Peritoneal Dialysis International, Vol. 16, pp /96$300+00

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1 Peritoneal Dialysis International, Vol. 16, pp /96$ Printed in Canada All rights reserved Copyright 1996 International Society for Peritoneal Dialysis CONTINUOUS PERITONEAL DIAL YSIS IN HEAVYWEIGHT INDIVIDUALS: UREA AND CREATININE CLEARANCES Antonios H. Tzamaloukas,1 Athanasios Dimitriadis,2 Glen H. Murata,1 Nicoletta Nicolopoulou,3 Deepak Malhotra,1 Elias V. Balaskas,4 John Kakavas,5 Stavros Antoniou,2 Nicholas V. Dombros,4 Elleni Batzili,2 and Sonia Voudiklari5 Veterans Affairs Medical Center and University of New Mexico School of Medicine, 1 Albuquerque, New Mexico, U.S.A.,. Agios Dimitrios Hospital,2 Thessaloniki, Evaggelismos Hospital,3 Athens, "AHEPA" University Hospital,4 Thessaloniki, and Hippokrateion Hospital,5 Athens, Greece.Objective: To study whether or not continuous peritoneal dialysis (CPD) can provide acceptable levels of normalized urea and creatinine clearance in heavyweight individuals..design: Retrospective analysis of urea and creatinine clearance studies..setting: CPD patients followed in four dialysis units in Albuquerque, two dialysis units in Thessaloniki, and two dialysis units in Athens..Participants: One hundred and ninety-nine patients on CPD with 266 clearance determinations between 1991 and Interventions: The heavyweight group consisted of 22 patients (24 clearance studies) weighing 100 kg or more (109.0±8.7 kg) at the time of the clearance study. All subjects were obese. The reference group consisted of 177 CPD subjects (242 clearance studies)ofnormal weight (68.7±12.2 kg). Urea fractional clearance (KT/V) and normalized creatinine clearance (Ccr) were compared between the heavyweight and the reference groups..main Outcome Measures: The lowest acceptable weekly levels were set at 1.70 for KT/V and 54.4 L/1. 73 m2 for Ccr..Results: Weekly KT/V was 1.75±0.41 in the heavyweight group and 1.94±0.52 in the reference group (p = 0.047). Corresponding weekly Ccr levels were 64.0±24.3 and 77.6±40.3 L/1.73 m2, respectively (p = ). In the heavyweight group, 13 studies (54.2%) had acceptable KT/V values compared to 160 studies (66.1 %) in the reference group (NS). Corresponding values for acceptable Ccr were 17 (70.8%) and 165 (68.2%), respectively (NS). Drain volume was 12.96±4.40 L/24 hours in the heavyweight group and 9.63±2.58 L/24 hours in the reference group (p = ). High daily exchange volume was delivered by a combination of daily continuous ambulatory peritoneal dialysis (CAPD) and nocturnal automated peri Correspondence to: A.H. Tzamaloukas, Renal Section (111C), V A Medical Center, 2100 Ridgecrest Drive, SE, Albuquerque, New Mexico U.S.A. Received 5 September 1995; accepted 3 November toneal dialysis (APD) in heavyweight studies. This combination was tolerated better than any other method of delivering a large daily exchange volume..conclusion: Although normalized urea and creatinine clearances are lower in obese, heavyweight individuals than in lean CPD subjects with lower weight, approximately equal percentages of these two groups achieve acceptable clearance levels. However, heavyweight individuals require larger-than-usual daily exchange volumes. The preferred way to deliver these large dialysate volumes is a combination of daily CAPD and nocturnal APD. KEY WORDS: Urea clearance; creatinine clearance; obesity; body weight; body water. H eavyweight individuals on continuous peritoneal dialysis (CPD) experience difficulties achiev ing minimally acceptable levels of fractional urea clearance (KTN) (1) and creatinine clearance (Ccr) normalized to a body surface area (BSA) ofl. 73 m2 (2). The purpose of this communication was to study the circumstances under which CPD provides acceptable KTN and Ccr to heavyweight individuals. p A TIENTS AND METHODS Urea and creatinine clearance studies performed in CPD patients in eight dialysis units in Albuquerque, Thessaloniki, and Athens were analyzed. Clearance studies in heavyweight individuals (body weight exceeding loo kg) were compared to studies in a reference group. Each kinetic study was treated as an individual event. Thus, some subjects had more than one study analyzed. Clearance studies were performed by 24 hour urine and drained dialysate collections and a postcollection blood sample (3,4). Urea volume (V) was estimated by the Watson formulas (5) and BSA by the Dubois formula (2,3). Urinary Ccr was not corrected for

