Effects of icodextrin in automated peritoneal dialysis on blood pressure and bioelectrical impedance analysis
Graham Woodrow,
Brian Oldroyd1,
Gillian Stables,
Jill Gibson,
John H. Turney and
Aleck M. Brownjohn
Renal Unit, Leeds General Infirmary and
1 Centre for Bone and Body Composition Research, University of Leeds, Leeds, UK
 |
Abstract
|
---|
Background. Glucose absorption from glucose-based dialysis fluids limits ultrafiltration from the daytime dwell in automated peritoneal dialysis (APD). Icodextrin may allow greater ultrafiltration during the daytime period in APD, enhancing fluid control.
Methods. A 7.5% icodextrin dialysate was compared with a 2.27% glucose dialysate for the daytime dwell in 14 subjects on APD. Blood pressure, weight and body water compartments estimated by multifrequency bioelectrical impedance (MFBIA) were determined in subjects using 2.27% glucose as the daytime dwell and then repeated 1 month after switching to icodextrin.
Results. Icodextrin resulted in symptomatic hypotension requiring reduction of antihypertensive medication in six of the 14 patients. Despite this reduction in treatment, systolic blood pressure fell from 142.4 (23.9) mmHg to 122.9 (17.7) mmHg, P<0.005, and diastolic blood pressure tended to fall from 82.8 (9.8) mmHg to 76.8 (10.1) mmHg, P=0.075. Change in systolic blood pressure significantly correlated with changes in weight (r=0.62, P<0.05) and MFBIA estimates of total body water (TBW) (r=0.56, P<0.05), extracellular water (ECW) (r=0.79, P<0.002), extra/intracellular water ratio (ECW/ICW) (r=0.72, P<0.01) and derived resistances Recf of ECW (r=-0.69, P<0.01) and Rinf of TBW (r=-0.66, P<0.02). Changes in diastolic blood pressure significantly correlated with changes in ECW (r=0.64, P<0.02) and ECW/ICW ratio (r=0.58, P<0.05), and almost significantly with Recf (r=-0.51, P=0.08) and Rinf (r=-0.52, P=0.07) estimated by MFBIA, but not with changes in weight or TBW.
Conclusions. Use of icodextrin for the daytime dwell in APD results in improved fluid balance and blood pressure control compared with 2.27% glucose. MFBIA detected clinically important changes in fluid content in these patients.
Keywords: automated peritoneal dialysis; bioelectrical impedance; body water; hypertension; icodextrin; ultrafiltration
 |
Introduction
|
---|
Loss of salt and water homeostasis is an invariable feature of progressive chronic renal failure (CRF). In dialysis patients, hydration depends on the balance of fluid intake and fluid removal by dialysis and residual urine output. Intake and dialytic fluid removal are adjusted to attain an ideal dry weight as judged by relatively crude clinical and sometimes radiological criteria [1]. Hypertension is a common manifestation of fluid overload in dialysis patients and may occur without other clinical evidence of fluid excess. Hypertension and chronic fluid overload contribute to the high incidence of cardiovascular disease in patients on renal replacement therapy [2].
In peritoneal dialysis, excess fluid is removed from the body by the osmotic effect of solutes in the peritoneal dialysis fluid. Glucose is used commonly for this purpose but has a number of disadvantages. Absorption of dialysate glucose limits it effectiveness as an osmotic agent and contributes to the adverse metabolic effects of peritoneal dialysis such as hyperlipidaemia [3] and body fat accumulation [4]. The high concentrations of glucose in dialysis solutions and the generation of advanced glycation end-products (AGEs) may lead to long-term peritoneal membrane damage, limiting technique survival [5]. Icodextrin is a glucose polymer developed as an alternative osmotic agent to glucose which produces sustained ultrafiltration for the long overnight dwell in continuous ambulatory peritoneal dialysis (CAPD) [6]. It may be similarly effective for the long daytime dwell in automated peritoneal dialysis (APD), enhancing fluid removal whilst avoiding use of hypertonic glucose for long periods of time [7,8].
Bioelectrical impedance analysis (BIA) is a simple technique with high precision for measurement of body water compartments and body composition. It has been studied extensively in renal disease, with most work looking at measurement of acute fluid changes or its ability to measure body compartments on single occasions. There is little information on its ability to detect important changes in hydration or body composition over a longer time period, such as would be applicable to longitudinal patient monitoring.
Here we describe the effect of fluid balance on blood pressure control and body water estimated by BIA in patients who took part in a study of the use of icodextrin in APD [8]. The aims were to determine the relationship between change in hydration and blood pressure control, and to assess the ability of BIA to detect clinically important changes in body water content over a 1 month period.
 |
Subjects and methods
|
---|
Fourteen patients (12 male and two female) entering a study of icodextrin in APD [8] underwent more detailed study of changes in blood pressure and fluid status. Exclusions included patients with hypotension or problems due to raised intra-abdominal pressure. All other APD patients with a daytime dwell were considered, without selection according to clinical criteria or peritoneal membrane function (two high, eight high average and four low average transport). Median patient age was 47.8 years (range 26.869.2 years). APD was performed with the AMP 80/2 cycler in three patients and the Homechoice cycler (Baxter) in 11 patients. Night-time exchange volumes were 10 l in three patients, 12.5 l in one patient and 15 l in 10 patients, with a median night-time dialysis time of 9 h (range 8.510.2 h) and mean glucose concentartion 2.06%, SD 0.44. Prior to the study, the daytime exchange consisted of 2.27% glucose in all patients, with volumes of 1.5 l in 11 patients and of 2 l in three patients.
Blood pressure, weight and body water compartments estimated by multiple frequency bioelectrical impedance (MFBIA) were measured at the start of study, whilst patients were receiving 2.27% glucose for the daytime dwell. Patients then switched to icodextrin (Baxter) for the daytime dwell whilst continuing usual fluid intake, and were assessed again after 1 month when these measurements were repeated. The overnight APD cycles were unchanged throughout the study. Blood pressure was recorded to the nearest 5 mmHg using a mercury sphygmomanometer with patients in a sitting position after 5 min rest. MFBIA measurements were made by the Xitron 4000B multifrequency bioelectrical impedance spectrum analyser (Xitron Technologies, San Diego, CA). The analyser measures whole-body impedance and phase angle at 50 different frequencies, range 5500 kHz. A ColeCole plot of measured reactance and resistance at these frequencies allows extrapolation to estimate resistance at zero frequency (Recf ), corresponding to the resistance of extracellular water (ECW), and at infinite frequency (Rinf ), corresponding to total body water (TBW). From these, Ricf, the resistance of intracellular water (ICW), is calculated and the water volumes estimated from equations based on the Hanai mixture theory (see Appendix). This analysis was performed by software provided with the analyser (Version 1.00d). Resistance (R), reactance (Xc) impedance (Z) and the relationship between R and Xc (phase angle) were also recorded for the individual frequencies of 5, 50 and 200 kHz. Measurements were made using the standard tetrapolar technique with current injection and sensing electrodes placed on the left wrist and ankle [9]. Measurements were made with patients in the supine position with limbs abducted after 10 min rest, with a dry peritoneal cavity.
Statistical analysis comprised the comparison of means of groups of measurements in the same subjects by the paired t-test, and correlations were performed using the Pearson correlation coefficient. Comparisons of numbers of patients with positive or negative ultrafiltration with the different solutions was by the
2 test. Precision of BIA estimated from pairs of measurements performed 1 month apart in 15 healthy subjects demonstrated coefficients of variation over this time period for ECW 2.4%, ICW 3.4%, ECW/ICW 4.2%, TBW 1.9%, Recf 2.9% and Ricf 3.3%.
The study was approved by the local research ethics committee and all patients gave written informed consent.
 |
Results
|
---|
The mean daytime dwell volume was 1.61 l (SD 0.21). The mean daytime ultrafiltration volume was greater for icodextrin (0.27, SD 0.32 l) than for 2.27% glucose (-0.26, SD 0.33 l), P<0.0001. Twelve out of 14 patients had net fluid absorption from the daytime dwell with 2.27% glucose, but only one failed to achieve net fluid removal from the daytime dwell with icodextrin (
2 P<0.0001).
Symptomatic hypotension occurred in six subjects during the first month of icodextrin to a degree requiring reduction in number of antihypertensive agents or dosage (Table 1
). Despite this reduction in medication, there was a significant reduction in systolic blood pressure and a tendency for diastolic blood pressure to be reduced (Table 2
). During this time, weight reduced almost significantly by a mean of 0.8 kg (P=0.06). There was a significant reduction in ECW and TBW estimated by MFBIA and an almost significant reduction in ECW/ICW ratio (Table 2
). In 13 patients remaining on APD with an icodextrin daytime dwell after 3 months, systolic blood pressure was reduced similarly at 125.8 (24.7) mmHg (P<0.05) and diastolic blood pressure was lower than at the start at 77.3 (9.0) mmHg (P<0.05).
