Frank M. van der Sande

Acute Hemodynamic Response and Uremic Toxin Removal in Conventional and Extended Hemodialysis and Hemodiafiltration: A Randomized Crossover Study

BACKGROUNDnIntensive hemodialysis (HD) may have significant benefits. Recently, the role of extended hemodiafiltration (HDF) has gained interest. The aim of this study was to evaluate the acute effects of extended HD and HDF on hemodynamic response and solute removal.nnnSTUDY DESIGNnRandomized crossover trial.nnnSETTINGS & PARTICIPANTSnStable patients with end-stage renal disease undergoing conventional HD.nnnINTERVENTIONn13 patients randomly completed a single study of 4-hour HD (HD4), 4-hour HDF (HDF4), 8-hour HD (HD8), and 8-hour HDF (HDF8), with a 2-week interval between study sessions. Between study sessions, patients received routine conventional HD treatments.nnnOUTCOMESnAcute hemodynamic effects and uremic toxin clearance.nnnMEASUREMENTSnBlood pressure and heart rate, pulse wave analysis, cardiac output, and microvascular density by sublingual capillaroscopy, as well as relative blood volume and thermal variables, were measured. Clearance and removal of uremic toxins also were studied.nnnRESULTSnLong treatments showed more stability of peripheral systolic blood pressure (change during HD4, -21.7±15.6 mm Hg; during HDF4, -23.3±20.8 mm Hg; during HD8, -6.7±15.2 mm Hg [P=0.04 vs. HD4; P=0.08 vs. HDF4]; and during HDF8, -0.5±14.4 mm Hg [P=0.004 vs. HD4; P=0.008 vs. HDF4]). A similar observation was found for peripheral diastolic and central blood pressures. Cardiac output remained more stable in extended sessions (change during HD4, -1.4±1.5 L/min; during HDF4, -1.6±1.0 L/min; during HD8, -0.4±0.9 L/min [P=0.02 vs. HDF4]; and during HDF8, -0.5±0.8 L/min [P=0.06 vs. HD4; P=0.03 vs. HDF4), in line with the decreased relative blood volume slope in long dialysis. No differences in microvascular density were found. Energy transfer rates were comparable (HD4, 13.3±4.7 W; HDF4, 16.2±5.6 W; HD8, 14.2±6.0 W; and HDF8, 14.5±4.3 W). Small-molecule and phosphate removal were superior during long treatments. β2-Microglobulin and fibroblast growth factor 23 (FGF-23) reduction ratios were highest in HDF8.nnnLIMITATIONSnSmall sample size, only acute effects were studied.nnnCONCLUSIONSnTreatment time, and not modality, was the determinant for the hemodynamic response. HDF significantly improved removal of middle molecules, with superior results in extended HDF.

Insight Into Advance Care Planning for Patients on Dialysis

CONTEXTnAdvance care planning is not included in regular clinical care for patients on dialysis. Insight into life-sustaining treatment preferences and communication about end-of-life care is necessary to develop interventions to improve advance care planning for patients on dialysis.nnnOBJECTIVESnThis cross-sectional observational study aimed to understand the preferences for life-sustaining treatments of outpatients on dialysis and to study the quality of patient-physician communication about end-of-life care and barriers and facilitators to this communication.nnnMETHODSnThe following outcomes were assessed in 80 clinically stable dialysis patients: demographics, clinical characteristics, life-sustaining treatment preferences (cardiopulmonary resuscitation and mechanical ventilation, and Willingness to Accept Life-Sustaining Treatment instrument), preference for site of death, quality of communication (Quality of Communication Questionnaire), and barriers and facilitators to communication about end-of-life care (Barriers and Facilitators Questionnaire).nnnRESULTSnPatients were able to indicate their preferences for life-sustaining treatments and site of death. Preferences for life-sustaining treatments depend on the specific treatment, the expected outcome of treatment, and likelihood of an adverse outcome. Life-sustaining preferences were discussed with the nephrologist by 30.3% of the patients. Quality of the patient-physician communication about end-of-life care was rated poor. This study identified several barriers and facilitators to end-of-life care communication.nnnCONCLUSIONnPatients should receive information about treatment burden, expected outcome, and the likelihood of an adverse outcome when discussing life-sustaining treatments. Quality of patient-physician communication about end-of-life care needs to improve. Barriers and facilitators to communication about end-of-life care provide direction for future interventions to facilitate advance care planning for patients on dialysis.