2 tubular excretion of creatinine (2). Protein catabolic rate (PCR) was calculated by the method of Randerson ( 6) and was normalized (PCRN) by standard weight (V/ 0.58) (3). Ideal weight was calculated by the method of Hamwi (7). Fractional deviation of weight from ideal (F Δ W) was calculated as actual weight ideal we ight)/ ideal weight (8). Subjects with FΔW < were considered malnourished, those with FΔW between and were considered normal, and those with FΔW > were considered obese (9). V, KT/ V, BSA, and Ccr were calculated at both the actual and ideal weight. Body mass index (BMI) was also calculated. Obesity, with F Δ W > (9), was present in all 24 studies of heavyweight individuals. In each case, ideal weight was much less than loo kg. Since obesity was the cause of the heavy weight in this group, the reference group consisted of all subjects who were at their normal weight. FΔW was between and in this reference group (9). The largest weight in this group was 95.4 kg. CPD subjects who were either obese, weighed <loo kg, or were malnourished were excluded from this study. Lowest acceptable weekly clearance values were setat 1. 70forKT/V(10)and54.4L/l. 73m2forCcr(2). Statistical comparison between the heavyweight group and the reference group was carried out by the twotailed Student's t- test for continuous variables and by chi-square or Fisher's Exact Test for categorical variables. Within each group, comparison between ideal and actual weight variables was carried out by the two-tailed paired t-test. RESULTS Among 440 kinetic studies performed in 302 CPD subjects, 24 studies in 22 patients (one anuric) composed the heavyweight group, and 242 studies in 177 subjects composed the reference group. Forty-two studies (30 patients) were excluded because ofmalnutrition (FΔW < -0.1), and another 132 studies (73 subjects) were excluded because of obesity (FΔW >+0.20), with weight <loo kg. Table 1 shows demographic and anthropometric variables. Although the heavyweight group was taller than the reference group by 6.8 cm, the main cause of the weight difference (40.3 kg) between the two groups was obesity. The heavyweight group was younger and contained relatively fewer diabetics than the reference group. The relative numbers of females were comparable between the two groups. Table 2 shows laboratory, clearance, and nutrition variables. Twenty-four-hour drain volume (DV) was 3.33 L higher in the heavyweight group. Sixteen patients in this group had prescribed daily exchange volume >8 L. Among these, 2 were on continuous ambulatory peritoneal dialysis (CAPD) with four daily exchanges and 3-L exchange volume, 5 were on CAPD with five to eight daily exchanges and 2-L exchange volume, and 9 were on combination daily CAPD and nocturnal automated peritoneal dialysis (APD), with a total 24-hour exchange volume as high as 22 L. Patients tolerated the last combination best. Eventually, 1 patient, initially on four daily exchanges and 3-L exchange volume, plus 3 patients, initially on more than four daily CAPD exchanges, converted to combined daily CAPDnocturnal APD. Raw urea clearance was higher in the heavyweight group, whereas KTN and Ccr were higher in the reference group (Table 2). The differences in the normalized clearances were created by higher urinary values in the reference group, while the peritoneal normalized clearances were equal between the two groups. Whereas PCR was higher in the heavyweight group, PCRN was marginally higher in the reference group. The difference in PCRN would be accentuated if PCR were normalized by the actual weight instead of the standard weight. Figure 1 compares KTN and Ccr estimates at actual and ideal weights, assuming that raw clearances are the same in the same group at the two weights. KTN and Ccr values would be higher, both at p < 0.001, at ideal than at actual weight only in the heavyweight group. In addition, while actual weight KTN was higher in the reference group (Table 2), ideal weight KTN would be higher in the heavyweight group (p = 0.022). In the heavyweight group, 13 KTN values (54.2%) were >1.70 weekly compared to 160 (66.1 %) in the reference group (NS). Corresponding values for Ccr > 54.4 L/l.73 m2 were 17 (70.8%) and 165 (68.2%), respectively (NS). Anuria was present in 10 heavyweight and 60 reference studies. Table 3 shows pertinent characteristics of the anuric heavyweight individuals. WeeklyKT/V> was found in 4(40%) heavyweight and 24 (40%) reference anurics (NS). Weekly Ccr > 54.4 L/l.73 m2 was noted in 6 (60%) heavyweight and 20 (33.3%) reference anurics (NS). The highest actual weights associated with acceptable KT/V and Ccr in anuria were in 2 men weighing and kg, respectively. DISCUSSION Heavy body weight will cause a large V and, consequently, low normalized urea and creatinine clearances in CPD (1,2,11). Nolph et at. studied the theoretical weight limitation for a weekly KT/V of 1.70 in anuria, when the usual CAPD schedule offour daily exchanges is applied (1). These authors calculated a maximal standard weight of 91 kg, or a urea