View this table:
[in this window]
[in a new window]
|
Table 1. Changes in blood pressure and antihypertensive medication in individual patients at start of study and after receiving icodextrin for the daytime dwell for 1 month (drugs being changed in bold)
|
|
View this table:
[in this window]
[in a new window]
|
Table 2. Changes in blood pressure, body weight and body water compartments (estimated by MFBIA) after 1 month use of icodextrin for the daytime dwell compared with the start of the study (values mean and SD)
|
|
Changes in electrical data are shown in Table 3
. Estimated resistance of extracellular fluid (Recf ) and at infinity (Rinf, reflecting TBW) increased significantly, but there was no significant change in resistance of intracellular fluid (Ricf ). Electrical measurements were also analysed at frequencies of 50 kHz (the standard frequency used in single frequency BIA) and at 5 and 200 kHz, which reflect ECW and TBW, respectively [10]. There were significant changes in Z, R, Xc and phase angle at all three frequencies (except change in phase angle at 5 kHz, P=0.06).
View this table:
[in this window]
[in a new window]
|
Table 3. Changes in electrical parameters estimated by MFBIA after 1 month use of icodextrin for the daytime dwell compared with the start of the study (values mean and SD)
|
|
Despite the confounding effect of reduction in antihypertensive medication, reduction in systolic blood pressure at 1 month significantly correlated with reductions in weight (r=0.62, P<0.05) and MFBIA estimates of TBW (r=0.56, P<0.05), ECW (r=0.79, P<0.002) (Figure 1
), ECW/ICW ratio (r=0.72, P<0.01), Rinf (r=-0.66, P<0.02) and Recf (r=-0.69, P<0.01). Changes in diastolic blood pressure at 1 month significantly correlated with changes in ECW (r=0.64, P<0.02) and ECW/ICW ratio (r=0.58, P<0.05), and almost significantly with Recf (r=-0.51, P=0.08) and Rinf (r=-0.52, P=0.07) estimated by BIA, but not with changes in weight or TBW.

View larger version (14K):
[in this window]
[in a new window]
|
Fig. 1. Correlation of change in systolic blood pressure with change in extracellular water (ECW) measured by MFBIA (r=0.79, P<0.002).
|
|
Change in systolic blood pressure also correlated with change in impedance at the individual frequencies studied: 5 kHz (r=-0.62, P=0.05), 50 kHz (r=-0.62, P<0.05) and 200 kHz (r=-0.63, P<0.05). Change in systolic blood pressure did not correlate with change in phase angle (except at 50 kHz, r=-0.59, P<0.05) or with change in reactance. There were no significant correlations of change in diastolic blood pressure and change in these electrical parameters (except change in phase angle at 200 kHz, r=-0.61, P<0.05).
There were almost significant relationships between peritoneal membrane characteristics (4 h dialysate/plasma creatinine ratio from PET test) with changes in TBW (r=-0.52, P=0.066) and changes in ECW (r=-0.55, P=0.053), but not with change in blood pressure.
 |
Discussion
|
---|
Although dialysis techniques prolong survival and reverse symptoms of renal failure, patients receiving renal replacement therapy have a much greater mortality than a healthy control population. Efforts to optimize the adequacy of dialysis therapies have focused on clearance of uraemic toxins, especially small solute clearances [11]. However, adequate treatment of CRF should include many other aspects, such as acidosis, bone metabolism, anaemia, nutritional status, rehabilitation and quality of life. Despite emphasis on measurement of clearances, it is increasingly suspected that control of hypertension and hydration is as important in determining outcome of dialysis patients [12]. The remarkable survival rates of haemodialysis patients from Tassin, where long hours of dialysis and careful attention to fluid balance result in excellent blood pressure control without the need for antihypertensive medication in most patients, is evidence for the importance of fluid balance to hypertension and development of cardiovascular complications in CRF [2].
Evidence exists for the presence of excess fluid retention in patients on peritoneal dialysis compared with haemodialysis [13]. High peritoneal membrane transport characteristics are an adverse prognostic factor in CAPD, and one possible explanation is that poor ultrafiltration in these patients leads to chronic fluid overload [14]. It is suggested that fluid retention causes dilutional hypoalbuminaemia in CAPD, and thus the link between serum albumin concentrations and survival in CAPD may be due partly to complications of fluid overload [15].
