Cnossen, Trijntje T.*; Konings, Constantijn J.A.M.†; Fagel, Wouter J.‡; van der Sande, Frank M.*; van Geel, Koos*; Leunissen, Karel M.*; Kooman, Jeroen P.*
Fluid and sodium balance are crucial for the management of patients on peritoneal dialysis (PD). Inadequate fluid and sodium removal by dialysis are potential risk factors for overhydration, which is significantly related to hypertension, left ventricular hypertrophy, and higher cardiovascular morbidity and mortality in PD patients.1–4
In clinical practice, PD patients are either treated with continuous ambulatory peritoneal dialysis (CAPD) or automated peritoneal dialysis (APD), in the latter usually with more rapid exchange cycles during nighttime followed by a daytime dwell. Although previously, APD was primarily used to treat patients with a high membrane transport status, it has become increasingly popular with patients for lifestyle reasons.
Because of the shorter dwell times in APD sodium sieving, possibly resulting in a reduced sodium removal, is more pronounced. Consequently, a higher prevalence of overhydration and hypertension was suggested in APD patients,5,6 although the use of icodextrin for the long dwell might improve sodium removal in CAPD as well as in APD patients.7–9 However, there are few studies that compared fluid and sodium balance, as well as blood pressure and volume control between APD and CAPD patients after the widespread introduction of new dialysis solutions such as icodextrin.10
The hypothesis of the study is that sodium and daily fluid removal is significantly lower, whereas extracellular volume (ECV) is significantly higher in patients with a low transport status treated with APD compared with CAPD, whereas in patients with a high transport status of the peritoneal membrane treated with APD, ECV is significantly lower and fluid removal is significantly higher.
The aim of the current study was to compare fluid state, ambulatory blood pressure, and sodium removal between patients treated with APD and CAPD.
In this multicenter study 44 patients were included from three dialysis centers (Medical Centre Leeuwarden, Catharina Hospital Eindhoven, and Maastricht University Medical Centre+, the Netherlands). Fluid state, peritoneal transport, residual renal function (RRF), peritoneal ultrafiltration volume, urine volume, and blood pressure were compared in a cross-sectional design between patients treated with APD and CAPD. Exclusion criteria were acute intercurrent infection and peritonitis during the 4 weeks preceding the peritoneal equilibration test (PET).
A total of 44 stable patients (26 men, 18 women; mean age 60.2 ± 13.7 yr) were enrolled in the study. The causes of renal insufficiency were diabetes mellitus (n = 14), glomerulonephritis (n = 6), autosomal dominant polycystic kidney disease (ADPKD) (n = 4), IgA glomerulonephritis (n = 4), athero/glomerulosclerosis (n = 7), urological disorder (n = 2), antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (n = 2), Goodpasture syndrome (n = 1), multiple myeloma (n = 1), stenosis of renal artery (n = 1), syndrome of Alagille (n = 1), and unknown origin (n = 1). The mean duration of PD was 25.0 ± 24.8 (range 2–129) months. Mean diuresis was 1172 ± 808 ml/24 hr and RRF 6.7 ± 5.0 ml/min. Patients were treated with APD or CAPD according to the preference of the patient or treating physician based on PET results (Table 1). All patients used commercially available dialysis solutions (Baxter Healthcare, IRL, Dublin, Ireland). Dialysis prescription was at the discretion of the treating physician. All patients were advised to follow a sodium restricted diet (2000 mg sodium per day) by dietary counseling.
Patients came to their own dialysis center to perform a standardized 3.86% glucose PET of 4 hr. First, the overnight PD fluid was drained, and fluid status was measured by multifrequency bioimpedance analysis. Thereafter, the abdomen was filled with 3.86% glucose solution to perform the PET. Thereafter, 24 hr ambulatory blood pressure measurements were performed. The day before the PET, 24 hr dialysate and urine collections were performed. The Ethics Committee of the Catharina Hospital, Eindhoven, the Netherlands, primarily approved the study protocol, followed by approval of the Institutional Review Boards of the other participating centers. All patients gave their written informed consent.
Peritoneal transport characteristics. The transport characteristics of the peritoneal membrane were characterized using a standardized PET after a 4 hr dwell with a 3.86% glucose solution. Dialysis adequacy, determined by Kt/Vurea and weekly creatinine clearance normalized to body surface area was calculated using PD Adequest 2.0 (Baxter Healthcare).