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4 volume of 52.8 L, consistent with weekly KTN of 1.70; if an exchange volume of 3.0 L is applied, transperitoneal urea equilibration is at 95%, and ultrafiltration volume is 1.5 L/24 hours. It is of interest that the mean Vof the heavyweight anuric subjects was 52.9 L in this study, with 50% of the values higher than 52.8 L (Table 3). The maximal actual weight allowing an acceptable KTN, even under the conditions defined in N olph et at.'s report (1), should be much higher than 91 kg, because heavyweight CPD patients are usually obese (Table 1), and V is much less than 0.58 of actual weight in obesity (11). For example, if V/weight is L/kg (Table 1), an actual weight of 113 kg corresponds to the standard weight of9l kg. V values in heavy, very tall, lean males would be higher than the values of this study and would increase the difficulty in achieving acceptable clearance levels. However, some degree of obesity is almost invariably present in subjects weighing loo kg, since this weight represents the ideal weight for a male cm tall andafemale213.3 cm tall. At the ideal weightof127.3 kg, a 20-year-old man would be cm tall, with V = L. Correction of obesity without alteration in the raw clearance values would cause large increases in KTN and Ccr (Figure 1). In summary: (1) heavyweight individuals on CPD are routinely obese; (2) obesity causes relatively low normalized clearances because of high V; (3) to compensate for obesity, large daily exchange volumes are needed, usually requiring more than four daily exchanges. A combination of nocturnal APD and daily CAPD allows both the delivery of large volumes of dialysate daily and the utilization of the peritoneal membrane 24 hours a day, and creates a level of inconvenience tolerable by most patients. This combination may be the preferred peritoneal dialysis modality for heavyweight subjects. Large volume APD alone is inefficient and probably inadequate in many instances, since it allows the use of the peritoneal membrane for only a fraction of the day. The maximal weight allowing acceptable normalized clearances in anuric subjects with combined CAPD-APD will be limited by both the daily exchange volume that can be delivered and the decreasing dialysate-toplasma urea and creatinine concentration ratio as dwell times get shorter. However, this maximal weight must be higher than 122 kg.

5 REFERENCES 1. Nolph KD, Jensen RA, Khanna R, Twardowski ZJ. Weight limitations for weekly urea clearances using various exchange volumes in CAPD.PeritDialInt 1994; 14: Tzamaloukas AH, Murata GH, Malhotra D, Fox L, Goldman RS, Avasthi PS. Creatinine clearance in continuous peritoneal dialysis: dialysis dose required for a minimal acceptable level. Perit Dial Int 1996; 16: Nolph KD, Moore HL, Twardowski ZJ, et al. Crosssectional assessment of weekly urea and creatinine clearances in patients on continuous ambulatory peritoneal dialysis. ASAIO J 1992; 38:M Tzamaloukas AH, Murata GH, Sena P. Assessing the adequacy of peritoneal dialysis. Perit Dial Int 1993; 13: Watson PE, Watson ID, Batt RD. Total body water volumes for adult males and females estimated from simple anthropometric measurements.am J Clin Nutr 1980; 32: Randerson DH, Chapman GV, Farrell PC. Amino acid and dietary status in long-term CAPD patients. In: Atkins RC, Farrell PC, Thomson N, eds. Peritoneal dialysis. Edinburgh: Churchill-Livingstone, 1981: Hamwi GT. Therapy. In: Danowski TS, ed. Changing dietary concepts in diabetes mellitus: diagnosis and treatment. New York: American Diabetes Association, Inc., 1964; 1: Tzamaloukas AH, Murata GH, Malhotra D, Sena P, Patron A. Urea kinetic modeling in continuous peritoneal dialysis patients. Effect of body composition on the methods for estimating urea volume of distribution. ASAIO J 1993; 39:M Murata GH, Tzamaloukas AH, Malhotra D, et al. Protein catabolic rate in patients on continuous peritoneal dialysis: its predictors and association with urea clearance indices. ASAIO J 1996; 42: Consensus Development Conference Panel. Morbidity and mortality of renal dialysis: an NIH consensus conference statement. Ann Intern Med 1994; 121: Tzamaloukas AH. Effect of edema on urea kinetic studies in peritoneal dialysis. Perit Dial Int 1994; 14: Tzamaloukas AH, Murata GH, Malhotra D, Fox L, Goldman RS, Avasthi PS. The minimal dose of dialysis required for a target KTN in continuous peritoneal dialysis. Clin Nephrol1995; 44: