A single weekly Kt/Vurea target for peritoneal dialysis patients does not provide an equal dialysis dose for all
2016; Elsevier BV; Volume: 90; Issue: 6 Linguagem: Inglês
10.1016/j.kint.2016.07.027
ISSN1523-1755
AutoresSally El‐Kateb, Sivakumar Sridharan, Ken Farrington, Stanley Fan, Andrew Davenport,
Tópico(s)Muscle and Compartmental Disorders
ResumoDialysis 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. 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. More than 3 million patients with end-stage kidney disease are currently treated by dialysis worldwide, with ∼300,000 treated by peritoneal dialysis (PD). As with hemodialysis, there are clinical guidelines recommending that patients receive a minimal amount of dialysis based on urea clearance.1Woodrow G, Davies SJ. Peritoneal Dialysis (PD) (Guidelines PD 3.1 – 3.3). Available at: http://www.renal.org/guidelines/modules/peritoneal-dialysis-in-ckd#sthash.Br67xjah.dpuf. Accessed July 25, 2016.Google Scholar These urea-based clearance targets are derived from observational studies.2Jansen M.A. Termorshuizen F. Korevaar J.C. et al.Predictors of survival in anuric peritoneal dialysis patients.Kidney Int. 2005; 68: 1199-1205Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar However, prospective studies comparing different peritoneal dialysis regimens designed to achieve different urea clearance targets consistently failed to demonstrate any advantage for greater urea clearance in terms of patient morbidity or mortality.3Paniagua R. Amato D. Vonesh E. et al.Mexican Nephrology Collaborative Study GroupEffects of increased peritoneal clearances on mortality rates in peritoneal dialysis: ADEMEX, a prospective, randomized, controlled trial.J Am Soc Nephrol. 2002; 13: 1307-1320Crossref PubMed Scopus (1576) Google Scholar, 4Lo W.K. Ho Y.W. Li C.S. et al.Effect of Kt/V on survival and clinical outcome in CAPD patients in a randomized prospective study.Kidney Int. 2003; 64: 649-656Abstract Full Text Full Text PDF PubMed Scopus (217) Google Scholar, 5Paniagua R. Amato D. Vonesh E. et al.Mexican Nephrology Collaborative Study GroupHealth-related quality of life predicts outcomes but is not affected by peritoneal clearance: the ADEMEX trial.Kidney Int. 2005; 67: 1093-1104Abstract Full Text Full Text PDF PubMed Scopus (82) Google Scholar Indeed, PD technique and patient survival have been linked to preservation of residual renal function6Churchill D.N. Taylor D.W. Keshaviah P.R. Adequacy of dialysis and nutrition in continuous peritoneal dialysis: association with clinical outcome.J Am Soc Nephrol. 1996; 7: 198-207PubMed Google Scholar rather than PD urea clearance.7Bargman J.M. Thorpe K.E. Churchill D.N. CANUSA Peritoneal Dialysis Study GroupRelative contribution of residual renal function and peritoneal clearance to adequacy of dialysis: a reanalysis of the CANUSA study.J Am Soc Nephrol. 2001; 12: 2158-2162Crossref PubMed Google Scholar The amount of urea clearance (Kt/Vurea) for dialysis patients is currently based on the volume of distribution of urea, total body water (TBW) derived from anthropomorphic measurements.8Watson P.E. Watson I.D. Batt R.D. Total body water volume for adult males and females estimated from simple anthropometric measurements.Am J Clin Nutr. 1980; 33: 27-39Crossref PubMed Google Scholar However, TBW varies with body composition, as some tissues such as muscle contain more water than fat,9Davenport A. Differences in prescribed Kt/V and delivered haemodialysis dose–why obesity makes a difference to survival for haemodialysis patients when using a 'one size fits all' Kt/V target.Nephrol Dial Transplant. 2013; 28: iv219-iv223Crossref PubMed Scopus (41) Google Scholar and also varies between racial groups10Davenport A. Hussain Sayed R. Fan S. The effect of racial origin on total body water volume in peritoneal dialysis patients.Clin J Am Soc Nephrol. 