kt/V above 2. Standard hemodialysis was thrice weekly for 3.5-4 hours, minimum Dialysis Std Kt/V of 2. Primary outcomes were feasibility parameters and effect size of group differences in rate of loss of RKF at six months. Health care cost impact and patient-reported outcomes were explored. Around one-third of patients met eligibility criteria. Half agreed to randomization; 26 received standard hemodialysis and 29 incremental. At 12 months, 21 incremental patients remained in the study vs 12 in the standard arm with no group differences in the urea clearance slope. Ninety-two percent of incremental and 75% of standard arm patients had a urea clearance of 2 ml/min/1.73 m2 or more at six months. Serious adverse events were less frequent in incremental patients (Incidence Rate Ratio 0.47, confidence interval 0.27-0.81). Serum bicarbonate was significantly lower in incremental patients indicating supplementation may be required. There were three deaths in each arm. Blood pressure, extracellular fluid and patient-reported outcomes were similar. There was no signal of benefit of incremental hemodialysis in terms of protection of RKF or Quality of Life score. Median incremental hemodialysis costs were significantly lower compared to standard hemodialysis. Thus, incremental hemodialysis appears safe and cost-saving in incident patients with adequate RKF, justifying a definitive trial.

Patient Preferences for Longer or More Frequent In-Center Hemodialysis Regimens: A Multicenter Discrete Choice Study.

RATIONALE & OBJECTIVE: Longer and more frequent hemodialysis sessions are associated with both benefits and harms. However, their relative importance to patients and how they influence acceptability for patients have not been quantified. STUDY DESIGN: Discrete-choice experiment in which a scenario followed by 12 treatment choice sets were presented to patients in conjunction with varying information about the clinical impact of the treatments offered. SETTING & PARTICIPANTS: Patients with kidney failure treated with maintenance dialysis for≥1 year in 5 UK kidney centers. PREDICTORS: Length and frequency of hemodialysis sessions and their prior reported associations with survival, quality of life, need for fluid restriction, hospitalization, and vascular access complications. OUTCOME: Selection of longer (4.5 hours) or more frequent (4 sessions per week) hemodialysis regimens versus remaining on 3 sessions per week with session lengths of 4 hours. ANALYTICAL APPROACH: Multinomial mixed effects logistic regression estimating the relative influence of different levels of the predictors on the selection of longer and more frequent dialysis, controlling for patient demographic characteristics. RESULTS: Among 183 prevalent in-center hemodialysis patients (mean age of 63.7 years, mean dialysis vintage of 4.7 years), 38.3% (70 of 183) always chose to remain on regimens of 3 sessions per week with session duration of 4 hours. Depicted associations of increasing survival and quality of life, reduced need for fluid restriction, and avoiding additional access complications were all significantly associated with choosing longer or more frequent treatment regimens. Younger age, fatigue, previous experience of vascular access complications, absence of heart failure, and shorter travel time to dialysis centers were associated with preference for 4 sessions per week. Patients expressed willingness to trade up to 2 years of life to avoid regimens of 4 sessions per week or access complications. After applying estimated treatment benefits and harms from existing literature, the fully adjusted model revealed that 27.1% would choose longer regimens delivered 3 times per week and 34.3% would choose 4 hours 4 times per week. Analogous estimates for younger fatigued patients living near their unit were 23.5% and 62.5%, respectively. LIMITATIONS: Estimates were based on stated preferences rather than observed behaviors. Predicted acceptance of regimens was derived from data on treatment benefits and harms largely sourced from observational studies. CONCLUSIONS: Predicted acceptance of longer and more frequent hemodialysis regimens substantially exceeds their use in current clinical practice. These findings underscore the need for robust data on clinical effectiveness of these more intensive regimens and more extensive consideration of patient choice in the selection of dialysis regimens.

Energy expenditure estimates in chronic kidney disease using a novel physical activity questionnaire.

BACKGROUND: Physical activity (PA) levels are low in patients with advanced chronic kidney disease (CKD), and associate with increased morbidity and mortality. Reliable tools to assess PA in CKD are scarce. We aimed to develop and validate a novel PA questionnaire for use in CKD (CKD-PAQ). METHODS: In Phase 1, a prototype questionnaire was developed based on the validated recent PAQ (RPAQ). Structured feedback on item relevance and clarity was obtained from 40 CKD patients. In Phase 2, the questionnaire was refined in three iterations in a total of 226 CKD patients against 7-day accelerometer and RPAQ measurements. In Phase 3, the definitive CKD-PAQ was compared with RPAQ in 523 CKD patients. RESULTS: In the final iteration of Phase 2, CKD-PAQ data were compared with accelerometer-derived and RPAQ data in 60 patients. Mean daily metabolic equivalent of task (MET) and total energy expenditure (TEE) levels were similar by all methods. Intraclass correlation coefficients showed fair (MET) and good (TEE) agreement between accelerometry and both CKD-PAQ and RPAQ. Agreement between questionnaires was excellent. The mean [standard deviation (SD)] daily MET bias was 0.035 (0.312) for CKD-PAQ and 0.018 (0.326) for RPAQ. The mean (SD) TEE bias was 91 (518) for CKD-PAQ and 44 (548) kcal for RPAQ. Limits of agreement (LOA) were wide for both parameters, with less dispersion of CKD-PAQ values. In Phase 3, agreement between questionnaires was good (MET) and excellent (TEE). Bias of CKD-PAQ-derived mean (SD) daily MET from RPAQ-derived values was 0.031 (0.193), with 95% LOA -0.346 to 0.409. Corresponding mean (SD) values for TEE were 48 (325) and -588 to 685 kcal/day. CKD-PAQ appeared to improve discrimination between low activity groups. CONCLUSIONS: CKD-PAQ performs comparably to the RPAQ though it is shorter, easier to complete, and may better capture low-level activity and improve discrimination between low activity groups.

