Impact of incremental initiation of haemodialysis on mortality: a systematic review and meta-analysis.

BACKGROUND: Incremental haemodialysis initiation entails lower sessional duration and/or frequency than the standard 4 h thrice-weekly approach. Dialysis dose is increased as residual kidney function (RKF) declines. This systematic review evaluates its safety, efficacy and cost-effectiveness. METHODS: We searched MEDLINE, EMBASE, CINAHL and the Cochrane Library databases from inception to 27 February 2022. Eligible studies compared incremental haemodialysis (sessions either fewer than three times weekly or of duration <3.5 h) with standard treatment. The primary outcome was mortality. Secondary outcomes included treatment-emergent adverse events, loss of RKF, quality of life and cost effectiveness. The study protocol was prospectively registered. Risk of bias assessment used the Newcastle-Ottawa Scale and the revised Cochrane risk of bias tool, as appropriate. Meta-analyses were undertaken in Review Manager, Version 5.4. RESULTS: A total of 644 records were identified. Twenty-six met the inclusion criteria, including 22 cohort studies and two randomized controlled trials (RCTs). Sample size ranged from 48 to 50 596 participants (total 101 476). We found no mortality differences (hazard ratio = 0.99; 95% CI 0.80-1.24). Cohort studies suggested similar hospitalization rates though the two small RCTs suggested less hospitalization after incremental initiation (relative risk = 0.31; 95% CI 0.18-0.54). Data on other treatment-emergent adverse events and quality of life was limited. Observational studies suggested reduced loss of RKF in incremental haemodialysis. This was not supported by RCT data. Four studies reported reduced costs of incremental treatments. CONCLUSIONS: Incremental initiation of haemodialysis does not confer greater risk of mortality compared with standard treatment. Hospitalization may be reduced and costs are lower.

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.

Effect of Chronic Kidney Disease on Metabolic Rate: Studies Using Doubly Labelled Water.

OBJECTIVE: The causes of protein malnutrition and body composition changes in chronic kidney disease (CKD) are poorly understood. Alterations to metabolic rate caused by CKD may be a contributor. Using the doubly labeled water technique and indirect calorimetry, we set out to determine whether reduced glomerular filtration rate is associated with alterations to total energy expenditure (TEE) and resting energy expenditure (REE). We also aimed to determine whether TEE in patients with CKD can be easily predicted from a physical activity questionnaire. METHODS: In a prospective, observational study we evaluated 80 patients (52 men; mean age 56.7 ± 16.2 years) with CKD ranging from stage 1 to stage 5 with estimated glomerular filtration rate (eGFR) calculated by the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI). TEE was measured using doubly labeled water isotope excretion over 14 days (TEEDLW), REE by indirect calorimetry (REEIndirectCal) and physical activity level using the Stanford 7-day recall questionnaire. RESULTS: eGFR did not correlate with TEEDLW and REEIndirectCal. Findings with weight-adjusted energy measures were similar. REEIndirectCal and TEEDLW were significantly lower in patients whose eGFR was <50 mL/min/1.73 m2 and those with higher levels. There were similar findings with respect to weight-adjusted energy measures. In multivariable analysis, age, sex, and weight were independent predictors of TEEDLW and REEIndirectCal. eGFR did not predict TEE or REE in either of these models. CONCLUSION: There was no direct relationship between reduced renal function and metabolic rate. Differences in energy metabolism at lower levels of glomerular filtration rate are more likely to be due to factors such as age, body composition, and physical activity.

Beta-glucans in advanced CKD: role in endotoxaemia and inflammation.

BACKGROUND/AIMS: (1-3)-ß-D glucans (BG) are cellular components of yeasts and fungi. Elevated blood levels may be an adjunct in diagnosing invasive fungal infection, though can be high in dialysis patients without fungaemia. BG can also induce false positive signals in endotoxin detection assays (Limulus Amoebocyte Lysate [LAL] assay). We explored the relationship between BG levels, renal impairment, endotoxaemia and inflammation. METHODS: We measured serum BG levels, markers of inflammation and blood endotoxin levels in 20 controls, 20 with stages 1-3 chronic kidney disease (CKD), 20 with stages 4-5 CKD, 15 on peritoneal dialysis (PD) and 60 on haemodialysis (HD). Another 30 patients were studied before and after HD initiation. RESULTS: BG levels increased with advancing CKD, being highest in HD patients, 22% of whom had elevated levels (> 80 pg/ml). Levels increased significantly following HD initiation. Levels also correlated positively with CRP, TNFα, IL-6 levels, independently of CKD stage. Blood endotoxin was detectable by LAL assays in 10-53% of the CKD cohort, being most prevalent in the HD group, and correlating positively with BG levels. Adding BG blocking agent to the assay reduced endotoxin detection confining it to only 5% of HD patients. Levels of inflammatory markers were higher in those with detectable endotoxin - whether false- or true positives. CONCLUSION: BG levels increased with decreasing renal function, being highest in dialysis patients. High BG levels were associated with false positive blood endotoxin signals, and with markers of inflammation, independently of CKD stage. The cause for high BG levels is unknown but could reflect increased gut permeability and altered mononuclear phagocytic system function.

Initiating haemodialysis twice-weekly as part of an incremental programme may protect residual kidney function.

BACKGROUND: Initiating twice-weekly haemodialysis (2×HD) in patients who retain significant residual kidney function (RKF) may have benefits. We aimed to determine differences between patients initiated on twice- and thrice-weekly regimes, with respect to loss of kidney function, survival and other safety parameters. METHODS: We conducted a single-centre retrospective study of patients initiating dialysis with a residual urea clearance (KRU) of ≥3 mL/min, over a 20-year period. Patients who had 2×HD for ≥3 months during the 12 months following initiation of 2×HD were identified for comparison with those dialysed thrice-weekly (3×HD). RESULTS: The 2×HD group consisted of 154 patients, and the 3×HD group 411 patients. The 2×HD patients were younger (59 ± 15 versus 62 ± 15 years: P = 0.014) and weighed less (70 ± 16 versus 80 ± 18 kg: P < 0.001). More were females (34% versus 27%: P = 0.004). Fewer had diabetes (25% versus 34%: P = 0.04) and peripheral vascular disease (PVD) (13% versus 23%: P = 0.008). Baseline KRU was similar in both groups (5.3 ± 2.4 for 2 × HD versus 5.1 ± 2.8 mL/min for 3 × HD: P = 0.507). In a mixed effects model correcting for between-group differences in comorbidities and demographics, 3×HD was associated with increased rate of loss of KRU and separation of KRU. In separate mixed effects models, group (2×HD versus 3×HD) was not associated with differences in serum potassium or phosphate, and the groups did not differ with respect to total standard Kt/V. Survival, adjusted for age, gender, weight, baseline KRU and comorbidity (prevalence of diabetes, cardiac disease, PVD and malignancy) was greater in the 2×HD group (hazard ratio 0.755: P = 0.044). In sub-analyses, the survival benefit was confined to women, and those of less than median bodyweight. CONCLUSION: 2×HD initiation as part of an incremental programme with regular monthly monitoring of KRU was safe and associated with a reduced rate of loss of RKF early after dialysis initiation and improved survival. Randomized controlled trials of this approach are indicated.

Unexplained inflammation in end-stage kidney disease: Is the combination of enhanced gastrointestinal permeability and reticuloendothelial dysfunction its cause?

Unexplained chronic inflammation is prevalent in end-stage kidney disease, and contributes toward accelerated cardiovascular disease, and premature death. The source of inflammation is unclear, although increased gastrointestinal permeability is a likely contributory factor. Whether a "leaky" gut leads to penetration of the systemic circulation by gut-derived pathogens is at least partly dependent on Kupffer cell function. These resident liver macrophages are an important part of the reticuloendothelial system (RES), and there is evidence for Kupffer cell and reticuloendothelial dysfunction in chronic kidney disease. These observations are compatible with the inflammatory milieu of chronic kidney disease being of gut origin. Measuring gut permeability in chronic kidney disease is challenging. Use of fecal biomarkers and other novel serum biomarkers represent potential alternative tools. One such marker is (1-3)-Beta-D-glucan, a polysaccharide constituent of many fungal, bacterial, and plant cell walls; levels of (1-3)-Beta-D-glucan are elevated in hemodialysis patients. Gastrointestinal permeability and impaired removal by the RES may contribute to these high levels, suggesting potential importance as a biomarker. High levels of (1-3)-Beta-D-glucan also falsely elevate endotoxin measurements. Measuring the contribution of gastrointestinal permeability and RES dysfunction to systemic inflammation may be an important step in designing therapies to reduce systemic inflammation in chronic kidney disease.

