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Dialysis adequacy is traditionally based on urea clearance, ore than 3 million patients with end-stage kidney
adjusted for total body volume (Kt/Vurea), and clinical disease are currently treated by dialysis worldwide,
guidelines recommend a Kt/Vurea target for peritoneal with w300,000 treated by peritoneal dialysis (PD).
dialysis. We wished to determine whether adjusting dialysis As with hemodialysis, there are clinical guidelines recommend-
dose by resting and total energy expenditure would alter ing that patients receive a minimal amount of dialysis based on
the delivered dialysis dose. The resting and total energy urea clearance.1 These urea-based clearance targets are derived
expenditures were determined by equations based on from observational studies.2 However, prospective studies
doubly labeled isotopic water studies and adjusted Kturea comparing different peritoneal dialysis regimens designed to
for resting energy expenditure and total energy achieve different urea clearance targets consistently failed to
expenditure in 148 peritoneal dialysis patients (mean age, demonstrate any advantage for greater urea clearance in terms
60.6 years; 97 male [65.5%]; 54 diabetic [36.5%]). The mean of patient morbidity or mortality.3–5 Indeed, PD technique and
resting energy expenditure was 1534 kcal/d, and the total patient survival have been linked to preservation of residual
energy expenditure was 1974 kcal/day. Using a weekly renal function6 rather than PD urea clearance.7
target Kt/V of 1.7, Kt was calculated using V measured by The amount of urea clearance (Kt/Vurea) for dialysis patients
bioimpedance and the significantly associated (r [ 0.67) is currently based on the volume of distribution of urea, total body
Watson equation for total body water. Adjusting Kt for water (TBW) derived from anthropomorphic measurements.8
resting energy expenditure showed a reduced delivered However, TBW varies with body composition, as some tissues
dialysis dose (ml/kcal per day) for women versus men (5.5 such as muscle contain more water than fat,9 and also varies
vs. 6.2), age under versus over 65 years (5.6 vs. 6.4), between racial groups10 and patients with diabetes and other
weight <65 versus >80 kg (5.8 vs. 6.1), low versus high comorbidities.11 As such, for the same Kt/Vurea, the delivered
comorbidity (5.9 vs. 6.2), all of which were significant. urea clearance has been suggested to differ among patients.12
Adjusting for the total energy expenditure showed Rather than dosing the amount of dialysis required on urea
significantly reduced dosing for those employed versus not clearance based on volume of distribution, an alternative
employed (4.3 vs. 4.8), a low versus high frailty score approach based on metabolic activity has been proposed.13
(4.5 vs. 5.0) and nondiabetic versus diabetic (4.6 vs. 4.9). Urea is generated as a by-product of intracellular nitrogen
Thus, the current paradigm for a single target Kt/Vurea for metabolism. Total body metabolic activity is a composite of
all peritoneal dialysis patients does not take into account resting metabolic rate and that due to physical activity. Pre-
energy expenditure and metabolic rate and may lead to vious studies in PD patients have concentrated on measuring
lowered dialysis delivery for the younger, more active resting energy expenditure (REE).14,15 but this underestimates
female patient. total energy expenditure (TEE), by excluding that due to
Kidney International (2016) -, -–-; http://dx.doi.org/10.1016/ activity energy expenditure.
j.kint.2016.07.027 We recently validated an assessment of TEE and REE in
KEYWORDS: body surface area; Kt/Vurea; peritoneal dialysis; resting energy dialysis patients using a patient self-reported questionnaire
expenditure; total body water; total energy expenditure and doubly labeled isotopic water.16,17 To establish whether
Copyright ª 2016, International Society of Nephrology. Published by there is a difference in the amount of dialysis delivered for a
Elsevier Inc. All rights reserved.
fixed Kt/Vurea target, we calculated urea clearance adjusted
for energy expenditure to determine whether some groups of
patients would be at a disadvantage under current clinical
guideline recommendations.
Correspondence: Andrew Davenport, UCL Centre for Nephrology, Royal Free
Hospital, University College London Medical School, Rowland Hill Street, RESULTS
London NW3 2PF, United Kingdom. E-mail: andrewdavenport@nhs.net We studied 148 adult PD patients with a mean calculated REE
Received 29 April 2016; revised 11 July 2016; accepted 14 July 2016 of 1534 241 kcal/d and TEE 1974 414 kcal/d (Table 1).