The rationale and clinical potential of on-line hemodiafiltration as renal replacement therapy.

On-line hemodiafiltration (ol-HDF) was developed in the 1980s in response to the unmet medical needs observed with conventional low- and high-flux hemodialysis. Firstly, the limited overall efficacy of conventional HD treatment programs as compared to native kidney function has been consistently documented over the broad MW spectrum of uremic toxins as well as fluid volume and hemodynamic control. Secondly, the unphysiological profile of intermittent treatment leading to repetitive dialysis-induced hemodynamic stress is now a well-recognized component of cardiovascular disease and end organ damage. Thirdly, the bioincompatibility of patient-dialysis system leading to dialysis-induced biological reactions also identified as contributing to dialytic morbidity and mortality. To overcome these limitations and pitfalls, alternative convective-based therapies (hemofiltration and hemodiafiltration), using higher hemoincompatible membranes and ultrapure dialysis fluid, were proposed as a solution to enhance and enlarge MW spectrum of uremic compounds cleared and to reduce dialysis-patient biological interactions. In this context, online HDF appeared soon as the best viable and efficient renal replacement modality to cover these needs. Clinical development and implementation of ol-HDF showed also that dialytic convective dose matters with a threshold point (23 L/1.73 m2 in postdilution mode) to observe clinical benefits and outcomes improvements.

Prescription of online hemodiafiltration (ol-HDF).

HDF prescription should be able to satisfy the delivery of an optimal dialytic convective dose. Several factors are implicated in this endeavor. High blood flow rate is crucial to warranty processing an adequate blood volume and to ensure the highest shear rate per fiber needed to cleanse and prevent membrane fouling. A highly permeable dialyzer is needed with a surface area aligned to blood flow and performance needs. Anticoagulation requires specific adaptation in case of low molecular weight heparin use. By default, HDF prescription modality should ideally start by postdilution mode with a stepwise increment of convective dose by probing patient tolerance and efficacy. Alternative substitution modality should be considered if dialytic convective dose could not be achieved in the usual time frame. Convective dose prescription relies either on a manual mode (pressure control or volume control) or on automated mode (ultrafiltration control) depending on the technical options of the HDF machines. Dialysate flow rate is regulated by the HDF machine but should preferably keep constant dialysis fluid flowing the dialyzer with a Qb:Qd ratio of 1.4. Treatment time should not be reduced with HDF prescription. Treatment time should fit with patient tolerance (hemodynamic, osmotic, and solute shifts) and overall solute removal efficiency. Electrolytic prescription does not require specific adjustments as compared with conventional dialysis, but the patient needs to be monitored regularly and dialysate electrolyte adjusted to lab tests. A stepwise approach for implementing ol-HDF is preferable depending on the initial condition of the patient. Three particular cases may be considered: late-stage chronic kidney disease patient transitioning to renal replacement therapy, stable dialysis patient switching to HDF, and unstable or fragile patient or specific treatment schedule. Optimal dosing of HDF and personalized care to ensure treatment adequacy is the main goal for renal replacement therapy to improve patient outcomes. That should be ensured with HDF treatment.

On-line hemodiafiltration therapy for end-stage kidney disease patients: Promises for the future? What's next?

On-line hemodiafiltration (OL-HDF) is currently the most advanced form of blood purification modality leading convective-based therapies in end-stage kidney disease patients. By adding a high convective component to the diffusive clearance achieved with highly permeable dialyzers, OL-HDF reinforces removal of small MWt compounds and enlarges the spectrum of uremic compounds cleared up to middle and large MWt compounds. The biological and clinical benefits of convective-based therapy are currently also being explored in a revisited hybrid modality, combining an increased internal filtration process with a more open membrane. Regular use of ultrapure dialysis fluid required by convective-based therapies improves the bio-incompatibility of the extracorporeal circuit so reducing inflammatory responses. On-line production of substitution fluid, relying on a cold sterilization by ultrafiltration, has several advantages: First, it is a safe and established process; and second, it provides an unlimited amount of substitution fluid at the same cost as regular ultrapure dialysis fluid. As such, OL-HDF is adaptable to all substitution modalities (post, pre, or mixed-HDF), thus allowing the dialytic convective dose to be adjusted to the individual patient needs. The development of OL-HDF opens new pathways such as task automation simplifying care workflow. All these features make OL-HDF the most versatile dialysis modality that can be now integrated in various treatment schedules according to session time and frequency (daily, nocturnal, or alternate day) or location (incenter, satellite, or potentially home-based therapy).