2011; 6: 2492-2498Crossref PubMed Scopus (31) Google Scholar and patients with diabetes and other comorbidities.11Davenport A. Willicombe M.K. Does diabetes mellitus predispose to increased fluid overload in peritoneal dialysis patients?.Nephron Clin Pract. 2010; 114: c60-c66Crossref PubMed Scopus (45) Google Scholar As such, for the same Kt/Vurea, the delivered urea clearance has been suggested to differ among patients.12Spalding E.M. Chandna S.M. Davenport A. Farrington K. Kt/V underestimates the haemodialysis dose in women and small men.Kidney Int. 2008; 74: 348-355Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar Rather than dosing the amount of dialysis required on urea clearance based on volume of distribution, an alternative approach based on metabolic activity has been proposed.13Daugirdas J.T. Levin N.W. Kotanko P. et al.Comparison of proposed alternative methods for rescaling dialysis dose: resting energy expenditure, high metabolic rate organ mass, liver size, and body surface area.Semin Dial. 2008; 21: 377-384Crossref PubMed Scopus (44) Google Scholar Urea is generated as a by-product of intracellular nitrogen metabolism. Total body metabolic activity is a composite of resting metabolic rate and that due to physical activity. Previous studies in PD patients have concentrated on measuring resting energy expenditure (REE).14Bazanelli A.P. Kamimura M.A. da Silva C.B. et al.Resting energy expenditure in peritoneal dialysis patients.Perit Dial Int. 2006; 26: 697-704PubMed Google Scholar, 15Wang A.Y. Sea M.M. Tang N. et al.Resting energy expenditure and subsequent mortality risk in peritoneal dialysis patients.J Am Soc Nephrol. 2004; 15: 3134-3143Crossref PubMed Scopus (102) Google Scholar but this underestimates total energy expenditure (TEE), by excluding that due to activity energy expenditure. We recently validated an assessment of TEE and REE in dialysis patients using a patient self-reported questionnaire and doubly labeled isotopic water.16Sridharan S. Wong J. Vilar E. Farrington K. Comparison of energy estimates in chronic kidney disease using doubly-labelled water.J Hum Nutr Diet. 2016; 29: 59-66Crossref PubMed Scopus (14) Google Scholar, 17Vilar E. Machado A. Garrett A. et al.Disease-specific predictive formulas for energy expenditure in the dialysis population.J Ren Nutr. 2016; 29: 59-66Google Scholar To establish whether there is a difference in the amount of dialysis delivered for a 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. We studied 148 adult PD patients with a mean calculated REE of 1534 ± 241 kcal/d and TEE 1974 ± 414 kcal/d (Table 1). Twenty-five percent were classified as high comorbidity18Sridharan S. Berdeprado J. Vilar E. et al.A self-report comorbidity questionnaire for haemodialysis patients.BMC Nephrol. 2014; 15: 134Crossref PubMed Scopus (18) Google Scholar and 48% as frail.19Rockwood K. Song X. MacKnight C. et al.A global clinical measure of fitness and frailty in elderly people.CMAJ. 2005; 173: 489-495Crossref PubMed Scopus (4316) Google Scholar Male patients were heavier than female patients and had a greater REE and TEE (Table 2). Patients who were employed, those with greater weight, and greater protein nitrogen appearance (PNA) had a higher TEE (Table 2), whereas those with greater frailty and comorbidity, those who were diabetic, and those who were Asian tended to have a lower TEE.Table 1Patient demographic characteristics, peritoneal dialysis prescription, results of peritoneal dialysis adequacy, and transport status in all patients and those with contemporaneous bioimpedance measurementsVariableTotal CohortBioimpedance GroupN148118Male, %65.563.6Age, yr60.6 ± 17.559.5 ± 18.2Weight, kg73.6 ± 16.773.1 ± 16.6Body surface area, m21.86 ± 0.241.85 ± 0.24White43.242.4African/Afro-Caribbean24.321.1South Asian27.729.7East Asian5.46.8Employed20.322.9Dialysis vintage, mo9.1 (3.5–25.2)9.4 (3.8–25.5)Comorbidity score4.0 (0–6.0)4.0 (0–6.0)Heart disease, %19.719.7Myocardial infarction, %10.29.4Diabetes mellitus, %32.429.7Frailty3.0 (3.0–4.0)3.0 (3.0–4.0)Hemoglobin, g/l109.9 ± 4.8110.5 ± 4.5Serum albumin, g/l36.5 ± 5.536.6 ± 5.6C-reactive protein, mg/l5.0 (2.0–16.8)5.0 (2.0–15.0)Serum glucose, mmol/l5.9 (4.9–8.5)5.7 (4.9–5.1)IFCC, mmol/mg38.4 (33.3–51.4)36.2 (32.7–47.5)Serum cholesterol, mmol/l4.47 ± 1.444.50 ± 1.50Serum urea, mmol/l18.4 ± 6.118.5 ± 5.9Serum creatinine, μmol/l698 (523–871)696 (525–909)Peritoneal cycler, %85.583.9Icodextrin use, %75.781.2Icodextrin volume, l/d1.8 (0.5–2.0)1.8 (1.0–2.0)22.7–23.0 glucose use, %57.454.222.7–23.0 glucose, l/d2.5 (0–5.0)2.9 (0–6)Previous peritonitis episodes0 (0–1)0 (0–1)Total weekly Kt/Vurea2.1 (1.7–2.6)2.1 (1.7–2.60)Weekly urinary Kt/Vurea0.8 (0.3–1.3)0.9 (0.3–1.4)Weekly peritoneal Kt/Vurea1.2 (0.9–1.6)1.2 (0.8–1.6)Total creatinine cleared per week/1.73 m267.4 (55.8–84.7)70.1 (55.8–86.7)Urine creatinine cleared per week/1.73 m2, L29.6 (13.4–58.4)28.9 (12.7–59.4)Peritoneal creatinine cleared per week/1.73 m2, L35.6 (23.2–45.2)37.3 (23.5–49.3)Urine <100 ml/d, %12.215.3Urine volume, ml/d946 (450–1249)940 (448–1408)4-hr dialysate/plasma creatinine0.71 ± 0.110.73 ± 0.1124-hr ultrafiltrate, ml566 (200–908)536 (192–899)Protein nitrogen appearance, g/kg per day0.89 ± 0.260.89 ± 0.25IFCC = International Federation of Clinical Chemists.Values shown as number, mean ± SD, median (interquartile range), and percentage. Open table in a new tab Table 2Estimates of daily REE and TEE in patients according to age, comorbidity, frailty, and ethnicity groupingsVariableREE, kcal/dTEE, kcal/dMale1597 ± 2172029 ± 423Female1412 ± 2401P < 0.01 comparing groups, adjusted for multiple comparisons (Bonferroni method).1868 ± 3772P < 0.05, adjusted for multiple comparisons (Bonferroni method).Age 65 yr1408 ± 2111P < 0.01 comparing groups, adjusted for multiple comparisons (Bonferroni method).1750 ± 3141P < 0.01 comparing groups, adjusted for multiple comparisons (Bonferroni method).Nondiabetic1522 ± 2332021 ± 435Diabetic1556 ± 2541893 ± 3662P < 0.05, adjusted for multiple comparisons (Bonferroni method).Employed1577 ± 2372305 ± 511Unemployed1523 ± 2421890 ± 3401P < 0.01 comparing groups, adjusted for multiple comparisons (Bonferroni method).Low comorbidity1532 ± 2452012 ± 441High comorbidity1539 ± 2311862 ± 300Low frailty score1533 ± 2272049 ± 453High frailty score1535 ± 2561894 ± 3532P < 0.05, adjusted for multiple comparisons (Bonferroni method).Weight <64 kg1305 ± 1511706 ± 306Weight 64–80 kg1514 ± 1421P < 0.01 comparing groups, adjusted for multiple comparisons (Bonferroni method).1973 ± 4141P < 0.01 comparing groups, adjusted for multiple comparisons (Bonferroni method).Weight >80 kg1775 ± 1591P < 0.01 comparing groups, adjusted for multiple comparisons (Bonferroni method).2233 ± 3391P < 0.01 comparing groups, adjusted for multiple comparisons (Bonferroni method).PNA 60 g/d1622 ± 2291P < 0.01 comparing groups, adjusted for multiple comparisons (Bonferroni method).2133 ± 4381P < 0.01 comparing groups, adjusted for multiple comparisons (Bonferroni method).Non-Asian1561 ± 2252060 ± 462Asian1522 ± 2431866 ± 3592P < 0.05, adjusted for multiple comparisons (Bonferroni method).REE, energy expenditure; TEE, total energy expenditure; PNA, protein nitrogen appearance.Daily PNA g/d. Results expressed as mean ± SD.1 P < 0.01 comparing groups, adjusted for multiple comparisons (Bonferroni method).2 P < 0.05, adjusted for multiple comparisons (Bonferroni method). Open table in a new tab IFCC = International Federation of Clinical Chemists. Values shown as number, mean ± SD, median (interquartile range), and percentage. REE, energy expenditure; TEE, total energy expenditure; PNA, protein nitrogen appearance. Daily PNA g/d. Results expressed as mean ± SD. As previous studies have suggested that Kt be adjusted for body surface area (BSA), we compared Watson TBW with BSA. Although there was a strong association between TBW and BSA (r2 = 0.99, P < 0.001 for women and r2 = 0.83, P < 0.001 for men), BSA was relatively greater at lower TBW volumes and relatively lower at higher TBW volumes. TBW had also measured by bioimpedance at the time of adequacy testing in 118 of the patients (79.7%) (Table 1). There was no statistically significant difference in TBW: Watson equation, 40.3 ± 6.1 versus bioimpedance, 40.6 ± 3.4 L; mean difference on Bland-Altman analysis, 0.72 L (Figure 1). Although the mean difference for women was 1.43 L and that for men was 0.31 L, the 95% limits of agreement were broad; −9.20 to 10.16 L for women, and from −11.04 to 11.66 L for men. There were positive correlations between BSA and both REE and TEE (r = 0.92, P < 0.001 and r = 0.59, P < 0.001, respectively) and also between TBW and both REE and TEE (r = 0.85, P < 0.001 and r = 0.66, P < 0.001, respectively). Clinical guidelines have recommended a minimal weekly Kt/Vurea of 1.7. We then calculated Kt values for a weekly Kt/Vurea of 1.7 using both Watson equation and bioimpedance estimates of TBW. These Kt values were then adjusted by BSA, REE, and TEE. There was a positive relationship between TBW and Kt/TEE (Figure 2). The results of the adjusted Kt dialysis dosing are shown in Table 3 and Figure 3 for different patient groups. For the same prescribed dialysis dose (Kturea), women, younger patients, patients who were employed, and patients weighing less (Figure 3) received less dialysis than men, older patients, unemployed patients, and heavier patients (Table 3). In addition, patients with fewer comorbidities and less frailty, nondiabetic patients, and patients of non-Asian races also tended to receive less dialysis than those with more comorbidities and those who were diabetic, frail, and of Asian ethnicity.Table 3Comparison 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)VariableKt/BSAKt/REEWKt/TEEWKt/REEBIAKt/TEEBIAMale5.13 ± 0.366.15 ± 9.614.96 ± 0.716.23 ± 0.624.93 ± 0.70Female4.42 ± 0.401P < 0.01 after Bonferroni post hoc correction for multiple testing.5.50 ± 0.411P < 0.01 after Bonferroni post hoc correction for multiple testing.4.23 ± 0.651P < 0.01 after Bonferroni post hoc correction for multiple testing.5.64 ± 0.641P < 0.01 after Bonferroni post hoc correction for multiple testing.4.27 ± 0.711P < 0.01 after Bonferroni post hoc correction for multiple testing.Age 65 yr4.95 ± 0.426.38 ± 0.491P < 0.01 after Bonferroni post hoc correction for multiple testing.5.18 ± 0.611P < 0.01 after Bonferroni post hoc correction for multiple testing.6.12 ± 0.624.93 ± 0.651P < 0.01 after Bonferroni post hoc correction for multiple testing.Diabetic4.96 ± 0.456.03 ± 0.585.00 ± 0.691P < 0.01 after Bonferroni post hoc correction for multiple testing.5.92 ± 0.654.93 ± 0.692P < 0.05 after Bonferroni post hoc correction for multiple testing.Nondiabetic4.84 ± 0.465.90 ± 0.664.53 ± 0.826.06 ± 0.714.57 ± 0.78High frailty4.91 ± 0.476.06 ± 0.664.96 ± 0.756.01 ± 0.614.90 ± 0.71Low frailty4.86 ± 0.435.85 ± 0.602P < 0.05 after Bonferroni post hoc correction for multiple testing.4.46 ± 0.781P < 0.01 after Bonferroni post hoc correction for multiple testing.6.01 ± 0.754.54 ± 0.781P < 0.01 after Bonferroni post hoc correction for multiple testing.High comorbidity4.99 ± 0.436.19 ± 0.635.14 ± 0.665.91 ± 0.634.90 ± 0.63Low comorbidity4.85 ± 0.455.87 ± 0.621P < 0.01 after Bonferroni post hoc correction for multiple testing.4.55 ± 0.801P < 0.01 after Bonferroni post hoc correction for multiple testing.6.05 ± 0.714.62 ± 0.81Unemployed4.89 ± 0.435.99 ± 0.614.87 ± 0.725.96 ± 0.734.81 ± 0.75Employed4.89 ± 0.545.82 ± 0.714.07 ± 0.821P < 0.01 after Bonferroni post hoc correction for multiple testing.6.19 ± 0.514.31 ± 0.721P < 0.01 after Bonferroni post hoc correction for multiple testing.High PNA rate4.79 ± 0.405.91 ± 0.624.75 ± 0.785.77 ± 0.704.56 ± 0.70Low PNA rate4.95 ± 0.482P < 0.05 after Bonferroni post hoc correction for multiple testing.5.98 ± 0.684.62 ± 