Fluid state. Fluid state was assessed with a multifrequency bioimpedance measurement. Two different devices were used; 35 patients were measured by Xitron 4200 (Xitron Technologies Inc, San Diego, CA) and nine patients by whole body bioimpedance spectroscopy (Body composition monitor [BCM] — Fresenius Medical Care D GmbH, Bad Homburg, Germany). Measurements were performed in a standard fashion while the patient was lying supine on a flat, nonconductive bed and with an empty abdomen. Multifrequency (5–500 kHz), alternating currents were introduced at distal electrodes on the hands (just proximal to the phalangeal-metacarpal joint in the middle of the dorsal side of the hand) and the feet (proximal to the transverse [metatarsal] arch on the superior side of the foot), and resistances were measured by proximal electrodes (to the wrist midway between the styloid process, to the ankle midway between the malleoli). Extracellular water (ECW) assessed by Xitron 4200, was predicted from a general mixture theory (Cole-Cole model): water compartments were directly calculated from resistance values, assuming specific resistances of ECV provided by the manufacturer. Extracellular volume assessed by BCM, was determined using a recently modified equation developed by Moissl et al.11,12 Whole body ECW (w ECV) and ICV (w ICV) measured by the BCM were recalculated by Xitron using Equations 1, 2, and 3, respectively.13
Equation (Uncited)Image Tools
Equation (Uncited)Image Tools
Equation (Uncited)Image Tools
where RE and RI are extra- and intracellular resistances in Ω, H is body height in cm and W is body weight (BW) in kilograms. The resistivity constants in ECV calculation (ρECV) were 40.5 Ω * cm for men and 39.0 Ω * cm for women, and in ICV calculation (ρICV) were 273.9 Ω * cm and 264.9 Ω * cm, respectively. KB is a constant factor (KB = 4.3), correcting whole body measurements by relating the relative proportions of the leg, arm, trunk, and height.
Overhydration was expressed by the slope normovolemia model, described by Chamney.14 The slope normovolemia is calculated as ECW:BW with 0.239 L/kg in men and 0.214 L/kg in women.14
24 hr Ambulatory blood pressure. In all patients, 24 hr blood pressure measurements were performed using a Spacelabs Oscillometric Blood Pressure Monitor (Space-Labs Medical, Redmond, WA). Blood pressure was measured every 20 minutes during the day (from 8 A.M. until 22 P.M.) and every 60 minutes during the night (from 22 P.M. until 8 A.M).
Measurements in plasma and dialysate. Plasma and dialysate creatinine, urea, sodium, and glucose were analyzed using an Advia 1650 (Siemens Medical Solutions Diagnostics, San Francisco, CA); sodium concentrations in plasma and dialysate were analyzed with an ion-selective electrode using an indirect method. Urea and glucose were analyzed with enzymatic methods and creatinine with a compensated alkaline picrate method. N-terminal pro-B-type natriuretic peptide (NT-proBNP) was measured using the proBNP assay for the Elecsys 2010 (Roche Diagnostics GmbH, Mannheim, Germany).
Results are expressed as mean values and standard deviations (SD). The Student t-test was used for differences between APD and CAPD. Mann–Whitney U tests were used where appropriate. All statistical analyses were made using SPSS 16.0 (SPSS Inc, Chicago, IL); p < 0.05 was considered significant.
The study was powered to detect a difference in ECV of 0.03 L/kg body weight between APD and CAPD patients, assuming an SD of 0.03 L/kg.15 To show this difference a sample size of 16 patients per group would be needed (α = 0.05, power 80%).
Twenty patients (12 men, 8 women) treated with APD and 24 patients (14 men, 10 women) treated with CAPD were included. Baseline characteristics of patients treated with APD and CAPD are given in Table 1. Mean systolic (SBP) and diastolic blood pressure (DBP) were comparable between APD and CAPD patients (Table 1) (not significant [NS]). In effect, 72.7% of patients used one or more antihypertensive or cardioprotective agents (excluding diuretics). Mean number of antihypertensive drugs was not significantly different between APD and CAPD patients, although there appeared to be some differences in the classes of antihypertensive drugs used between both groups (Table 2). Patients treated with APD had a lower sodium concentration in dialysate, although dialysate sodium removal was not significantly different between both groups (Table 2). However total daily removal of sodium was lower in APD as compared with CAPD patients (p = 0.039). Parameters of fluid state of patients treated with APD and CAPD are shown in Table 3. There were no significant differences between patients treated with both modalities. Also NT-pro BNP levels were not significantly different between both groups. The median value in APD patients was 188 pmol/L (interquartile range 79–366) and 248 pmol/L (interquartile range 93–884) in CAPD patients (Table 4; NS).
When comparing patients (combining APD and CAPD) treated with (n = 28) and without icodextrin (n = 16) there were no significant differences in fluid status (–0.01 ± 0.05 vs. 0.0 ± 0.02 L/kg, respectively), despite a lower urinary sodium removal in patients treated with icodextrin (68 ± 41 vs. 112 ± 182 mmol/24 hr). Dialysate sodium removal (111 ± 90 vs. 70 ± 83 mmol/24 hr) and peritoneal ultrafiltration (854 ± 705 vs. 577 ± 648 ml/24 hr) were not significantly different between patients treated with icodextrin and those who were not.