Protein-bound uraemic toxins, dicarbonyl stress and advanced glycation end products in conventional and extended haemodialysis and haemodiafiltration

BACKGROUNDnProtein-bound uraemic toxins (PBUT), dicarbonyl stress and advanced glycation end products (AGEs) associate with cardiovascular disease in dialysis. Intensive haemodialysis (HD) may have significant clinical benefits. The aim of this study was to evaluate the acute effects of conventional and extended HD and haemodiafiltration (HDF) on reduction ratio (RR) and total solute removal (TSR) of PBUT, dicarbonyl stress compounds and AGEs.nnnMETHODSnThirteen stable conventional HD patients randomly completed a single study of 4-h HD (HD4), 4-h HDF (HDF4), 8-h HD (HD8) and 8-h HDF (HDF8) with a 2-week interval between the study sessions. RR and TSR of PBUT [indoxyl sulphate (IS), p-cresyl sulphate (PCS), p-cresyl glucuronide, 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid (CMPF), indole-3-acetic acid (IAA) and hippuric acid] of free and protein-bound AGEs [N(ε)-(carboxymethyl)lysine (CML), N(ε)-(carboxyethyl)lysine (CEL), Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine, pentosidine], as well as of dicarbonyl compounds [glyoxal, methylglyoxal, 3-deoxyglucosone], were determined.nnnRESULTSnCompared with HD4, HDF4 resulted in increased RR of total and/or free fractions of IAA and IS as well as increased RR of free CML and CEL. HD8 and HDF8 showed a further increase in TSR and RR of PBUT (except CMPF), as well as of dicarbonyl stress and free AGEs compared with HD4 and HDF4. Compared with HD8, HDF8 only significantly increased RR of total and free IAA and free PCS, as well as RR of free CEL.nnnCONCLUSIONSnDialysis time extension (HD8 and HDF8) optimized TSR and RR of PBUT, dicarbonyl stress and AGEs, whereas HDF8 was superior to HD8 for only a few compounds.

The first year on haemodialysis: a critical transition

The first year following the start of haemodialysis (HD) is associated with increased mortality, especially during the first 90–120 days after the start of dialysis. Whereas the start of dialysis has important effects on the internal environment of the patient, there are relatively few studies assessing changes in phenotype and underlying mechanisms during the transition period following pre-dialysis to dialysis care, although more insight into these parameters is of importance in unravelling the causes of this increased early mortality. In this review, changes in cardiovascular, nutritional and inflammatory parameters during the first year of HD, as well as changes in physical and functional performance are discussed. Treatment-related factors that might contribute to these changes include vascular access and pre-dialysis care, dialysate prescription and the insufficient correction of the internal environment by current dialysis techniques. Patient-related factors include the ongoing loss of residual renal function and the progression of comorbid disease. Identifying phenotypic changes and targeting risk patterns might improve outcome during the transition period. Given the scarcity of data on this subject, more research is needed.

An international feasibility study of home haemodialysis in older patients

BACKGROUNDnHome haemodialysis (HHD) is undergoing a significant revival. There is a global demographic shift with a rising mean age of dialysis patients. We postulated that intensive HHD may also benefit the older dialysis population. However, there is a lack of literature on the feasibility of HHD in older patients with end-stage renal disease (ESRD). The purpose of this study was to ascertain the feasibility of delivering HHD to older patients.nnnMETHODSnWe conducted a multi-centre multinational retrospective cohort study of HHD patients ≥65 years of age at the time of HHD initiation; 79 patients were included. Baseline demographic data included age at start of dialysis, race and sex. Dialysis characteristics including total weekly treatment hours, need for assistance, training time, dialysis access, modality and dialysis vintage were captured, as well as cause of ESRD and medical co-morbidities. The primary outcome was time to technique failure or death. Rates of hospitalization, cardiovascular events, non-infectious vascular access events and infections were collected.nnnRESULTSnMedian age at start was 68 (interquartile range 66-71) years. An arteriovenous fistula was the predominant access, and most patients were receiving <16 h of total weekly dialysis treatment. Family or nurse assistance for dialysis was required in 54% of patients. There were 17 (22%) deaths and 20 (26%) technique failures. The cumulative time at risk was 188 years. Event-free survival at 1, 2 and 5 years was 85, 77 and 24%, respectively, and technique survival was 92, 83 and 56%, respectively. Advancing age (categorized into quartiles) was an unadjusted risk factor for death and technique failure.nnnCONCLUSIONSnThis analysis confirms feasibility of HHD in patients 65 years or older at the start of this modality and should foster further research on the potential benefits of (intensive) HHD in older ESRD patients.

Association between intradialytic central venous oxygen saturation and ultrafiltration volume in chronic hemodialysis patients

Abstract Background Cardiac disease is highly prevalent in hemodialysis (HD) patients. Decreased tissue perfusion, including cardiac, due to high ultrafiltration volumes (UFVs) is considered to be one of the drivers of cardiac dysfunction. While central venous oxygen saturation (ScvO2) is frequently used as an indicator of cardiac output in non-uremic populations, the relationship of ScvO2 and UFV in HD patients remains unclear. Our aim was to determine how intradialytic ScvO2 changes associate with UFV. Methods We conducted a 6-month retrospective cohort study in maintenance HD patients with central venous catheters as vascular access. Intradialytic ScvO2 was measured with the Critline monitor. We computed treatment-level slopes of intradialytic ScvO2 over time (ScvO2 trend) and applied linear mixed effects models to assess the association between patient-level ScvO2 trends and UFV corrected for body weight (cUFV). Results We studied 6042 dialysis sessions in 232 patients. In about 62.4% of treatments, ScvO2 decreased. We observed in nearly 80% of patients an inverse relationship between cUFV and ScvO2 trend, indicating that higher cUFV is associated with steeper decline in ScvO2 during dialysis. Conclusions In most patients, higher cUFV volumes are associated with steeper intradialytic ScvO2 drops. We hypothesize that in a majority of patients the intradialytic cardiac function is fluid dependent, so that in the face of high ultrafiltration rates or volume, cardiac pre-load and consequently cardiac output decreases. Direct measurements of cardiac hemodynamics are warranted to further test this hypothesis.

Clinical parameters before and after the transition to dialysis

Introduction: The transition from pre‐dialysis chronic kidney disease (CKD) to post‐dialysis start is a critical period associated with high patient mortality and increased hospital admissions. Little is known about the trends of key clinical and laboratory parameters through this time of transition to start dialysis.

All-cause mortality in relation to changes in relative blood volume during hemodialysis

Abstract Background Relative blood volume (RBV) monitoring is widely used in hemodialysis (HD) patients, yet the association between intradialytic RBV and mortality is unknown. Methods Intradialytic RBV was recorded once/min during a 6-month baseline period; all-cause mortality was noted during follow-up. RBV at 1, 2 and 3u2009h into HD served as a predictor of all-cause mortality during follow-up. We employed Kaplan–Meier analysis, univariate and adjusted Cox proportional hazards models for survival analysis. Results We studied 842 patients. During follow-up (median 30.8u2009months), 249 patients (29.6%) died. The following hourly RBV ranges were associated with improved survival: first hour, 93–96% [hazard ratio (HR) 0.58 (95% confidence interval (CI) 0.42–0.79)]; second hour, 89–94% [HR 0.54 (95% CI 0.39–0.75)]; third hour, 86–92% [HR 0.46 (95% CI 0.33–0.65)]. In about one-third of patients the RBV was within these ranges and in two-thirds it was above. Subgroup analysis by median age (≤/> 61u2009years), sex, race (white/nonwhite), predialysis systolic blood pressure (SBP; ≤/> 130u2009mmHg) and median interdialytic weight gain (≤/> 2.3u2009kg) showed comparable favorable RBV ranges. Patients with a 3-h RBV between 86 and 92% were younger, had higher ultrafiltration volumes and rates, similar intradialytic average and nadir SBPs and hypotension rates, lower postdialysis SBP and a lower prevalence of congestive heart failure when compared with patients with an RBV >92%. In the multivariate Cox analysis, RBV ranges remained independent and significant outcome predictors. Conclusion Specific hourly intradialytic RBV ranges are associated with lower all-cause mortality in chronic HD patients.