Methods of assessing hydration in dialysis patients are crude and insensitive [1]. Clinical assessment alone cannot exclude fluid overload without removing fluid to the point of symptomatic hypovolaemia. A number of methods have been proposed for assessment of hydration, including measurement of inferior vena caval diameter by ultrasound and assay of atrial natriuretic factor [1]. Most promising and widely studied of these methods is BIA [1622]. Utilizing the different penetration of the intracellular space by different frequency currents, MFBIA provides information regarding ICW and ECW which may be of more value than TBW alone in assessing hydration and nutritional state. The high precision of BIA and ease of use give it a potential clinical role in longitudinal monitoring of patients with renal failure to allow early detection of changes in hydration and/ or nutrition before they are clinically detectable. There is little information regarding the use of BIA in long-term clinical monitoring of patients where changes in BIA have been related to changes in gold standard methods of assessing body composition or changes in other important clinical variables. A study in paediatric haemodialysis patients suggests that changes in BIA preceded changes in dry weight made on clinical grounds [23].
Although the changes in TBW and ECW in this study are probably overestimated by MFBIA when compared with weight changes, and there are no gold standard measurements such as isotope dilution to confirm the fluid volume changes, the strong relationship of MFBIA changes in this study to blood pressure changes induced by fluid removal by icodextrin is a further indicator of the possible clinical value of this technique. It has been suggested that the ability of BIA to estimate body compartments may be attributed more to the contribution of the weight term in predictive equations than to the actual electrical data. The relationship of changes in blood pressure to changes in the terms Recf and Rinf and changes in impedance measurements is strong evidence for the importance of the actual electrical measurements in MFBIA.
The data presented in this study show a significant short-term improvement in control of hypertension in patients on APD commencing use of icodextrin for the daytime dwell. This study is limited by patient numbers and lack of a control population, the method of blood pressure measurement and changes in antihypertensive medication. Some of these limitations actually may have tended to reduce the significance of observed changes and the relationships between change in blood pressure and the variables studied. The effect of icodextrin on fluid balance and hypertension in CAPD and APD warrants further larger randomized controlled studies with longer follow-up. Icodextrin may allow improved control of fluid balance to be achieved in peritoneal dialysis, with possible benefits in patient outcome. MFBIA detects clinically important changes in body water compartments. Further studies are needed to define its potential role in clinical practice for longitudinal monitoring of body composition in CRF.
 |
Appendix
|
---|
Derivation of body water compartments from MFBIA spectrum analysis
Total body impedance and phase angle measurements are made at 50 frequencies from 5 to 500 kHz. A ColeCole plot of the measured reactance and resistance values over the frequency range is made. Extrapolation determines the resistance at zero and infinite frequencies, corresponding to the resistances of extracellular water (Recw) and total body water (Rinf ). The resistance of the intracellular fluid Ricw is calculated from:
 | (00A) |
Using Hanai mixture theory, the body water compartments can be calculated [24].
Volume of extracellular water
 | (00B) |
where Ht is height (cm) and Wt is weight (kg)
 | (00C) |
where KB is a geometry factor relating to volumes of leg, arm and trunk,
ecw is resistivity of ECW (
/cm),
icw is resistivity of ICW (
/cm) and DB is body density (kg/l).
Volume of intracellular water
 | (00D) |
where k
=
icw/
ecw
Volume of total body water
 | (00E) |
 |
Acknowledgments
|
---|
We are grateful to Baxter Healthcare for providing financial support for this study. This work was undertaken by the Leeds Teaching Hospital NHS Trust who received funding from the NHS Executive: the views expressed in this publication are those of the authors and not necessarily those of the NHS Executive.
 |
Notes
|
---|
Correspondence and offprint requests to: Dr Graham Woodrow, Consultant in Renal Medicine, Renal Unit, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, UK. 
