Dialysis patients are at increased risk for muscle wasting, and time efficient screening tests are required for to allow for early detection. Creatinine kinetics have been advocated to estimate lean body mass (LBM) in peritoneal dialysis (PD) patients, and can be readily calculated in clinical practice from peritoneal dialysate effluent and urine collections. Bioimpedance is increasingly available, and we compared methods in 434 PD patients (55% men, 33.3% diabetics), mean age 55.2 ± 16.2 years. LBM was lower by creatinine kinetics (47.8 ± 16.6 kg men, 37.8 ± 11.2 kg women) vs. bioimpedance (53.2 ± 11.5 kg men, 39.2 ± 7.2 kg women), p < 0.01. The prevalence of muscle wasting was much greater using creatinine kinetics (72.4% men, 52.4% women) vs. bioimpedance (55.2% men, 37.3%), p < 0.05. Estimates of LBM were much lower using creatinine kinetics compared to bioimpedance. Studies reporting the prevalence of muscle loss in PD patients will differ depending upon the method used to estimate muscle mass

Davenport, A

Yoowannakul, S

UCL Discovery

 1Estimation of lean body mass by creatinine kinetics increases the prevalence of 1 muscle wasting in peritoneal dialysis patients compared to bioimpedance 2  3 MD, Suree Yoowannakul MD, Andrew Davenport FRCP 4   5  6 UCL Centre for Nephrology 7 Royal Free Hospital 8 University College London  9 Rowland Hill Street 10 London NW3 2PF 11 UK 12  13  14 Address for correspondence 15    16 Suree Yoowannakul   moo_yookul@hotmail.com 17 Andrew Davenport   andrewdavenport@nhs.net 18  19  20 contact andrewdavenport@nhs.net 21 UCL Centre for Nephrology, Royal Free Hospital, University College London 22 Medical School, Rowland Hill Street, London NW3 2PF 23 tel 44-2074726457 fax 44-2073178591 24  25  26  27 short title creatinine kinetics and bioimpedance   28  29  30 key words chronic kidney disease peritoneal dialysis muscle wasting 31  creatinine kinetics  bioimpedance  lean body mass 32  33  34 word count abstract 149 35   body  951 36 figures  1 37 Tables  1 38   references 10 39  40 Acknowledgements: Dr Suree Yoowannakul was awarded an International Society 41 of Nephrology training award. 42  43  44  45  2Abstract 46  47 Dialysis patients are at increased risk for muscle wasting, and time efficient 48 screening tests are required for to allow for early detection. Creatinine kinetics 49 have been advocated to estimate lean body mass (LBM) in peritoneal dialysis 50 (PD) patients, and can be readily calculated in clinical practice from peritoneal 51 dialysate effluent and urine collections. Bioimpedance is increasingly available, 52 and we compared methods in 434 PD patients (55% men, 33.3% diabetics), mean 53 age 55.2±16.2 years. LBM was lower by creatinine kinetics (47.8±16.6 kg men, 54 37.8±11.2 kg women) vs bioimpedance (53.2±11.5 kg men, 39.2±7.2 kg women), 55 p<0.01. The prevalence of muscle wasting was much greater using creatinine 56 kinetics (72.4% men, 52.4% women) vs bioimpedance (55.2% men, 37.3%), p<0.05. 57 Estimates of LBM were much lower using creatinine kinetics compared to 58 bioimpedance. Studies reporting the prevalence of muscle loss in PD patients will 59 differ depending upon the method used to estimate muscle mass. 60  61 Introduction 62 Dialysis patients are at increased risk of muscle wasting, and muscle 63 wasting is associated with increased risk for mortality. Peritoneal dialysis (PD) 64 patients have additional protein losses in the spent dialysate. For routine clinical 65 practice simple screening tests are required to detect muscle wasting 66 (sarcopenia) at an early stage to allow for intervention. Several methods have 67 been advocated for assessing lean body mass in dialysis patients and creatinine 68 kinetics is one method supported by the Kidney Disease Outcome Quality 69  3Initiative (KDOQI) clinical guidelines committee [1]. Creatinine kinetics have 70 been used to estimate lean body mass in PD patients [2]. Bioimpedance devices 71 are being increasingly used in clinical practice, and can be used to assess body 72 composition [3], and studies have reported that bioimpedance provides 73 equivalent results to dual-energy x-ray absorptiometry (DXA) in PD patients [4]. 74 As the prevalence of muscle wasting varies considerably between studies in PD 75 patients, we wished to compare the estimations of lean body mass using 76 creatinine kinetics and bioimpedance to determine whether the method used 77 changed the reported prevalence of muscle wasting. 