0.876.23 ± 0.592P < 0.05 after Bonferroni post hoc correction for multiple testing.4.81 ± 0.81Asian4.87 ± 0.465.97 ± 0.654.67 ± 0.856.10 ± 0.654.71 ± 0.76Other4.87 ± 0.425.90 ± 0.604.79 ± 0.695.79 ± 0.762P < 0.05 after Bonferroni post hoc correction for multiple testing.4.64 ± 0.80BIA, 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. Open table in a new tab Figure 3Adjusted daily urea clearance according to body weight. Fixed weekly Kt of 1.7 urea adjusted for body surface area (BSA) and resting energy expenditure (REE) and total energy expenditure (TEE) using Watson (W) total body water or bioimpedance (BIA) measured total body water. *P < 0.05 and **P < 0.01 versus weight <64 kg after Bonferroni correction.View Large Image Figure ViewerDownload (PPT) 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. Multivariable analysis showed that sex was a significant predictor of Kt/BSA (Table 4). Sex and age were significant predictors of Kt/REE. For Kt/TEE, sex, age, and employment were common predictive factors irrespective of whether Kt was derived using TBW calculated by the Watson equation or bioimpedance. Both high comorbidity and diabetes were additional predictive factors for TEE, adjusted using the Watson formula for TBW (Table 4).Table 4Multivariable step backward models for weekly Kt adjusted for BSA, REE, TEE using both total body water calculated by Watson equation and measured by BIA, unstandardized β, SE, standardized β, and 95% CLVariableβSE βStandardized βt95% CLP ValueKturea/BSA Male0.700.050.7713.50.6, 0.87<0.001Kturea/REEW Male0.580.080.447.50.43, 0.74<0.001 Age, yr0.020.010.549.30.2, 0.25<0.001Kturea/REEBIA PNA rate0.010.010.374.40.01, 0.02<0.001 Male0.390.120.283.20.15, 0.630.002 Age, yr0.010.010.192.30.01, 0.010.025Kturea/TEEW Male0.590.100.356.10.40, 0.79<0.001 Age, yr0.020.010.447.50.02, 0.013<0.001 Unemployed0.520.110.264.50.29, 0.74<0.001 High comorbidity0.300.110.162.70.01, 0.520.009 Diabetic0.210.100.122.00.01, 0.410.045Kturea/TEEBIA Male0.510.130.333.80.25, 0.77<0.001 Age, yr0.010.010.327.50.01, 0.02 35; in our study group, <2% had a body mass index of this level. We then adjusted the delivered dialysis dose by both BSA, which is relatively greater for patients with lower TBW and relatively lower for those with greater TBW and also for both REE and TEE. Adjusting Kt for BSA, which has been advocated for hemodialysis patients,23Ramirez S.P. Kapke A. Port F.K. et al.Dialysis dose scaled to body surface area and size-adjusted, sex-specific patient mortality.Clin J Am Soc Nephrol. 2012; 7: 1977-1987Crossref PubMed Scopus (47) Google Scholar we found that this resulted in a lower dose being delivered to women and those with a high PNA rate and lower body weight. Adjusting for REE, female sex, younger age, lower weight, lower PNA along with frailty and comorbidity scores, and ethnicities other than Asian, all received relatively less delivered dialysis. When Kt was adjusted for TEE, then women, younger patients, and those weighing less, those who were employed, and those with less frailty, in particular those without diabetes, all would receive lower delivered dialysis dosing compared with men, heavier patients, those unemployed, those more frail, comorbid patients, and those with diabetes. Previous studies targeting a dialysis dose defined by a weekly KtVurea for PD patients have not shown an advantage of 1 target compared with another.3Paniagua R. Amato D. Vonesh E. et al.Mexican Nephrology Collaborative Study GroupEffects of increased peritoneal clearances on mortality rates in peritoneal dialysis: ADEMEX, a prospective, randomized, controlled trial.J Am Soc Nephrol. 