The main findings of the current study are that blood pressure control, assessed by ambulatory blood pressure measurements, and fluid state were not significantly different between patients treated with APD and CAPD. These findings are in line with the study by Boudville et al.,8 who studied only APD patients but observed an acceptable volume and blood pressure control in APD patients with a liberal use of icodextrin. In the more recent articles of Davison et al.10 and Van Biesen et al.16 also, no difference in fluid status or blood pressure control between APD and CAPD was observed. In those studies also, a majority of patients were treated with icodextrin; whereas in the study of Davison et al.,10 significantly more APD patients used icodextrin as compared with the CAPD group, in our study, the percentage was not significantly different. Dialysate sodium concentration was lower in APD patients, possibly reflecting increased sodium sieving, but possibly because of the higher ultrafiltration volume, dialysate sodium removal was not significantly different between both groups. Nevertheless, total daily sodium removal was higher in CAPD as compared with APD patients. It is possible that the higher daily sodium removal in our CAPD patients is caused by a combination of higher dialysate sodium removal, which might not have reached significance because of the relatively small sample size and a higher urinary sodium removal. In the study of Davison et al.,10 dialysate sodium removal was lower in APD compared with CAPD patients without evidence for differences in volume status or blood pressure control. Still, in view of the relation between sodium removal and mortality, observed by Ates et al.,17 these differences should not be neglected, although the causal relationship remains uncertain.
Comparing our patient population with that of Davison et al.10 and Boudville et al.,8 volume state, which was assessed by Xitron 4200BIS in all three studies, was reasonably comparable. The ECW: TBW (total body water) ratio, which was the sole marker of fluid state in the study of Davison et al.,10 was somewhat lower in our study, which might also be related to the higher residual renal function in our patients.18 Indeed, total sodium removal was higher in our study population as compared with the patients of Davison et al.,10 whereas dialysate sodium removal was comparable. In the EuroBCM in PD study, 63.7% of the total study cohort used icodextrin, which was associated with less overhydration and more underhydration.16 More than 25% of the study cohort was severely fluid overloaded.
Although it is difficult to compare results of previous studies1–4 with the results of the current study, as the computational model between the Xitron 4000 and 4200 is not entirely comparable, volume status in PD patients appeared to be relatively well controlled in most recent studies. In our study, the mean normalized overhydration index according to the Chamney approach, was around zero.14 Also blood pressure in the patient populations of Boudville et al.8 and Davison et al.,10 as well as in the current study, was reasonably well controlled, in contrast to earlier observations.19 Whether the improvement in volume and blood pressure control in more recent studies is because of the more liberal use of icodextrin, or to an increased awareness for volume status in general in PD patients cannot be deduced from the current study.
In the current study, the slope normovolemia level developed by Chamney et al.,14 which corrects for sex, was used as the parameter for volume status. The reason that we did not use the ECW:TBW ratio as the prime marker of overhydration, despite the recent establishment of normalized values,20 is because this ratio might be increased either by overhydration, by a reduction in lean body mass caused by malnutrition, or by both. Until now, undisputed cutoff levels and normalizing techniques for overhydration by the Xitron 4002 have not been definitively established. The best validated normal values in bioimpedance technology in dialysis patients so far have been developed for the BCM,11,12 which was derived from Xitron technology but with an improved mathematical model. In addition, the comparable fluid status, as also the NT-pro BNP levels, which were found to be related to cardiac load in previous studies,21 were not significantly different between both groups.
Icodextrin use was widespread in all three studies. Previous studies9,22 showed a beneficial effect of icodextrin on fluid status. In the study of Boudville et al.,8 normalized ECV was lower in the patients treated with icodextrin, whereas in the current study no difference in volume status was observed between patients treated with icodextrin and those who were not. However, urine sodium removal was significantly lower in those patients treated with icodextrin, and therefore the absence of differences might be explained by confounding by indication.
The limitations of the current study are the observational nature, cross-sectional design, and relatively small peritoneal dialysis population. However, the group of APD and CAPD patients appeared to be reasonably well matched. Moreover, detailed analysis of fluid state, natriuretic peptides, and 24 hr ambulatory blood pressure measurements were available in our patients.
In conclusion, in this cross-sectional study, fluid state and ambulatory blood pressure measurements were comparable between patients treated with CAPD or APD despite a lower total daily sodium removal in the latter group. In general, in agreement with recent studies, fluid status and blood pressure appeared to be reasonably well controlled in both APD and CAPD patients.
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