Energy Expenditure in Kidney Failure: Implications for Management

Renal replacement therapy, in the form of dialysis or transplantation, is the cornerstone of management for end-stage renal disease. UK renal registry shows nearly half of those needing renal replacement therapy are treated by dialysis – predominantly by haemodialysis. Patients on renal replacement therapy have increased mortality risk compared to age matched general population. Moreover, some specific subgroups of patients on haemodialysis have increased risk of mortality than expected. The survival benefit seen in women in the general population is attenuated resulting in similar survival for men and women on haemodialysis therapy. In addition, obese individuals and those of non-Caucasian origin have better survival outcome. Though the underlying reason for these findings is not clear and is likely to be multi-factorial, it has been hypothesised that this paradox could be due to the current practice of normalising dialysis dose to total body water. A number of metabolic factors – body surface area, resting energy expenditure and total energy expenditure – have been proposed as alternative to total body water for scaling dialysis dose. There were two overarching aims of this work – one was to study the effect of declining renal function on resting and total energy expenditure and to study the influence of various energy expenditure measures on uraemic toxin generation. The second was to study the impact on survival outcome of using these alternate parameters for normalising dialysis dose and to derive dialysis dose adjustments based on these metabolic parameters. In order to study these aims, studies were designed to explore different aspects of energy expenditure measures along with a longitudinal study to examine the impact of these parameters on survival outcome. The relationship between energy metabolism, body composition and uraemic toxin generation was studied with a retrospective analysis of 166 haemodialysis patients in whom urea generation rate was used as surrogate marker of uraemic toxin generation. It was found that total energy expenditure and fat-free mass predicted uraemic toxin generation after adjustment for other relevant variables. This study provided the preliminary data which was useful in designing further studies for this work. The effect of renal function on resting and total energy expenditure was studied in 80 patients with varying stages of chronic kidney disease who were not on renal replacement therapy. Resting and total energy expenditures were measured directly using gold-standard methods. It was found that declining renal function did not have a significant influence on either of these measures. This supports the hypothesis that metabolic rate is the driving force for glomerular filtration rate and not vice-versa. The directly measured energy expenditure measures were also found to have a moderately strong relationship with urea generation rate in these patients not on renal replacement therapy. The impact of physical activity on uraemic toxin generation, and thereby dialysis requirement, was studied in a prospective cross-sectional study of 120 haemodialysis patients in whom the physical activity was measured by an accelerometer device. Results from the study showed physical activity level to be a significant predictor of uraemic toxin generation after adjustment for gender and body size differences. This study results stressed the importance of adjusting dialysis dose based on individual’s physical activity level. To study the impact of using metabolic factors as normalising parameter for scaling dialysis dose on survival outcome, a large-scale longitudinal study was conducted with 1500 maintenance haemodialysis patients recruited for the study. Dialysis dose-related parameters and survival outcomes were collected at baseline and at various time points during the follow-up period of 18 months. Study results were analysed in two parts - the theoretical basis for using these metabolic factors as scaling parameters was explored which showed that current minimum target dialysis dose risks under-dialysis in certain subgroups of patients and using these alternative parameters may provide a more equivalent dialysis dose across individuals of different body sizes and gender. With these results arguing for potential use of the alternative parameters, the impact on survival of using them were examined. It was found that all three parameters performed better than the current parameter (total body water) with regards to predicting mortality. Total energy expenditure was found to be the best parameter with the lowest hazard ratio for risk of death. The study data was also analysed to derive an algorithm for adjustment of minimum target dialysis dose based on body size and physical activity level. This newly derived minimum dose target was also shown to impact on survival with those underdialysed based on this criteria having poorer survival outcomes. To understand the impact of whole body protein turnover on resting energy expenditure and uraemic toxin generation, a cross-sectional study was conducted on 12 patients with advanced CKD – 6 each in pre-dialysis CKD and haemodialysis group. It was found that haemodialysis patients had higher rate of protein turnover compared to pre-dialysis patients. Whole body protein turnover was found to contribute significantly to resting energy expenditure and had a moderately strong relationship with urea generation rate. In the course of these studies, two questionnaire tools have been validated for use for clinical and research purposes – one is a self-report comorbidity questionnaire and the other, the Recent Physical Activity Questionnaire. The comorbidity questionnaire was developed as part of this work and was validated against Charlson Comorbidity Index. The Recent Physical Activity Questionnaire was validated for physical activity data collection and energy expenditure calculation against the gold-standard doubly labelled water method. In conclusion, it has been demonstrated that metabolic factors such as body surface area, resting energy expenditure and total energy expenditure are more closely related to uraemic toxin generation compared to total body water. It has also been demonstrated that physical activity contributes to metabolic waste production and may necessitate changes in dialysis requirement. It has been shown that these metabolic factors, when used as scaling parameter for dialysis dosing, may predict survival better than the current parameter in use. The algorithm for dialysis dose adjustment and the questionnaires validated in this work have provided novel tools for further research studies and clinical practice. The central hypothesis of this work is that some metabolic factors may be better markers of uraemic toxin generation compared to total body water. It is hypothesised that modifications in dialysis practice based on these factors may improve the quality of haemodialysis and favourably impact on survival outcome for patients with end-stage renal disease. The work presented here largely supports this hypothesis