2002; 13: 1307-1320Crossref PubMed Scopus (1576) Google Scholar, 4Lo W.K. Ho Y.W. Li C.S. et al.Effect of Kt/V on survival and clinical outcome in CAPD patients in a randomized prospective study.Kidney Int. 2003; 64: 649-656Abstract Full Text Full Text PDF PubMed Scopus (217) Google Scholar Our study shows that achieving the same urea clearance does not equate to the same delivered dose of dialysis and, as such, potentially explains why prospective studies have failed to show a significant benefit of 1 KtVurea target for all patients. There are a number of limitations that should be considered. We used solely a weekly target Kt/Vurea, whereas some guidelines additionally recommend liters of creatinine cleared as an additional target for PD patients, and there may be differences between these targets depending on use of PD cyclers, and the amount of residual renal function.1Woodrow G, Davies SJ. Peritoneal Dialysis (PD) (Guidelines PD 3.1 – 3.3). Available at: http://www.renal.org/guidelines/modules/peritoneal-dialysis-in-ckd#sthash.Br67xjah.dpuf. Accessed July 25, 2016.Google Scholar, 24Dombros N. Dratwa M. Feriani M. et al.EBPG Expert Group on Peritoneal DialysisEuropean best practice guidelines for peritoneal dialysis. 7 Adequacy of peritoneal dialysis.Nephrol Dial Transplant. 2005; 20: ix21-ix23PubMed Google Scholar We adjusted Kt using both the Watson equation and bioimpedance. There were some differences between these methods. The Watson equation was established using a healthy population, whereas PD patients have increased TBW.25Papakrivopoulou E. Booth J. Pinney J. Davenport A. Comparison of volume status in asymptomatic haemodialysis and peritoneal dialysis outpatients.Nephron Extra. 2012; 2: 48-54PubMed Google Scholar As such, bioimpedance measurements are preferable, but ideally should be measured with the peritoneal dialysate drained.26Fan S. Sayed R.H. Davenport A. Extracellular volume expansion in peritoneal dialysis patients.Int J Artif Organs. 2012; 35: 338-345Crossref PubMed Scopus (46) Google Scholar In addition, we calculated PNA rates using equations developed in a previous era, when patients were predominantly treated by continuous ambulatory PD and glucose-only dialysates,27Bergström J. Heimbürger O. Lindholm B. Calculation of the protein equivalent of total nitrogen appearance from urea appearance. Which formulas should be used?.Perit Dial Int. 1998; 18: 467-473Crossref PubMed Scopus (157) Google Scholar and although these are often used as a surrogate for dietary protein intake, these estimates may not be as reliable for patients with increasing comorbidity, and we did not formally estimate dietary protein intake. Although we accepted that using Kt/Vurea for dialysis dosing has some limitations,28Davenport A. Effect of intra-abdominal dialysate on bioimpedance-derived fluid volume status and body composition measurements in peritoneal dialysis patients.Perit Dial Int. 2013; 33: 578-579Crossref PubMed Scopus (25) Google Scholar more recent observational studies have suggested an advantage for adjusting Kt for BSA.23Ramirez S.P. Kapke A. Port F.K. et al.Dialysis dose scaled to body surface area and size-adjusted, sex-specific patient mortality.Clin J Am Soc Nephrol. 2012; 7: 1977-1987Crossref PubMed Scopus (47) Google Scholar We found that adjusting for BSA detected a difference between men and women and in relation to body weight and PNA. However, adjusting for TEE additionally demonstrated that younger and more fit patients, employed patients, and patients with less comorbidity received a relatively lower delivered dialysis dose compared with older, more frail, comorbid, and diabetic patients. Although we chose to investigate the effect of a weekly target Kt/Vurea of 1.7, our findings would be equally applicable to any set Kt/V target applied to patients. Therefore, we suggest 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. Adult patients with end-stage kidney disease established on PD were recruited from University College London partner hospitals when attending for outpatient assessments of PD adequacy. Corresponding spent dialysate effluent, 24-hour urine collections, and serum samples were analyzed by standard