78  79 Materials and Methods 80 Creatinine kinetics were calculated from corresponding 24-hour spent 81 peritoneal dialysate effluents, 24-hour urine collections and serum samples, 82 using standard equations [5], when patients attended for routine testing of 83 peritoneal membrane function. Enzymatic methods were used to measured 84 creatinine to exclude interference from glucose [6]. Multifrequency segmental 85 bioimpedance was performed in a standardised manner after patients had voided 86 and peritoneal dialysate drained out (InBody700, Seoul, Korea) [7]. The 87 bioimpedance machine was regularly serviced and calibrated. Muscle wasting was 88 defined by age and gender matched reference data obtained from the National 89 Health and Nutritional Survey (NHANES) [8]. 90 This retrospective audit complied with the UK National Health Service 91 (NHS) guidelines for clinical audit and service development.  92  4 93 Statistical analysis 94 Data is presented as mean ± standard deviation, median (interquartile 95 range), or as percentage. Standard statistical tests were used to analyse data. 96 using Prism 7.0 (Graph Pad, San Diego, USA) and SPSS 24 (SPSS, University of 97 Chicago, Chicago, USA) and Analyse It 4.0 (Analyse-It, Leeds, UK). Statistical 98 significance was taken as p<0.05.  99  100 Results 101 We compared lean body mass estimated by creatinine kinetics and 102 bioimpedance in 434 PD patients (table 1). Lean body mass estimated by 103 creatinine kinetics was lower for both men (47.8±16.6 kg) and women (37.8±11.2 104 kg) vs bioimpedance (53.2±11.5 kg men, 39.2±7.2 kg women), p<0.01. The mean 105 bias on Bland Altman analysis showed creatinine kinetics under-estimating lean 106 body mass compared to bioimpedance by 3.8 kg (Figure 1), with mean bias less 107 for women 1.6 kg (95% limits of agreement -18.5 to 21.8 kg), and 5.5 kg (-22.5 to 108 33.5 kg). Using NHANES reference data, the prevalence of muscle wasting was 109 72.4% for men and 52.4% for women by creatinine kinetics vs 55.2% for men 110 and 37.3% for women using bioimpedance, p<0.05. Dividing patients according to 111 ethnicity lean body mass was not statistically different (European: females 19.7 112 (14.0-27.9), males 21.3 (14.7-33.4); Asian: females 19.1 (17.0-29.8), males 21.4 113 (14.4-31.2); African Afro-Caribbean: females 19.8 (14.0-33.4), males 17.9 (12.9-114 30.9) kg, respectively.  115  5 116 Discussion 117  Studies in dialysis patients have repeatedly reported that loss of muscle 118 mass is strongly associated with an increased risk in mortality. Once established 119 protein energy wasting is difficult to reverse, and as such simple screening tests 120 are required for every day clinical practice. The routine samples obtained when 121 PD patients attend for assessment of peritoneal membrane function allow 122 estimation of lean body mass by calculating the creatinine index [5], and this 123 method has been supported by the KDOQI committee [1]. A validation study of 124 creatinine index reported similar estimates of lean body mass to those obtained 125 with DXA in PD patients, although the number of patients studied was very small 126 [2]. Bioimpedance devices are now more readily available in clinical practice, with 127 estimates of body composition in both haemodialysis and PD patients reported 128 to correlate strongly with DXA measurements [4,9]. 129 Studies reporting on the prevalence of loss of muscle mass (sarcopenia) in 130 dialysis patients have varied in results, and as such we wished to determine 131 whether some of this variance could be due to the method used to estimate 132 muscle mass. We found that creatinine kinetics under-estimated lean body mass 133 compared to that measured with bioimpedance, and the mean bias was greater 134 for men compared to women, as male dialysis patients typically have greater 135 muscle mass and are more physically active [10]. We had too few anuric patients 136 to determine whether potential differences in non-renal creatinine excretion 137 and metabolism resulted in in greater bias, compared to those with residual 138  6renal function. We did not find differences between ethnic groups, but this may 139 have been due to analysis of small numbers and differences in patient 140 demographics. Similarly we did not observe a difference with peritoneal 141 transport status. 142 When we then compared estimates of muscle mass with recognized age and 143 gender matched reference data [7], we found that the prevalence of muscle loss 144 (sarcopenia) was significantly greater when using creatinine kinetics. When 145 calculating creatinine kinetics, although urinary and peritoneal creatinine can be 146 measured by routine laboratory methods, the higher glucose concentration in 147 the spent peritoneal dialysate effluent may interfere with standard Jaffe 148 creatinine assays. To overcome this potential error, we used enzymatic methods. 149 In the steady state, estimation of lean body mass and creatinine kinetics are 150 closely correlated in healthy subjects, however in dialysis patients greater 151 amounts of creatinine are secreted into the intestine, some of which is then 152 reabsorbed, and then a variable proportion is converted back to creatine [5]. As 153 such creatinine kinetics, potentially under-estimates lean body mass in patients 154 with chronic kidney disease, and we found that the creatinine kinetics under-155 estimated lean body mass compared to bioimpedance, with the mean bias being 156 greater for male compared to female PD patients, leading to reporting a much 157 higher prevalence of muscle wasting using creatinine kinetics compared to 158 bioimpedance. Our study using bioimpedance supports previous studies which 159 compared lean body mass estimated by creatinine kinetics with that using 160 isotopic potassium [5]. We noted that there were wide limits of agreement 161  7between methods for individual patients, which may relate to variation in dietary 162 intakes and body composition.  163  Our study would suggest that creatinine kinetics is a less reliable method 164 of assessing lean body mass in PD patients and leads to an over estimation of the 165 prevalence of muscle wasting. 166 . 167   168  169 The authors have no conflict of interest 170 The data presented in this paper has not been previously published in part or 171 full form 172  173 Acknowledgements: Dr Suree Yoowannakul was awarded an International Society 174 of Nephrology training award. 175 References 176 1. Clinical practice guidelines for nutrition in chronic renal failure. K/DOQI, 177 National Kidney Foundation Am J Kidney Dis 2000; 35(6 Suppl 2):S1–140 178 2. Keshaviah PR, Nolph KD, Moore HL, Prowant B, Emerson PF, Meyer M, et 179 al. Lean body mass estimation by creatinine kinetics. J Am Soc Nephrol. 180 1994;4(7):1475-85 181 3. Kyle UG, Bosaeus I, De Lorenzo AD, Deurenberg P, Elia M, Manuel Gómez 182 J, et al; ESPEN. Bioelectrical impedance analysis-part II: utilization in 183 clinical practice. Clin Nutr. 2004;23(6):1430-53 184 4. Fürstenberg A, Davenport A. Assessment of body composition in 185 peritoneal dialysis patients using bioelectrical impedance and dual-energy 186 x-ray absorptiometry. Am J Nephrol. 2011;33(2):150-6  187 5. Dombros N, Dratwa M, Feriani M, Gokal R, Heimbürger O, Krediet R, et 188 al; EBPG Expert Group on Peritoneal Dialysis. European best practice 189 guidelines for peritoneal dialysis. 8 Nutrition in peritoneal dialysis. 190 Nephrol Dial Transplant. 2005 ;20 Suppl 9:ix28-ix33 191 6. Persaud J, Thomas M, Davenport A. Indirect ion selective electrode 192 methods potentially overestimate peritoneal dialysate sodium losses. 193 Ther Apher Dial. 2014;18(4):321-5 194 7. Davenport A. Does peritoneal dialysate affect body composition 195 assessments using multi-frequency bioimpedance in peritoneal dialysis 196 patients? Eur J Clin Nutr. 2013;67(2):223-5 197  88. Baumgartner RN, Koehler KM, Gallagher D, Romero L, Heymsfield SB, 198 Ross RR, et al. Epidemiology of sarcopenia among the elderly in New 199 Mexico. Am J Epidemiol. 1998;147(8):755-63 200 9. Fürstenberg A, Davenport A. Comparison of multifrequency bioelectrical 201 impedance analysis and dual-energy X-ray absorptiometry assessments in 202 outpatient haemodialysis patients. Am J Kidney Dis. 2010;57(1):123-129 203 10. El-Kateb S, Sridharan S, Farrington K, Fan S, Davenport A. A 204 single weekly Kt/Vurea target for peritoneal dialysis patients does not 205 provide an equal dialysis dose for all. Kidney Int. 2016 Sep 18. pii: S0085-206 2538(16)30400-8 PMID: 27653839 207  208  209  210  211  212  213  214  215  216  217  218  219  220  221  222  223  224  225  226  227  228  229  230  231  232  233  234  235  236  237  238 Figure 1: Bland Altman plot comparing lean body mass measured by 239 bioimpedance and creatinine kinetics showing mean bias and 95% limits of 240 agreement. 241  242  9 243  244  245  246  247  248  249  250  251  252  253  254  255  256 Table 1. Demographics of peritoneal dialysis patients used for estimation of lean 257 body mass by Creatinine kinetics and Bioimpedance. Peritoneal dialysis modality, 258 peritoneal membrane transport status, and urea dialysis clearance (weekly 259 Kt/Vurea), laboratory tests and multifrequency bioimpedance body composition. 260 Results shown as median (25th, 75th percentile) or number (percentage).   261  262  263  264  265  266  267  268  269  270  271  272 

Estimation of lean body mass by creatinine kinetics increases the prevalence of muscle wasting in peritoneal dialysis patients compared to bioimpedance

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Estimation of lean body mass by creatinine kinetics increases the prevalence of muscle wasting in peritoneal dialysis patients compared to bioimpedance

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