Scaling Hemodialysis Target Dose to Reflect Body Surface Area, Metabolic Activity, and Protein Catabolic Rate: A Prospective, Cross-sectional Study.

BACKGROUND: Women and small men treated by hemodialysis (HD) have reduced survival. This may be due to use of total-body water (V) as the normalizing factor for dialysis dosing. In this study, we explored the equivalent dialysis dose that would be delivered using alternative scaling parameters matching the current recommended minimum Kt/V target of 1.2. STUDY DESIGN: Prospective cross-sectional study. SETTING & PARTICIPANTS: 1,500 HD patients on a thrice-weekly schedule, recruited across 5 different centers. PREDICTORS: Age, sex, weight, race/ethnicity, comorbid condition level, and employment status. OUTCOMES: Kt was estimated by multiplying V by 1.2. Kt/body surface area (BSA), Kt/resting energy expenditure (REE), Kt/total energy expenditure (TEE) and Kt/normalized protein catabolic rate (nPCR) equivalent to a target Kt/V of 1.2 were then estimated by dividing Kt by the respective parameters. MEASUREMENTS: Anthropometry, HD adequacy details, and BSA were obtained by standard procedures. REE was estimated using a novel validated equation. TEE was calculated from physical activity data obtained using the Recent Physical Activity Questionnaire. nPCR was estimated using a standard formula. RESULTS: Mean BSA was 1.87m2; mean REE, 1,545kcal/d; mean TEE, 1,841kcal/d; and mean nPCR, 1.03g/kg/d. For Kt/V of 1.2, there was a wide range of equivalent doses expressed as Kt/BSA, Kt/REE, Kt/TEE, and Kt/nPCR. The mean equivalent dose was lower in women for all 4 parameters (P<0.001). Small men would also receive lower doses compared with larger men. Younger patients, those with low comorbidity, those employed, and those of South Asian race/ethnicity would receive significantly lower dialysis doses with current practice. LIMITATIONS: Cross-sectional study; physical activity data collected by an activity questionnaire. CONCLUSIONS: Current dosing practices may risk underdialysis in women, men of smaller body size, and specific subgroups of patients. Using BSA-, REE-, or TEE-based dialysis prescription would result in higher dose delivery in these patients.

Measuring Residual Renal Function in Hemodialysis Patients without Urine Collection.

Many patients on hemodialysis retain significant residual renal function (RRF) but currently measurement of RRF in routine clinical practice can only be achieved using inter-dialytic urine collections to measure urea and creatinine clearances. Urine collections are difficult and inconvenient for patients and staff, and therefore RRF is not universally measured. Methods to assess RRF without reliance on urine collections are needed since RRF provides useful clinical and prognostic information and also permits the application of incremental hemodialysis techniques. Significant efforts have been made to explore the use of serum based biomarkers such as cystatin C, ß-trace protein and ß2 -microglobulin to estimate RRF. This article reviews blood-based biomarkers and novel methods using exogenous filtration markers which show potential in estimating RRF in hemodialysis patients without the need for urine collection.

The Effect of Intra-Dialytic Exercise on Inflammation and Blood Endotoxin Levels.

BACKGROUND: In healthy individuals, an acute inflammatory response occurs after intense exercise due to gut ischaemia and intestinal bacterial endotoxin translocation into the bloodstream. This process maybe exacerbated in patients who exercise during dialysis due to large volume shifts experienced by many during haemodialysis (HD). The acute effect of intra-dialytic exercise on blood endotoxins and inflammation is not known. METHOD: The effect of intra-dialytic exercise on blood endotoxin and inflammation was investigated in 10 patients and compared with resting haemodialysis. Blood was measured for endotoxin and inflammatory biomarkers before and after dialysis. RESULT: With the exception of one sample, all samples tested negative for endotoxin. Intra-dialytic exercise attenuated the rise of interleukin-6, tumour necrosis factor-α and high-sensitivity C-reactive protein after the HD procedure. CONCLUSION: Intra-dialytic exercise was not associated with an observable rise in blood endotoxin, although it may ameliorate the inflammatory effects of the HD procedure. Larger studies are needed to confirm this finding.

Predicting residual kidney function in hemodialysis patients using serum ß-trace protein and ß2-microglobulin.

Residual kidney function (RKF) contributes significant solute clearance in hemodialysis patients. Kidney Diseases Outcomes Quality Initiative (KDOQI) guidelines suggest that hemodialysis dose can be safely reduced in those with residual urea clearance (KRU) of 2 ml/min/1.73 m(2) or more. However, serial measurement of RKF is cumbersome and requires regular interdialytic urine collections. Simpler methods for assessing RKF are needed. ß-trace protein (ßTP) and ß2-microglobulin (ß2M) have been proposed as alternative markers of RKF. We derived predictive equations to estimate glomerular filtration rate (GFR) and KRU based on serum ßTP and ß2M from 191 hemodialysis patients based on standard measurements of KRU and GFR (mean of urea and creatinine clearances) using interdialytic urine collections. These modeled equations were tested in a separate validation cohort of 40 patients. A prediction equation for GFR that includes both ßTP and ß2M provided a better estimate than either alone and contained the terms 1/ßTP, 1/ß2M, 1/serum creatinine, and a factor for gender. The equation for KRU contained the terms 1/ßTP, 1/ß2M, and a factor for ethnicity. Mean bias between predicted and measured GFR was 0.63 ml/min and 0.50 ml/min for KRU. There was substantial agreement between predicted and measured KRU at a cut-off level of 2 ml/min/1.73 m(2). Thus, equations involving ßTP and ß2M provide reasonable estimates of RKF and could potentially be used to identify those with KRU of 2 ml/min/1.73 m(2) or more to follow the KDOQI incremental hemodialysis algorithm.

Incremental haemodialysis.

Thrice-weekly haemodialysis schedules have become the standard default haemodialysis prescription worldwide. Whereas the measurement of residual renal function is accepted practice for peritoneal dialysis patients and the importance of residual renal function in determining technique success is well established, few centres routinely assess residual renal function in haemodialysis patients. Although intradialytic hypotension and episodes of acute kidney injury may predispose to an earlier loss of residual renal function, a significant proportion of haemodialysis patients maintain some residual function long after dialysis initiation. As such, an incremental approach to the initiation of dialysis with careful monitoring of residual renal function may potentially provide some haemodialysis patients with an improved quality of life and greater preservation of residual renal function whilst fewer dialysis sessions may reduce health care costs. Prospective trials are required to determine the optimum approach to the initiation of haemodialysis for the oliguric patient. Once residual renal function has been lost, then dialysis prescriptions should be re-examined to consider the use of longer or more frequent treatment sessions and switching from low-flux to high-flux dialysis or haemodiafiltration to offset retention of middle sized molecules and protein-bound azotaemic solutes.

Endotoxemia in end-stage kidney disease.

Chronic unexplained inflammation remains a prevalent and clinically significant problem for patients with end-stage kidney disease (ESKD), especially in the dialysis population. The causes of persistent inflammation are likely to be multifactorial, but the underlying mechanisms remain to be elucidated. Endotoxins are reported to play a significant role in the pathogenesis of inflammation in patients with ESKD. However, blood endotoxin measurement with the Limulus amoebocyte lysate (LAL) assay is difficult with current detection systems. The reported degree and prevalence of endotoxemia varies in the literature. There are questions as to whether endotoxemia is truly present; whether the varied findings are due to methodological issues with the LAL assay and whether any endotoxemia that might be present plays a role in chronic inflammation frequently observed in ESKD patients. This review will discuss the challenges of accurate blood endotoxin detection, the potential source of blood endotoxins, and the significance of endotoxemia to patient with ESKD.

The role of natriuretic peptides in volume assessment and mortality prediction in Haemodialysis patients.

BACKGROUND: Maintaining optimal fluid balance is essential in haemodialysis (HD) patients but clinical evaluation remains problematic. Other technologies such as bioimpedance are emerging as valuable adjuncts. This study was undertaken to explore the potential utility of the natriuretic peptides - atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in the assessment of fluid status and cardiovascular risk in this setting. METHODS: This was a cross-sectional study carried out in an unselected cohort of 170 prevalent HD patients. Volume status was assessed by clinical parameters - the presence or absence of peripheral oedema, raised jugular venous pressure and basal lung crepitations; by extracellular fluid volume (ECFV) status determined by whole body bioimpedance; and by serum levels of BNP and ANP (pre- and post -dialysis). The relationships of ANP and BNP levels to clinical and bioimpedance parameters of volume status was determined. Patients were followed up for 5 years to assess the relationship of natriuretic peptide levels to mortality. RESULTS: Bioimpedance estimates of ECFV expansion (>105 % of ideal ECFV) was present in 52 % of patients pre-dialysis. A significant proportion (21 %) of pre-dialysis patients had a depleted ECFV (<95 % of ideal ECFV) pre-dialysis. The situation was reversed post-dialysis. A raised JVP >3 cm was the most reliable clinical sign of ECFV expansion inferred from bioimpedance measurements and natriuretic peptide levels. The vast majority of patients with this sign also had lung crepitations or peripheral oedema or both. BNP was a stronger predictor of ECFV expansion than either pre- or post-dialysis ANP. BNP was also a stronger predictor of five-year survival. CONCLUSION: Serum levels of BNP have a strong relationship to both volume status and survival in HD patients. We found no clear role for measurement of ANP, though changes in blood levels may be a sensitive indicator of acute changes in volume status. Whether monitoring levels of these peptides has a role in the management of volume status and cardiovascular risk requires further study.

A self-report comorbidity questionnaire for haemodialysis patients.

BACKGROUND: Patients with end-stage renal disease (ESRD) have multiple comorbid conditions. Obtaining comorbidity data from medical records is cumbersome. A self-report comorbidity questionnaire is a useful alternative. Our aim in this study was to examine the predictive value of a self-report comorbidity questionnaire in terms of survival in ESRD patients. METHODS: We studied a prospective cross-sectional cohort of 282 haemodialysis (HD) patients in a single centre. Participants were administered the self-report questionnaire during an HD session. Information on their comorbidities was subsequently obtained from an examination of the patient's medical records. Levels of agreement between parameters derived from the questionnaire, and from the medical records, were examined. Participants were followed-up for 18 months to collect survival data. The influence on survival of comorbidity scores derived from the self-report data (the Composite Self-report Comorbidity Score [CSCS]) and from medical records data--the Charlson Comorbidity Index [CCI] were compared. RESULTS: The level of agreement between the self-report items and those obtained from medical records was almost perfect with respect the presence of diabetes (Kappa score κ 0.97), substantial for heart disease and cancer (κ 0.62 and κ 0.72 respectively), moderate for liver disease (κ 0.51), only fair for lung disease, arthritis, cerebrovascular disease, and depression (κ 0.34, 0.35, 0.34 and 0.29 respectively). The CSCS was strongly predictive of survival in regression models (Nagelkerke R(2) value 0.202), with a predictive power similar to that of the CCI (Nagelkerke R(2) value 0.211). The influences of these two parameters were additive in the models--suggesting that these parameters make different contributions to the assessment of comorbidity. CONCLUSION: This self-report comorbidity questionnaire is a viable tool to collect comorbidity data and may have a role in the prediction of short-term survival in patients with end-stage renal disease on haemodialysis. Further work is required in this setting to refine the tool and define its role.

Disease-specific predictive formulas for energy expenditure in the dialysis population.

OBJECTIVE: Metabolic rate is poorly understood in advanced kidney disease because direct measurement is expensive and time-consuming. Predictive equations for resting energy expenditure (REE) are needed based on simple bedside parameters. Algorithms derived for normal individuals may not be valid in the renal population. We aimed to develop predictive equations for REE specifically for the dialysis population. DESIGN: Two-hundred subjects on maintenance dialysis underwent a comprehensive metabolic assessment including REE from indirect calorimetry. Parameters predicting REE were identified, and regression equations developed and validated in 20 separate subjects. RESULTS: Mean REE was 1,658 ± 317 kCal/day (males) and 1,380 ± 287 kCal/day (females). Weight and height correlated positively with REE (r(2) = 0.54 and 0.31) and negatively with age older than 65 years (r(2) = 0.18). The energy cost of a unitary kilogram of body weight increased nonlinearly for lower body mass index (BMI). Existing equations derived in normal individuals underestimated REE (bias 50-114 kCal/day for 3 equations). The novel derived equation was REE(kCal/day) = -2.497·Age·Factorage+0.011·height(2.023) + 83.573·Weight(0.6291) + 68.171·Factorsex, where Factorage = 1 if 65 years or older and 0 if younger than 65, and Factorsex = 1 if male and 0 if female. This algorithm performed at least as well as those developed for normals in terms of limits of agreement and reduced bias. In validation with the Bland-Altman technique, bias was not significant for our algorithm (-22 ± 96 kCal/day). The 95% limits of agreement were +380 to -424 kCal/day. CONCLUSION: Existing equations for REE derived from normal individuals are not valid in the dialysis population. The relatively increased REE in those with low BMI implies the need for higher dialysis doses in this subgroup. This disease-specific algorithm may be useful clinically and as a research tool to predict REE.

Impact of very low dose rivaroxaban in addition to dual antiplatelet therapy on endogenous fibrinolysis in acute coronary syndrome: The VaLiDate-R study.

BACKGROUND: Impaired endogenous fibrinolysis is adverse cardiovascular risk factor in acute coronary syndrome (ACS) patients. Addition of very low dose rivaroxaban (VLDR) to dual antiplatelet therapy (DAPT) reduces cardiovascular events but increases bleeding. OBJECTIVE: We aimed to assess whether addition of VLDR to DAPT can enhance endogenous fibrinolysis. METHODS: In a prospective, open-label trial, we assessed endogenous fibrinolysis in whole blood, in 549 patients with ACS using the Global Thrombosis Test (GTT) and Thromboelastography (TEG). Patients (n = 180) who demonstrated impaired endogenous fibrinolysis (lysis time [LT] >2000s with the GTT) were randomised 1:1:1 to (i) clopidogrel 75 mg daily; (ii) clopidogrel 75 mg daily plus rivaroxaban 2.5 mg twice daily; or (iii) ticagrelor 90 mg twice daily, for 30 days, in addition to aspirin. Fibrinolytic status was assessed at 0, 2, 4 and 8 weeks. The primary outcome was the change in LT from admission to week 4. We also measured thrombotic occlusion time (OT) at high shear, and rivaroxaban level. RESULTS: There was no difference between the groups with respect to LT or clot lysis with TEG, and no change in these parameters compared to baseline during study drug allocation. In the rivaroxaban plus clopidogrel group, OT was prolonged compared to the other groups, although rivaroxaban levels were low, suggesting non-compliance. CONCLUSION: Addition of rivaroxaban 2.5 mg twice daily to DAPT does not affect endogenous fibrinolysis of thrombus formed at either high or low shear. Further studies are needed to determine whether higher doses of rivaroxaban can favourably modulate fibrinolysis. CONDENSED ABSTRACT: Impaired endogenous fibrinolysis is a strong risk factor in ACS. We aimed to assess whether adding very low dose rivaroxaban (VLDR) to DAPT can enhance fibrinolysis. Fibrin and clot lysis were assessed in whole blood. ACS patients with impaired fibrinolysis were randomised 1:1:1 to clopidogrel 75 mg daily; clopidogrel 75 mg plus VLDR; or ticagrelor 90 mg twice daily, in addition to aspirin. At 30-days, there was no difference in lysis time between the groups, nor change from baseline. VLDR does not improve fibrinolysis at high or low shear. Further studies are needed to determine whether alternative antithrombotic regimens can enhance endogenous fibrinolysis.

Measures of treatment burden in dialysis: A scoping review.

BACKGROUND: Dialysis is a life-sustaining treatment for patients with advanced kidney failure, but it is extremely burdensome. Despite this, there are very few tools available to assess treatment burden within the dialysis population. OBJECTIVE: To conduct a scoping review of generic and disease-specific measures of treatment burden in chronic kidney disease, and assess their suitability for use within the dialysis population. DESIGN: We searched CINAHL, MEDLINE and the Cochrane Library for kidney disease-specific measures of treatment burden. Studies were initially included if they described the development, validation or use of a treatment burden measure or associated concept (e.g., measures of treatment satisfaction, quality of life, illness intrusiveness, disease burden etc.) in adult patients with chronic kidney disease. We also updated a previous scoping review exploring measures of treatment burden in chronic disease to identify generic treatment burden measures. RESULTS: One-hundred and two measures of treatment burden or associated concepts were identified. Four direct measures and two indirect measures of treatment burden were assessed, using adapted established criteria, for suitability for use within the dialysis population. The researchers outlined eight key dimensions of treatment burden: medication, financial, administrative, lifestyle, health care, time/travel, dialysis-specific factors, and health inequality. None of the measures adequately assessed all dimensions of treatment burden. CONCLUSION: Current measures of treatment burden in dialysis are inadequate to capture the spectrum of issues that matter to patients. There is a need for dialysis-specific burdens and health inequality to be assessed when exploring treatment burden to advance patient care.