A single weekly Kt/Vurea target for peritoneal dialysis patients does not provide an equal dialysis dose for all

Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.Dialysis adequacy is traditionally based on urea clearance, adjusted for total body volume (Kt/Vurea), and clinical guidelines recommend a Kt/Vurea target for peritoneal dialysis. We wished to determine whether adjusting dialysis dose by resting and total energy expenditure would alter the delivered dialysis dose. The resting and total energy expenditures were determined by equations based on doubly labeled isotopic water studies and adjusted Kturea for resting energy expenditure and total energy expenditure in 148 peritoneal dialysis patients (mean age, 60.6 years; 97 male [65.5%]; 54 diabetic [36.5%]). The mean resting energy expenditure was 1534 kcal/d, and the total energy expenditure was 1974 kcal/day. Using a weekly target Kt/V of 1.7, Kt was calculated using V measured by bioimpedance and the significantly associated (r = 0.67) Watson equation for total body water. Adjusting Kt for resting energy expenditure showed a reduced delivered dialysis dose (ml/kcal per day) for women versus men (5.5 vs. 6.2), age under versus over 65 years (5.6 vs. 6.4), weight 80 kg (5.8 vs. 6.1), low versus high comorbidity (5.9 vs. 6.2), all of which were significant. Adjusting for the total energy expenditure showed significantly reduced dosing for those employed versus not employed (4.3 vs. 4.8), a low versus high frailty score (4.5 vs. 5.0) and nondiabetic versus diabetic (4.6 vs. 4.9). Thus, the current paradigm for a single target Kt/Vurea for all peritoneal dialysis patients does not take into account energy expenditure and metabolic rate and may lead to lowered dialysis delivery for the younger, more active female patient.Peer reviewedFinal Accepted Versio

Characteristics of Frailty in Haemodialysis Patients

© The Author(s) 2022. This article is distributed under the terms of the Creative Commons Attribution-Non Commercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/Background: Both frailty and cachexia increase mortality in haemodialysis (HD) patients. The clinical frailty score (CFS) is a seven-point scale and less complex than other cachexia and frailty assessments. We wished to determine the characteristics of frail HD patients using the CFS.  Methods: Single centre cross-sectional study of HD patients completing physical activity questionnaires with bioimpedance measurements of body composition and hand grip strength (HGS).  Results: We studied 172 HD patients. The CFS classified 54 (31.4%) as frail, who were older (70.4±12.2 vs 56.2 ± 16.1 years, p < 0.001), greater modified Charlson co-morbidity (3 (2–3) versus 1.5 (0–3), p < 0.001), and body fat (33 (25.4–40.2) versus 26.2 (15.8–34) %, p < 0.01), but lower total energy expenditure (1720 (1574–1818) versus 1870 (1670–2194) kcal/day, p < 0.01), lean muscle mass index (9.1 (7.7–10.1) versus 9.9 (8.9–10.8) kg/m2), and HGS (15.3 (10.3–21.9) versus 23.6 (16.7–34.4) kg), both p < 0.001. On multivariable logistic analysis, frailty was independently associated with lower active energy expenditure (odds ratio (OR) 0.98, 95% confidence limits (CL) 0.98–0.99, p = 0.001), diabetes (OR 5.09, CL 1.06–16.66) and HGS (OR 0.92, CL 0.86–0.98).  Discussion: Frail HD patients reported less active energy expenditure, associated with reduced muscle mass and strength. Frail patients were more likely to have greater co-morbidity, particularly diabetes. Whether physical activity programmes can improve frailty remains to be determined.Peer reviewedFinal Published versio

Indexing dialysis dose for gender, body size and physical activity: Impact on survival

Current practice basing dialysis dose on urea distribution volume (V) has been questioned. We explored the impact on survival of scaling dialysis dose (Kt) to parameters reflective of metabolic activity. In a multicentre prospective cohort study of 1500 patients on thrice-weekly haemodialysis, body surface area (BSA) and resting energy expenditure (REE) were estimated using validated equations and physical activity by the Recent Physical Activity Questionnaire. Total energy expenditure (TEE) was estimated from REE and physical activity data. Kt was calculated from delivered (single-pool Kt/V)*Watson V. Kt/BSA, Kt/ REE and Kt/TEE were then calculated at baseline and 6 monthly during follow-up for 2 years. In adjusted Cox models Kt/TEE, Kt/BSA, Kt/REE, in that order, had lower hazard ratios for death than single-pool Kt/V. On the basis of adjusted survival differences, putative minimum target doses were estimated for Kt/BSA as 27119 ml/m 2 and Kt/TEE as 25.79 ml/ kcal. We identified spKt/V values equivalent to these estimated targets, ranging from 1.4 to 1.8 in patient groups based on gender, body size and physical activity. For sedentary patients, the minimum target dose was 1.4 for large males, 1.5 for small males and 1.7 for women. For active patients the target was 1.8 irrespective of gender and body-weight. Patients achieving these individualised minimum targets had greater adjusted two-year survival compared to those achieving conventional minimum targets. Metabolic activity related parameters, such as Kt/TEE and Kt/BSA, may have a clinically important role in scaling haemodialysis dose. Using such parameters or their spKt/V equivalents to adjust minimum target doses based on gender, body size and habitual physical activity may have a positive impact on survival.Peer reviewe

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

© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.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.Peer reviewedFinal Accepted Versio

Multi-disciplinary team-based simulation training in acute care settings: a systematic review of the impact on team performance

© 2022 The Authors. Published by Journal of Surgical Simulation. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial 4.0 International License (CC BY-NC), https://creativecommons.org/licenses/by-nc/4.0/Background: Teamwork plays an essential role in providing quality health care and ensuring good outcomes and safe practices in any health care system. This has been demonstrated in several studies in emergency care where resuscitation teams perform at a high level to achieve desired outcomes in life-threatening situations. Simulation has been identified as an effective way of improving team performance skills, especially in acute care settings where team dynamics change rapidly and require good collaboration. In addition to clinical competence, the members of the team need to be conversant with non-technical skills such as team leadership and communication. Methods: The MEDLINE, EMBASE and Cochrane Library databases were searched for original articles from the last 20 years investigating team performance in multi0disciplinary team-based simulation training in acute care settings. The research questions were developed using the participants, intervention, comparisons, outcome (PICO) framework. The review was designed and reported in accordance with PRISMA guidelines. The articles were then assessed by independent reviewers using the Critical Appraisal Skills Program (CASP) to standardize the assessment process. Results: Of the 1260 articles identified, 12 primary research articles representing a variety of team-based simulation training in various acute care settings were included. The studies were published between 2002 and 2020 and included 679 participants 418 years of age. All articles were original research papers with a combination of pre-/post-test, observational, randomized, and prospective designs; 11 were single-site studies and one was a multi-site study. Six studies used a pre-/post-test interventional method, four used a post-interventional method and one was an observational study. One study used a prospective blinded controlled observational method. Most of the articles reviewed did not provide high-level evidence and the control aspect of PICO was not applied because the review focused mainly on the intervention and outcome with no comparator. This study shows that 72.2% of the reviewed articles demonstrated a positive impact of team-based simulation training on team performance. Discussion: This review has demonstrated some evidence that team-based simulation training used in various emergency and acute care clinical settings does improve team performance. However, how that translates to improvement in patient safety and clinical outcomes was not fully addressed by most of the articles reviewed and other previous studies. Simulation enhances team training; the evidence to support multi-disciplinary team training is positive although limited and will require further research to fully develop and validate simulation-based team training programmes.Peer reviewe

Impact of incremental versus conventional initiation of haemodialysis on residual kidney function : study protocol for a multicentre feasibility randomised controlled trial

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.INTRODUCTION: Preserving residual kidney function (RKF) may be beneficial to patients on haemodialysis (HD) and it has been proposed that commencing dialysis incrementally rather than three times a week may preserve RKF. In Incremental HD, target dose includes a contribution from RKF, which is added to HD dose, allowing individualisation of the HD prescription. We will conduct a feasibility randomised controlled trial (RCT) comparing incremental HD and conventional three times weekly treatments in incident HD patients. The study is designed also to provide pilot data to allow determination of effect size to power a definitive study. METHODS AND ANALYSIS: After screening to ensure native renal urea clearance >3 mL/min/1.73 m2, the study will randomise 54 patients within 3 months of HD initiation to conventional in-centre thrice weekly dialysis or incremental in-centre HD commencing 2 days a week. Subjects will be followed up for 12 months. The study will be carried out across four UK renal centres.The primary outcome is to evaluate the feasibility of conducting a definitive RCT and to estimate the difference in rate of decline of RKF between the two groups at 6 and 12 months time points. Secondary outcomes will include the impact of dialysis intensity on vascular access events, major adverse cardiac events and survival. Impact of dialysis intensity on patient-reported outcomes measures, cognition and frailty will be assessed using EQ-5D-5L, PHQ-9, Illness Intrusiveness Rating Score, Montreal Cognitive assessment and Clinical Frailty Score. Safety outcomes include hospitalisation, fluid overload episodes, hyperkalaemia events and vascular access events.This study will inform the design of a definitive study, adequately powered to determine whether RKF is better preserved after incremental HD initiation compared with conventional initiation. ETHICS AND DISSEMINATION: Ethics approval has been granted by Cambridge South Research Ethics Committee, United Kingdom(REC17/EE/0311). Results will be disseminated via peer-reviewed publication. TRIAL REGISTRATION NUMBER: NCT03418181.Peer reviewedFinal Published versio

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 haemodialysis (HD) have reduced survival. This may be due to the practice of using total body water (V) as the normalising factor for dialysis dosing. Our aim in this study was to explore the use of alternate parameters for scaling dialysis dose. Study Design: Prospective, cross-sectional study. Setting and Participants: 1500 HD patients on thrice weekly schedule were recruited across five different centres. Predictors: Age, sex, weight, ethnicity, comorbidity level and employment status. Outcomes: Kt was estimated by multiplying V by 1.2. Kt/BSA, Kt/REE and Kt/TEE equivalent to a target Kt/V of 1.2 were then estimated by dividing Kt by the respective parameters. Measurements: Anthropometric and HD adequacy details were obtained from direct measurements and medical records of patients. Body surface area (BSA) was estimated using Haycock formula. Resting energy expenditure (REE) was estimated using a novel validated equation. Total energy expenditure (TEE) was calculated from physical activity data obtained using Recent Physical Activity Questionnaire. Results: Mean BSA was 1.87 m2, mean REE 1545 kcal/day and mean TEE 1841 kcal/day. For Kt/V of 1.2, there was a wide range of equivalent doses expressed as Kt/BSA, Kt/REE and Kt/TEE. The mean equivalent dose was lower in women for all 3 parameters (p<0.001). Small men would also receive lower doses compared to larger men. Younger patients, those with low comorbidity, those employed and those of South Asian ethnicity would receive significantly lower dialysis doses with current practice. Limitations: Cross-sectional study and the physical activity data has been collected by an activity questionnaire. Conclusion:Our data suggest that current dosing practices risk under-dialysis in women and men of lower body size and in specific subgroups of patients. Using BSA, REE or TEE based dialysis prescription would result in higher dose delivery in these patients

A self-report comorbidity questionnaire for haemodialysis patients

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise statedBackground: 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 R2value 0.202), with a predictive power similar to that of the CCI (Nagelkerke R2value 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.Peer reviewe