methods, and the weekly dialysis dose was calculated as Kt/Vurea. The PNA rate was estimated using the Bergström equation and normalized for body weight (g/kg per day).27Bergström J. Heimbürger O. Lindholm B. Calculation of the protein equivalent of total nitrogen appearance from urea appearance. Which formulas should be used?.Perit Dial Int. 1998; 18: 467-473Crossref PubMed Scopus (157) Google Scholar Patient demographic characteristics were obtained from computerized hospital records, and comorbidity was determined using self-administered comorbidity grading18Sridharan S. Berdeprado J. Vilar E. et al.A self-report comorbidity questionnaire for haemodialysis patients.BMC Nephrol. 2014; 15: 134Crossref PubMed Scopus (18) Google Scholar based on medical conditions and complications including diabetes mellitus (as defined by WHO criteria), cardiac disease, respiratory disease, liver disease, arthritis, depression, malignancy, and a frailty score previously reported in patients with chronic kidney disease.19Rockwood K. Song X. MacKnight C. et al.A global clinical measure of fitness and frailty in elderly people.CMAJ. 2005; 173: 489-495Crossref PubMed Scopus (4316) Google Scholar We defined a high comorbidity score as ≥4.0 and a high frailty score ≥4.0, in keeping with previous studies.18Sridharan S. Berdeprado J. Vilar E. et al.A self-report comorbidity questionnaire for haemodialysis patients.BMC Nephrol. 2014; 15: 134Crossref PubMed Scopus (18) Google Scholar, 19Rockwood K. Song X. MacKnight C. et al.A global clinical measure of fitness and frailty in elderly people.CMAJ. 2005; 173: 489-495Crossref PubMed Scopus (4316) Google Scholar TBW was calculated using the Watson equation.8Watson P.E. Watson I.D. Batt R.D. Total body water volume for adult males and females estimated from simple anthropometric measurements.Am J Clin Nutr. 1980; 33: 27-39Crossref PubMed Google Scholar In addition, in 118 of the patients, contemporaneous measurements of TBW made with bioimpedance (InBody 720, InBody, Seoul, South Korea; Body Composition Monitor, Fresenius, Bad Homberg, Germany), which had been performed in a standardized manner,28Davenport A. Effect of intra-abdominal dialysate on bioimpedance-derived fluid volume status and body composition measurements in peritoneal dialysis patients.Perit Dial Int. 2013; 33: 578-579Crossref PubMed Scopus (25) Google Scholar, 29Fürstenberg A. Davenport A. Assessment of body composition in peritoneal dialysis patients using bioelectrical impedance and dual-energy x-ray absorptiometry.Am J Nephrol. 2011; 33: 150-156Crossref PubMed Scopus (110) Google Scholar were available for review. Bioimpedance measurements made by the Body Composition Monitor and InBody were standardized using previously derived equations.30McCafferty K. Fan S. Davenport A. Extracellular volume expansion, measured by multi-frequency bioimpedance, does not help preserve residual renal function in peritoneal dialysis patients.Kidney Int. 2014; 85: 151-1557Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar BSA was calculated using the Gehan and George equation, as recommended by the European Best Clinical Practice guidelines.24Dombros N. Dratwa M. Feriani M. et al.EBPG Expert Group on Peritoneal DialysisEuropean best practice guidelines for peritoneal dialysis. 7 Adequacy of peritoneal dialysis.Nephrol Dial Transplant. 2005; 20: ix21-ix23PubMed Google Scholar Physical activity data were obtained using the Recent Physical Activity Questionnaire,16Sridharan S. Wong J. Vilar E. Farrington K. Comparison of energy estimates in chronic kidney disease using doubly-labelled water.J Hum Nutr Diet. 2016; 29: 59-66Crossref PubMed Scopus (14) Google Scholar which collects information about both activity and the time spent performing activities over the preceding 4 weeks, including activities performed at home and work and during leisure time. The Recent Physical Activity Questionnaire has been validated against a doubly labeled water technique in the general population and has been shown to be a reliable tool for estimation of energy expenditure in patients with chronic kidney disease.16Sridharan S. Wong J. Vilar E. Farrington K. Comparison of energy estimates in chronic kidney disease using doubly-labelled water.J Hum Nutr Diet. 2016; 29: 59-66Crossref PubMed Scopus (14) Google Scholar Physical activity data were determined by each reported activity being assigned a metabolic equivalent of task (MET) value according to the Compendium of Physical Activities.31Ainsworth B.E. Haskell W.L. Herrmann S.D. et al.2011 Compendium of Physical Activities: a second update of codes and MET values.Med Sci Sports Exerc. 2011; 43: 1575-1581Crossref PubMed Scopus (3793) Google Scholar The equations for calculating REE and TEE are detailed in the Supplementary Appendix. UK clinical guidelines recommend a minimum weekly Kt/Vurea of 1.7.1Woodrow G, Davies SJ. Peritoneal Dialysis (PD) (Guidelines PD 3.1 – 3.3). Available at: http://www.renal.org/guidelines/modules/peritoneal-dialysis-in-ckd#sthash.Br67xjah.dpuf. Accessed July 25, 2016.Google Scholar, 32Daugirdas J.T. Kt/V (and especially its modifications) remains a useful measure of haemodialysis dose.Kidney Int. 2015; 88: 466-473Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar Hence, in order to compare minimum dialysis targets using alternative scaling parameters, weekly Kt was calculated as Kt = 1.7 multiplied by V. Corresponding target values of Kt/BSA, Kt/REE, and Kt/TEE were calculated by dividing daily Kt by the respective parameters. Ethical approval of the study was granted by the UK National Research Ethics Committee–Essex, and the study was registered in UK Clinical Research Network portfolio number 14018. All patients provided written informed consent in keeping with the Declaration of Helsinki. Statistical analysis was performed using the Student t test or Mann-Whitney U test, analysis of variance, the Kruskal-Wallis test with appropriate post hoc correction, the Pearson or Spearman test for univariate correlation (GraphPad Prism, version 6.0, San Diego, CA), and step backward linear regression of variables on univariate analysis of P < 0.1 and those considered to be clinically relevant, with log transformation of variables that were not normally distributed and removal of variables that were not statistically significant unless they improved model fit. Models were checked for collinearity using SPSS, version 22 (SPSS Inc., Chicago, IL) and the Bland-Altman comparison (Analyse-It Software, version 3.0, Leeds, UK). Data are presented as the mean ± SD, median (interquartile range), mean and 95% confidence limits (CL), or percentage. All the authors declared no competing interests. The study was funded by a grant from the British Renal Society. SE-K was awarded an International Society for Nephrology fellowship. Download .docx (.02 MB) Help with docx files Supplementary AppendixResting energy expenditure (REE) was estimated from a newer novel predictive equation that was derived and validated in a cohort of hemodialysis patients.18Sridharan S. Berdeprado J. Vilar E. et al.A self-report comorbidity questionnaire for haemodialysis patients.BMC Nephrol. 2014; 15: 134Crossref PubMed Scopus (18) Google Scholar Normalizing the peritoneal dialysis dose—have we got it right?Kidney InternationalVol. 90Issue 6PreviewHow the dialysis dose is normalized is just one of several assumptions that clinicians need to take into account when prescribing peritoneal dialysis. El-Kateb et al. confirm that estimating the volume of urea distribution is associated with significant error and show that energy expenditure is not linearly related to volume, such that there is a potential need for a higher dialysis prescription in smaller, more active individuals. Full-Text PDF Open Archive
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