Table 1 | Patient demographic characteristics, peritoneal Table 2 | Estimates of daily REE and TEE in patients according
dialysis prescription, results of peritoneal dialysis adequacy, to age, comorbidity, frailty, and ethnicity groupings
and transport status in all patients and those with
Variable REE, kcal/d TEE, kcal/d
contemporaneous bioimpedance measurements
Male 1597 217 2029 423
Variable Total Cohort Bioimpedance Group Female 1412 2401 1868 3772
N 148 118 Age <65 yr 1646 209 2173 392
Male, % 65.5 63.6 Age >65 yr 1408 2111 1750 3141
Age, yr 60.6 17.5 59.5 18.2 Nondiabetic 1522 233 2021 435
Weight, kg 73.6 16.7 73.1 16.6 Diabetic 1556 254 1893 3662
Body surface area, m2 1.86 0.24 1.85 0.24 Employed 1577 237 2305 511
White 43.2 42.4 Unemployed 1523 242 1890 3401
African/Afro-Caribbean 24.3 21.1 Low comorbidity 1532 245 2012 441
South Asian 27.7 29.7 High comorbidity 1539 231 1862 300
East Asian 5.4 6.8 Low frailty score 1533 227 2049 453
Employed 20.3 22.9 High frailty score 1535 256 1894 3532
Dialysis vintage, mo 9.1 (3.5–25.2) 9.4 (3.8–25.5) Weight <64 kg 1305 151 1706 306
Comorbidity score 4.0 (0–6.0) 4.0 (0–6.0) Weight 64–80 kg 1514 1421 1973 4141
Heart disease, % 19.7 19.7 Weight >80 kg 1775 1591 2233 3391
Myocardial infarction, % 10.2 9.4 PNA <60 g/d 1450 214 1826 317
Diabetes mellitus, % 32.4 29.7 PNA >60 g/d 1622 2291 2133 4381
Frailty 3.0 (3.0–4.0) 3.0 (3.0–4.0) Non-Asian 1561 225 2060 462
Hemoglobin, g/l 109.9 4.8 110.5 4.5 Asian 1522 243 1866 3592
Serum albumin, g/l 36.5 5.5 36.6 5.6 REE, energy expenditure; TEE, total energy expenditure; PNA, protein nitrogen
C-reactive protein, mg/l 5.0 (2.0–16.8) 5.0 (2.0–15.0) appearance.
Serum glucose, mmol/l 5.9 (4.9–8.5) 5.7 (4.9–5.1) Daily PNA g/d. Results expressed as mean SD.
IFCC, mmol/mg 38.4 (33.3–51.4) 36.2 (32.7–47.5)
1
P < 0.01 comparing groups, adjusted for multiple comparisons (Bonferroni
Serum cholesterol, mmol/l 4.47 1.44 4.50 1.50 method).
2
P < 0.05, adjusted for multiple comparisons (Bonferroni method).
Serum urea, mmol/l 18.4 6.1 18.5 5.9
Serum creatinine, mmol/l 698 (523–871) 696 (525–909)
Peritoneal cycler, % 85.5 83.9
Icodextrin use, % 75.7 81.2 P < 0.001 for men), BSA was relatively greater at lower TBW
Icodextrin volume, l/d 1.8 (0.5–2.0) 1.8 (1.0–2.0) volumes and relatively lower at higher TBW volumes. TBW
22.7–23.0 glucose use, % 57.4 54.2 had also measured by bioimpedance at the time of adequacy
22.7–23.0 glucose, l/d 2.5 (0–5.0) 2.9 (0–6)
Previous peritonitis episodes 0 (0–1) 0 (0–1) testing in 118 of the patients (79.7%) (Table 1). There was
Total weekly Kt/Vurea 2.1 (1.7–2.6) 2.1 (1.7–2.60) no statistically significant difference in TBW: Watson equa-
Weekly urinary Kt/Vurea 0.8 (0.3–1.3) 0.9 (0.3–1.4) tion, 40.3 6.1 versus bioimpedance, 40.6 3.4 L; mean
Weekly peritoneal Kt/Vurea 1.2 (0.9–1.6) 1.2 (0.8–1.6)
difference on Bland-Altman analysis, 0.72 L (Figure 1).