 |
References
|
---|
-
Leunissen KML. Fluid status in haemodialysed patients. Nephrol Dial Transplant1995; 10: 153155[ISI][Medline]
-
Charra B, Calemard E, Ruffet M. et al. Survival as an index of adequacy of dialysis. Kidney Int1992; 41: 12861291[ISI][Medline]
-
Boeschoten EW, Zuyderhoudt FMJ, Krediet RT, Arisz L. Changes in weight and lipid concentrations during CAPD treatment. Peritoneal Dial Int1988; 8: 1924[ISI]
-
Fenström A, Hylander B, Moritz Å, Jacobsson H, Rössner S. Increase of intra-abdominal fat in patients treated with continuous ambulatory peritoneal dialysis. Peritoneal Dial Int1998; 18: 166171[ISI][Medline]
-
Mahiout A, Ehlerding G, Brunkhorst R. Advanced glycation end-products in the peritoneal fluid and the peritoneal membrane of continuous ambulatory peritoneal dialysis patients. Nephrol Dial Transplant1996; 11 [Suppl. 5]: 26[ISI][Medline]
-
Mistry CD, Gokal R, Peers E and the MIDAS Study Group. A randomized multicenter clinical trial comparing isosmolar icodextrin with hyperosmolar glucose solutions in CAPD. Kidney Int1994; 46: 496503[ISI][Medline]
-
Posthuma N, ter Wee PM, Verbrugh HA, Oe PL, Peers E, Sayers J et al. Icodextrin instead of glucose during the daytime dwell in CCPD increases ultrafiltration and 24-h dialysate creatinine clearance. Nephrol Dial Transplant1997; 12: 550553[Abstract]
-
Woodrow G, Stables G, Oldroyd B, Gibson J, Turney JH, Brownjohn AM. Comparison of icodextrin and glucose solutions for the daytime dwell in automated peritoneal dialysis. Nephrol Dial Transplant1999; 14: 15301535[Abstract]
-
Lukaski HC, Johnson PE, Bolonchuk WW, Lykken GI. Assessment of fat-free mass using bioelectrical impedance measurements of the human body. Am J Clin Nutr1985; 41: 810817[Abstract]
-
Hannan WJ, Cowen SJ, Plester CE, Fearon KCH, deBeau A. Comparison of bio-impedance spectroscopy and multi-frequency bio-impedance analysis for the assessment of extracellular and total body water in surgical patients. Clin Sci1995; 89: 651658[ISI][Medline]
-
Churchill DN, Taylor DW, Keshaviah PR and the CANUSA Peritoneal Dialysis Study Group. Adequacy of dialysis and nutrition in continuous peritoneal dialysis: association with clinical outcomes. J Am Soc Nephrol1996; 7: 198207[Abstract]
-
Coles GA. Have we underestimated the importance of fluid balance for the survival of PD patients? Peritoneal Dial Int1997; 17: 321326[ISI][Medline]
-
Rottembourg J. Residual renal function and recovery of renal function in patients treated by CAPD. Kidney Int1993; 43 [Suppl. 40]: S106S110
-
Blake PG. What is the problem with high transporters? Peritoneal Dial Int1997; 17: 317320[ISI][Medline]
-
Jones CH, Smye SW, Newstead CG, Will EJ, Davison AM. Extracellular fluid volume determined by bioelectric impedance and serum albumin in CAPD patients. Nephrol Dial Transplant1998; 13: 393397[ISI][Medline]
-
Woodrow G, Oldroyd B, Turney JH, Davies PSW, Day JME, Smith MA. Measurement of total body water by bioelectrical impedance in chronic renal failure. Eur J Clin Nutr1996; 50: 676681[ISI][Medline]
-
Kushner RF. Bioelectrical impedance analysis: a review of principles and applications. J Am Coll Nutr1992; 11: 199209[Abstract]
-
Chumlea WC, Guo SS. Bioelectrical impedance and body composition: present status and future directions. Nutr Rev1994; 52: 123131[ISI][Medline]
-
Fisch BJ, Spiegal DM. Assessment of excess fluid distribution in chronic hemodialysis patients using bioimpedance spectroscopy. Kidney Int1996; 49: 11051109[ISI][Medline]
-
Piccoli A. Identification of operational clues to dry weight prescription in hemodialysis using bioimpedance vector analysis. Kidney Int1998; 53: 10361043[ISI][Medline]
-
Ho LT, Kushner RF, Schoeller DA, Gudivaka R, Spiegel RM. Bioimpedance analysis of total body water in hemodialysis patients. Kidney Int1994; 46: 14381442[ISI][Medline]
-
Bradbury MG, Brocklebank JT, Smye SW, Davies PSW. Total body water measurement in renal insufficiency. Pediatr Nephrol1996; 10: 195199[ISI][Medline]
-
Edefonti A, Ardissino G, Loi S, Damiani B, Mercuri M, Ghio L et al. Assessment of dry weight by bioimpedance analysis (BIA) in children on chronic haemodialysis (HD): a first breakthrough. J Am Soc Nephrol1997; 8: 233
-
deLorenzo A, Andreoli A, Matthie J, Withers P. Predicting body cell mass with bioimpedance using theoretical methods: a technological review. J Appl Physiol1997; 82: 15421558[Abstract/Free Full Text]
Received for publication: 5. 7.99
Revision received 8. 2.00.