PART FOUR Metaolism and Nutrition
Advances in Peritoneal Dialysis, Vol. 19, 2003 Antonios H. Tzamaloukas, 1 Glen H. Murata, 2 Dorothy J. Vanderjagt, 3 Karen S. Servilla, 1 Roert H. Glew 3 Normalization of Protein Nitrogen Appearance y Various Size Indicators in Patients on Continuous Peritoneal Dialysis Protein nitrogen appearance (PNA) estimated from urea nitrogen appearance (UNA) reflects dietary protein intake and is an important index of nutrition in peritoneal dialysis (PD). Normalization of PNA y several ody size indicators has resulted in discrepancies etween normalized PNA () values and other nutrition indices in PD patients with varying weight status. To test whether a particular size indicator produces values that eliminate the discrepancies, we normalized PNA values otained at the first clearance study in 925 PD patients y weight (W), y fat-free mass (FFM) otained from ody water, y lean ody mass (LBM) derived from creatinine kinetics, y desirale weight (DW), y standard weight (SW), and y adjusted edema-fee ody weight (abw). We classified patients into three groups according to W/DW: an underweight group [group I: W/DW < 0.9, n = 147 (15.9%)], a normal-weight group [group II: 0.9 W/DW < 1.2, n = 506 (54.7%)], and an oese group [group III: W/DW 1.2, n = 272 (29.4%)]. The UNA and PNA increased progressively from group I to group III. The W, FFM, LBM, SW, and abw also increased progressively, and the corresponding values decreased progressively from group I to group III all at p < 0.001. The DW did not differ significantly etween the three groups. The PNA values normalized y DW were 0.91 ± 0.21 (group I), 0.96 ± 0.24 (group II), and 1.07 ± 0.25 (group III), p < 0.001. Of the six size indicators tested, only DW produced values of From: 1 Renal Section and 2 General Internal Medicine Section, New Mexico Veterans Affairs Health Care System, and Department of Medicine, University of New Mexico School of Medicine; and 3 Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Aluquerque, New Mexico, U.S.A. consistent with the nutrition status of PD patients with varying weight status. Our findings indicate that DW is the proper size indicator for normalizing PNA in PD patients. Key words Protein nitrogen appearance, actual ody weight, fatfree mass, lean ody mass, desirale weight, standard weight, adjusted edema-free ody weight Introduction Nutrition affects the outcome of peritoneal dialysis (PD). Consequently, monitoring the nutrition status of PD patients is recommended (1,2). Protein nitrogen appearance (PNA), estimated from urea nitrogen excretion in urine plus dialysate, is a useful index of nutrition in PD (1,2). The PNA is routinely normalized () y a size indicator to allow for comparisons etween sujects of varying ody size. However, discrepancies have een reported etween values and other indices of nutrition in PD patients with varying weight status. Normalization of PNA y actual weight (W) or standard weight (SW: V/0.58, where V is ody water) produces relatively low values in oese PD patients, who tend to have good nutrition indices, and relatively high values in underweight PD patients, who routinely have poor nutrition indices (3 5). The question aout normalization of PNA that remains unanswered to date is whether a particular size indicator produces values that reflect, without systematic errors, the nutrition status of PD patients with varying weight status. Several studies have simultaneously used multiple size indicators for such a purpose (4 6). Furthermore, current guidelines offer conflicting instructions aout the size indicator that should properly e used to normalize PNA. The guide-
208 lines on adequacy of nutrition in renal failure patients (1) recommend use of adjusted-edema free ody weight (abw), ut the guidelines for adequacy of PD (2) suggest the use of oth standard weight (SW) and lean ody mass (LBM) estimates derived from creatinine kinetics. The present study tested whether any particular size indicator might produce values consistent with the prevailing nutritional characteristics of oese, normal-weight, and underweight PD patients. To properly descrie the differences, the values should increase progressively from the underweight patients to the patients in the oese group. Patients and methods We analyzed PNA values for 925 North American patients at the time of their first clearance study, which was performed 7.1 ± 6.5 months after initiation of PD. The dialysis units following the patients, the characteristics of the patients and their PD schedules, and the details of the clearance methods have een descried elsewhere (4,5,7 10). In calculating clearances and nutrition indices derived from urea nitrogen appearance, we made these modifications: Body water (V) was estimated using the Sahlgrenska formulas (11). We elected to use those formulas ecause they are the only ones that were derived in PD patients. Estimates of V y the Sahlgrenska formulas and the Watson formulas agree closely (11,12). The PNA was computed y the Bergström formula (13), ecause that formula was derived in PD patients and is recommended y current guidelines (2). The Bergström formula is PNA = 20.1 + 7.50 UNA, [1] where UNA (urea nitrogen appearance in urine plus dialysate) and PNA are expressed as grams in a 24-hour period. The PNA was then normalized to these size indicators: actual ody weight ( W ), fat-free mass ( FFM ), lean ody mass ( LBM ), desirale weight ( DW ), standard weight ( SW ), and adjusted edema-free ody weight ( abw ). The FFM was calculated as V/0.73 (12). The LBM was Tzamaloukas et al. otained from creatinine kinetics (14,15). The DW was otained from the Metropolitan Life Insurance tales (16), assuming medium skeletal frame. The SW was calculated as V/0.58 (7), and the abw was otained y using this formula (17): abw = BW ef + [ (NW BW ef ) 0.25 ], [2] where BW ef is a clinical estimate of edema-free ody weight, and NW is the normal ody weight (2,17). In a previous study, we estimated that edema represents, on average, 3% of actual ody weight in PD patients (18). The BW ef was therefore estimated as 0.97 W. Calculation of NW requires elow-readth measurement (17), which was unavailale in the present study. We therefore estimated NW according to this formula (17,19): NW = 1.09 DW. [3] Patients were classified into one of three weight categories ased on the ratio of their actual weight (W) to their desirale weight (DW). Patients whose W/DW was 0.9 were classified as underweight; those with 0.9 < W/DW 1.2 were classified as normal-weight; and those with W/DW > 1.2 were classified as oese (20). Continuous variales were first compared etween underweight, normal-weight, and oese patients y one-way analysis of variance (one-way ANOVA), which requires equal variances for all the groups tested. However, for some parameters, the Bartlett test showed lack of homogeneity of group variances. Therefore, the comparisons of continuous variales were repeated using a nonparametric statistical method namely, the Kruskal Wallis one-way ANOVA. Differences etween the one-way ANOVA and the Kruskal Wallis statistic are noted in the text. Categorical variales were compared y chi-square test. Results Tale I summarizes the characteristics of the PD patients y their classifications as underweight, normalweight, and oese. The normal-weight group contained relatively fewer women than either the underweight or the oese group. The percentage of patients with diaetes mellitus increased progressively from the underweight group to the oese group. The
Normalized PNA in PD 209 TABLE I Summary of the characteristics of the three weight groups of peritoneal dialysis (PD) patients a Group I Group II Group III Underweight Normal-weight Oese p Value Patients [n (%)] 147 (15.9%) 506 (54.7%) 272 (29.4%) Sex Male 75 (51.0%) 336 (66.4%) 141 (51.8%) Female 72 (49.0%) 170 (33.6%) 131 (48.2%) <0.001 Diaetes Yes 49 (33.3%) 206 (40.7%) 143 (52.6%) No 98 (66.7%) 300 (59.3%) 129 (47.4%) 0.017 Age (years) 45.7±18.0 55.6±14.5 55.6±12.7 <0.001 PD duration (months) 7.1±4.2 7.1±3.1 6.9±3.2 NS BMI (kg/m 2 ) 18.8±1.6 24.3±2.0 31.8±3.9 <0.001 W/DW 0.81±0.07 1.05±0.08 1.38±0.17 <0.001 Kt/V urea 2.22±0.56 2.02±0.57 2.02±0.55 0.001 CCr (L/1.73 m 2 ) 72.2±27.9 68.9±26.7 69.2±27.5 NS a The p values in the comparisons of continuous variales in this tale were otained y one-way ANOVA. The Kruskal Wallis statistic produced the same p values for all comparisons except Kt/V urea (Kruskal Wallis statistic: p < 0.001). Weekly values. NS = nonsignificant; BMI = ody mass index; W = actual weight; DW = desirale weight; CCr = creatinine clearance. underweight group was younger and had higher normalized urea clearances than either the normal-weight group or the oese group. Tale II shows the PNA and values and their determinants. The UNA, PNA, W, FFM ased on the Sahlgrenska formula, LBM derived from creatinine kinetics, SW, and abw all increased progressively from the underweight group to the oese group. The DW did not differ etween the three weight groups. Despite the increase in PNA values from the underweight group to the oese group, the corresponding values of PNA normalized y W, FFM, LBM, SW, and abw progressively decreased. In contrast, PNA normalized y DW increased progressively from the underweight group to the oese group. Other relevant values Blood urea nitrogen (BUN) was 51.1 ± 16.2 mg/dl in the underweight group, 55.6 ± 14.5 mg/dl in the normal-weight group, and 55.1 ± 18.0 mg/dl in the oese group (one-way ANOVA: p = 0.036; Kruskal Wallis statistic: p = 0.083). Serum creatinine was 8.6 ± 3.0 mg/dl in the underweight group, 9.9 ± 3.7 mg/dl in the normal-weight group, and 9.9 ± 3.4 mg/dl in the oese group (one-way ANOVA and Kruskal Wallis statistic: p < 0.001). Creatinine excretion was 784 ± 270 mg in 24 hours in the underweight group, 1002 ± 389 mg in 24 hours in the normal-weight TABLE II Comparisons a of values for urea nitrogen appearance (UNA) and protein nitrogen appearance (PNA), normalizing size indicators, and values etween the three weight groups of peritoneal dialysis (PD) patients Group I Group II Group III Underweight Normal-weight Oese p Value UNA (g/24 h) 4.7±1.7 5.6±2.1 6.3±2.3 <0.001 PNA (g/24 h) 55.3±13.0 62.4±15.9 67.6±17.6 <0.001 W (kg) 49.7±7.0 68.1±8.7 87.6±14.4 <0.001 FFM (kg) 41.1±7.0 50.2±8.4 55.9±11.6 <0.001 LBM (kg) 34.8±8.6 43.9±13.0 49.5±14.0 <0.001 DW (kg) 61.1±6.0 64.9±6.7 63.5±7.7 NS SW (kg) 51.7±8.8 63.2±10.5 70.4±14.6 <0.001 abw (kg) 52.8±6.5 67.3±7.9 81.0±12.0 <0.001 W 1.13±0.27 0.92±0.22 0.78±0.18 <0.001 FFM 1.38±0.35 1.26±0.33 1.24±0.31 <0.001 LBM 1.65±0.40 1.48±0.38 1.42±0.35 <0.001 DW 0.91±0.21 0.96±0.24 1.07±0.25 <0.001 SW 1.09±0.28 1.00±0.26 0.98±0.25 <0.001 abw 1.06±0.25 0.93±0.23 0.84±0.19 <0.001 a The p values in this tale were the same for oth the one-way ANOVA and the Kruskal Wallis statistic. g/kg in 24 hours. W = actual weight; FFN = fat-free mass; LBM = lean ody mass; DW = desirale weight; NS = nonsignificant; SW = standard weight; abw = adjusted edema-free ody weight; = normalized protein nitrogen appearance. group, and 1117 ± 405 mg in 24 hours in the oese group (one-way ANOVA and Kruskal-Wallis statistic: p < 0.001).
210 Discussion The present study aimed to provide a clear answer to the question What is the proper size indicator for normalizing PNA in PD patients? Ideally, the proper size indicator should avoid introducing systematic ias when applied to patients with varying weight status. Consequently, should reflect the oservation that oese PD patients have, in general, etter nutrition indices than patients of normal ody weight (6), and that underweight PD patients have worse nutrition indices than patients of normal ody weight (5). Our study revealed that urea nitrogen excretion [an index of protein intake (21)] and creatinine excretion [an index of somatic nutrition (22)] are highest in oese PD patients and lowest in underweight PD patients. Concomitantly, five of the six size indicators tested also increased progressively from the underweight group to the oese group (Tale II). The abw values that were used in the present study are approximations ased on DW, which underestimates normal weight y 8% 10% (17,19). However, abw in PD patients always represents an approximation, ecause it requires a clinical estimate of dry weight (7,17). The DW was the only size indicator that did not vary etween the three weight groups. Consequently, only PNA normalized y DW increased progressively from the underweight group to the oese group. All other values decreased (Tale II). Conclusion Only PNA normalized y DW reflects the differences in nutrition etween PD patients with varying weight status, and therey eliminates the systematic errors introduced y the other size indicators tested. We propose that DW is the appropriate way of expressing normalized PNA in PD patients. Acknowledgment This work was supported y the New Mexico VA Health Care System. References 1 Clinical practice guidelines for nutrition in chronic renal failure. K/DOQI, National Kidney Foundation. Am J Kidney Dis 2000; 35(Suppl 2):S1 140. 2 II. NKF-K/DOQI Clinical Practice Guidelines for Peritoneal Dialysis Adequacy: update 2000. Am J Kidney Dis 2001; 37(Suppl 1):S65 136. Tzamaloukas et al. 3 Harty JC, Boulton H, Curwell J, et al. The normalized protein cataolic rate is a flawed marker of nutrition in CAPD patients. Kidney Int 1994; 45: 103 9. 4 Tzamaloukas AH, Murata GH, Servilla KS, Hoffman RM. Weight deficit in patients on continuous amulatory peritoneal dialysis. Am J Kidney Dis 2002; 39: 1068 77. 5 Tzamaloukas AH, Murata GH, Servilla KS, Hoffman RM. Small-solute clearances and nutrition indices in oese patients on continuous peritoneal dialysis. Adv Perit Dial 2002; 18:40 3. 6 Bernardini J, Piraino B. Urea kinetics and nitrogen appearance rates in diaetic patients on peritoneal dialysis. Perit Dial Int 1995; 15:259 63. 7 Nolph KD, Moore HL, Twardowski ZJ, et al. Crosssectional assessment of weekly urea and creatinine clearances in patients on continuous amulatory peritoneal dialysis. ASAIO J 1992; 38:M139 42. 8 Tzamaloukas AH, Murata GH, Malhotra D, Fox L, Goldman RS, Avasthi PS. The minimal dose of dialysis required for a target Kt/V in continuous peritoneal dialysis. Clin Nephrol 1995; 44:316 21. 9 Tzamaloukas AH, Murata GH, Malhotra D, Fox L, Goldman RS, Avasthi PS. Creatinine clearance in continuous peritoneal dialysis: dialysis dose required for a minimal acceptale level. Perit Dial Int 1996; 16:41 7. 10 Murata GH, Tzamaloukas AH, Malhotra D, et al. Protein cataolic rate in patients on continuous peritoneal dialysis. A multivariate predictive model. ASAIO J 1996; 42:46 51. 11 Johansson AC, Samuelsson O, Attman PO, Bosæus I, Haraldsson B. Limitations in anthropometric calculations of total ody water in patients on peritoneal dialysis. J Am Soc Nephrol 2001; 12:568 73. 12 Tzamaloukas AH, Murata GH, Vanderjagt DJ, Glew RH. Estimates of ody water, fat-free mass, and ody fat in patients on peritoneal dialysis y anthropometric formulas. Kidney Int 2003; 63:1605 17. 13 Bergström J, Heimürger O, Lindholm B. Calculation of the protein equivalent of total nitrogen appearance from urea appearance. Which formulas should e used? Perit Dial Int 1998; 18:467 73. 14 Keshaviah PR, Nolph KDA, Moore HL, et al. Lean ody mass estimation y creatinine kinetics. J Am Soc Nephrol 1994; 4:1575 85. 15 Canaud B, Lelanc M, Garred LJ, Bosc JY, Argiles A, Mion C. Protein cataolic rate over lean ody mass ratio: a more rational approach to normalize the protein cataolic rate in dialysis patients. Am J Kidney Dis 1997; 30:672 9. 16 1983 Metropolitan height and weight tales. Stat Bull
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