Total creatinine cleared 67.4 (55.8–84.7) 70.1 (55.8–86.7)
per week/1.73 m2 Although the mean difference for women was 1.43 L and
Urine creatinine cleared 29.6 (13.4–58.4) 28.9 (12.7–59.4) that for men was 0.31 L, the 95% limits of agreement were
per week/1.73 m2, L broad; 9.20 to 10.16 L for women, and from 11.04 to
Peritoneal creatinine cleared 35.6 (23.2–45.2) 37.3 (23.5–49.3)
per week/1.73 m2, L
11.66 L for men. There were positive correlations between
Urine <100 ml/d, % 12.2 15.3 BSA and both REE and TEE (r ¼ 0.92, P < 0.001 and r ¼
Urine volume, ml/d 946 (450–1249) 940 (448–1408) 0.59, P < 0.001, respectively) and also between TBW and
4-hr dialysate/plasma creatinine 0.71 0.11 0.73 0.11 both REE and TEE (r ¼ 0.85, P < 0.001 and r ¼ 0.66,
24-hr ultrafiltrate, ml 566 (200–908) 536 (192–899)
Protein nitrogen appearance, 0.89 0.26 0.89 0.25
P < 0.001, respectively).
g/kg per day Clinical guidelines have recommended a minimal weekly
IFCC ¼ International Federation of Clinical Chemists. Kt/Vurea of 1.7. We then calculated Kt values for a weekly Kt/
Values shown as number, mean SD, median (interquartile range), and percentage. Vurea of 1.7 using both Watson equation and bioimpedance
estimates of TBW. These Kt values were then adjusted by BSA,
Twenty-five percent were classified as high comorbidity18 and REE, and TEE. There was a positive relationship between
48% as frail.19 Male patients were heavier than female patients TBW and Kt/TEE (Figure 2). The results of the adjusted Kt
and had a greater REE and TEE (Table 2). Patients who were dialysis dosing are shown in Table 3 and Figure 3 for different
employed, those with greater weight, and greater protein ni- patient groups. For the same prescribed dialysis dose
trogen appearance (PNA) had a higher TEE (Table 2), (Kturea), women, younger patients, patients who were
whereas those with greater frailty and comorbidity, those who employed, and patients weighing less (Figure 3) received less
were diabetic, and those who were Asian tended to have a dialysis than men, older patients, unemployed patients, and
lower TEE. heavier patients (Table 3). In addition, patients with fewer
As previous studies have suggested that Kt be adjusted for comorbidities and less frailty, nondiabetic patients, and pa-
body surface area (BSA), we compared Watson TBW with tients of non-Asian races also tended to receive less dialysis
BSA. Although there was a strong association between TBW than those with more comorbidities and those who were
and BSA (r2 ¼ 0.99, P < 0.001 for women and r2 ¼ 0.83, diabetic, frail, and of Asian ethnicity.
Table 3 | Comparison of a fixed total weekly Kt/V of 1.7 (urea clearance l/m2 per day or ml/kcal per day) adjusted for BSA, REE,
and TEE for peritoneal dialysis patients comparing sexes, age, diabetic/nondiabetic, employment status, comorbidity, weight,
ethnicity, high and low frailty, comorbidity, PNA rate, employed, unemployed, and ethnicity (Asian vs. other races)
Variable Kt/BSA Kt/REEW Kt/TEEW Kt/REEBIA Kt/TEEBIA
Male 5.13 0.36 6.15 9.61 4.96 0.71 6.23 0.62 4.93 0.70
Female 4.42 0.401 5.50 0.411 4.23 0.651 5.64 0.641 4.27 0.711
Age <65 yr 4.83 0.46 5.58 0.55 4.29 0.53 5.93 0.73 4.52 0.81
Age >65 yr 4.95 0.42 6.38 0.491 5.18 0.611 6.12 0.62 4.93 0.651
Diabetic 4.96 0.45 6.03 0.58 5.00 0.691 5.92 0.65 4.93 0.692
Nondiabetic 4.84 0.46 5.90 0.66 4.53 0.82 6.06 0.71 4.57 0.78
High frailty 4.91 0.47 6.06 0.66 4.96 0.75 6.01 0.61 4.90 0.71
Low frailty 4.86 0.43 5.85 0.602 4.46 0.781 6.01 0.75 4.54 0.781
High comorbidity 4.99 0.43 6.19 0.63 5.14 0.66 5.91 0.63 4.90 0.63
Low comorbidity 4.85 0.45 5.87 0.621 4.55 0.801 6.05 0.71 4.62 0.81
Unemployed 4.89 0.43 5.99 0.61 4.87 0.72 5.96 0.73 4.81 0.75
Employed 4.89 0.54 5.82 0.71 4.07 0.821 6.19 0.51 4.31 0.721
High PNA rate 4.79 0.40 5.91 0.62 4.75 0.78 5.77 0.70 4.56 0.70
Low PNA rate 4.95 0.482 5.98 0.68 4.62 0.87 6.23 0.592 4.81 0.81
Asian 4.87 0.46 5.97 0.65 4.67 0.85 6.10 0.65 4.71 0.76
Other 4.87 0.42 5.90 0.60 4.79 0.69 5.79 0.762 4.64 0.80
BIA, bioimpedance; BSA, body surface area; DM, diabetic; REE, resting energy expenditure; TEE, total energy expenditure; W, Watson formula.
Volume (V) was estimated by the Watson formula or measured by BIA.
1
P < 0.01 after Bonferroni post hoc correction for multiple testing.
2
P < 0.05 after Bonferroni post hoc correction for multiple testing.
There are a number of limitations that should be consid- as a surrogate for dietary protein intake, these estimates may
ered. We used solely a weekly target Kt/Vurea, whereas some not be as reliable for patients with increasing comorbidity,
guidelines additionally recommend liters of creatinine cleared and we did not formally estimate dietary protein intake.
as an additional target for PD patients, and there may be Although we accepted that using Kt/Vurea for dialysis dosing
differences between these targets depending on use of PD has some limitations,28 more recent observational studies have
cyclers, and the amount of residual renal function.1,24 We suggested an advantage for adjusting Kt for BSA.23 We found
adjusted Kt using both the Watson equation and bio- that adjusting for BSA detected a difference between men and
impedance. There were some differences between these women and in relation to body weight and PNA. However,
methods. The Watson equation was established using a adjusting for TEE additionally demonstrated that younger and
healthy population, whereas PD patients have increased more fit patients, employed patients, and patients with less
TBW.25 As such, bioimpedance measurements are preferable, comorbidity received a relatively lower delivered dialysis dose
but ideally should be measured with the peritoneal dialysate compared with older, more frail, comorbid, and diabetic pa-
drained.26 In addition, we calculated PNA rates using equa- tients. Although we chose to investigate the effect of a weekly
tions developed in a previous era, when patients were pre- target Kt/Vurea of 1.7, our findings would be equally applicable
dominantly treated by continuous ambulatory PD and to any set Kt/V target applied to patients. Therefore, we suggest
glucose-only dialysates,27 and although these are often used that a single Kt/Vurea target dose is not applicable to all patients,
and the dose of dialysis should be increased for those who are
more physically active with greater TEE. On the other hand, the
results of our study should not be misinterpreted to imply that
some patient groups require less dialysis treatment. Our results
generate a hypothesis that requires formal testing to determine
whether increasing the minimum target dose of dialysis in some
groups of PD patients improves patient outcomes.
Table 4 | Multivariable step backward models for weekly Kt expenditure in patients with chronic kidney disease.16 Phys-
adjusted for BSA, REE, TEE using both total body water ical activity data were determined by each reported activity
calculated by Watson equation and measured by BIA, being assigned a metabolic equivalent of task (MET) value
unstandardized b, SE, standardized b, and 95% CL according to the Compendium of Physical Activities.31 The
Standardized equations for calculating REE and TEE are detailed in the
Variable b SE b b t 95% CL P Value Supplementary Appendix.
Kturea/BSA UK clinical guidelines recommend a minimum weekly Kt/
Male 0.70 0.05 0.77 13.5 0.6, 0.87 <0.001 Vurea of 1.7.1,32 Hence, in order to compare minimum
Kturea/REEW dialysis targets using alternative scaling parameters, weekly Kt
Male 0.58 0.08 0.44 7.5 0.43, 0.74 <0.001
Age, yr 0.02 0.01 0.54 9.3 0.2, 0.25 <0.001 was calculated as Kt ¼ 1.7 multiplied by V. Corresponding
Kturea/REEBIA target values of Kt/BSA, Kt/REE, and Kt/TEE were calculated
PNA rate 0.01 0.01 0.37 4.4 0.01, 0.02 <0.001 by dividing daily Kt by the respective parameters.
Male 0.39 0.12 0.28 3.2 0.15, 0.63 0.002
Ethical approval of the study was granted by the UK Na-
Age, yr 0.01 0.01 0.19 2.3 0.01, 0.01 0.025
Kturea/TEEW tional Research Ethics Committee–Essex, and the study was
Male 0.59 0.10 0.35 6.1 0.40, 0.79 <0.001 registered in UK Clinical Research Network portfolio number
Age, yr 0.02 0.01 0.44 7.5 0.02, 0.013 <0.001 14018. All patients provided written informed consent in
Unemployed 0.52 0.11 0.26 4.5 0.29, 0.74 <0.001
High comorbidity 0.30 0.11 0.16 2.7 0.01, 0.52 0.009
keeping with the Declaration of Helsinki.
Diabetic 0.21 0.10 0.12 2.0 0.01, 0.41 0.045
Kturea/TEEBIA Statistical analysis
Male 0.51 0.13 0.33 3.8 0.25, 0.77 <0.001
Statistical analysis was performed using the Student t test or
Age, yr 0.01 0.01 0.32 7.5 0.01, 0.02 <0.001
Unemployed 0.44 0.15 0.24 3.0 0.15, 0.74 0.004 Mann-Whitney U test, analysis of variance, the Kruskal-Wallis
BIA, bioimpedance; BSA, body surface area; CL, confidence limits; PNA, protein ni-
test with appropriate post hoc correction, the Pearson or
trogen accumulation; REE, resting energy expenditure; TEE, total energy expenditure; Spearman test for univariate correlation (GraphPad Prism,
W, Watson equation. version 6.0, San Diego, CA), and step backward linear
BSA model, r2 0.60 adjusted, 0.59; model adjusted for REEW, r20.60; adjusted 0.59; model
adjusted for REEBIA r20.42; adjusted, 0.37. Model adjusted for TEEW r20.42, adjusted 0.3, regression of variables on univariate analysis of P < 0.1 and
and adjusted for TEEBIA r20.35, adjusted 0.33. Sex (female vs. male). those considered to be clinically relevant, with log trans-
formation of variables that were not normally distributed and
computerized hospital records, and comorbidity was deter- removal of variables that were not statistically significant
mined using self-administered comorbidity grading18 based unless they improved model fit. Models were checked for
on medical conditions and complications including diabetes collinearity using SPSS, version 22 (SPSS Inc., Chicago, IL)
mellitus (as defined by WHO criteria), cardiac disease, res- and the Bland-Altman comparison (Analyse-It Software,
piratory disease, liver disease, arthritis, depression, malig- version 3.0, Leeds, UK). Data are presented as the mean
nancy, and a frailty score previously reported in patients with SD, median (interquartile range), mean and 95% confidence
chronic kidney disease.19 We defined a high comorbidity limits (CL), or percentage.
score as $4.0 and a high frailty score $4.0, in keeping with
previous studies.18,19 DISCLOSURE
TBW was calculated using the Watson equation.8 In All the authors declared no competing interests.
addition, in 118 of the patients, contemporaneous measure-
ments of TBW made with bioimpedance (InBody 720, ACKNOWLEDGMENTS
InBody, Seoul, South Korea; Body Composition Monitor, The study was funded by a grant from the British Renal Society. SE-K
Fresenius, Bad Homberg, Germany), which had been per- was awarded an International Society for Nephrology fellowship.
formed in a standardized manner,28,29 were available for re-
view. Bioimpedance measurements made by the Body SUPPLEMENTARY MATERIAL
Composition Monitor and InBody were standardized using Supplementary Appendix. Resting energy expenditure (REE) was
previously derived equations.30 BSA was calculated using the estimated from a newer novel predictive equation that was derived
Gehan and George equation, as recommended by the Euro- and validated in a cohort of hemodialysis patients.18
pean Best Clinical Practice guidelines.24 Supplementary material is linked to the online version of the paper at
Physical activity data were obtained using the Recent www.kidney-international.org.
Physical Activity Questionnaire,16 which collects information
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