Peritoneal Sodium Removal Research Articles

P1160INCREASED REMOVAL RATES OF FLUID AND SODIUM DURING STEADY CONCENTRATION PERITONEAL DIALYSIS COMPARED TO ICODEXTRIN AND PERITONEAL EQUILIBRATION TEST

Abstract Background and Aims Removal of fluid and sodium may be a major challenge in PD, which can be addressed using icodextrin for the long dwells. Steady concentration PD (SCPD) with Carry Life® UF is a novel treatment modality where the intraperitoneal glucose concentration can be kept stable throughout the treatment maintaining ultrafiltration and sodium removal. This is performed by transferring a small volume of the dialysate into the device, where glucose is added and the dialysate returned to the patient. The present study was performed to compare the effect of SCPD with icodextrin and peritoneal equilibration test (PET) on ultrafiltration and sodium removal. Method Eight stable PD patients (high or high average transporters) were included in the study. Subjects were treated with three 5-hour Carry Life UF treatments using three different glucose doses (11, 14, 20 g/h). An initial fill with 1500 ml, 1.36% glucose PD solution was used. A small volume of dialysate was drained hourly to avoid overfill. An icodextrin 11-hour dwell (2000 ml, 7.5% Extraneal®), and a 4-hour PET (2000 ml, 2.27% glucose PD solution), were used as controls. Data expressed as mean ± SD, statistical analysis using one-way ANOVA, **p<0.01, ***p<0.001. Results The treatment time for icodextrin was 11.4±1.5 hours, for PET 4.1±0.1 hours, and for the Carry Life UF treatments 5.2±0.3 hours. Carry Life UF treatments generated increased ultrafiltration rates compared to icodextrin and PET (Figure a). The sodium removal rates with Carry Life UF treatments were also significantly increased compared to icodextrin and PET (Figure b). However, the total ultrafiltration volumes during Carry Life UF treatments were not significantly different compared to the icodextrin dwell (646±256, 739±312, 863±380, 595±239, ml/treatment for 11 g/h, 14 g/h, 20 g/h, and icodextrin, respectively). The ultrafiltration volume during PET was significantly lower than all other treatments (162±242 ml, p<0.001). Peritoneal sodium removal did not differ between Carry Life UF treatments and the icodextrin dwells (86±27, 92±33, 110±37, 88±34 mmol/treatment for 11 g/h, 14 g/h, 20 g/h, and icodextrin, respectively). Peritoneal sodium removal during PET was significantly lower than during the other treatments (22±33 mmol/treatment, p<0.01). Conclusion Treatments performed with Carry Life UF maintain a stable intraperitoneal glucose concentration during the entire dwell, resulting in higher ultrafiltration and sodium removal rates than for controls (PET and icodextrin). The fluid and sodium was removed during the 5-hour Carry Life UF treatments was comparable to the 11-hour icodextrin dwells. In summary, the increased removal rates of fluid and sodium during SCPD result in a more efficient treatment than conventional CAPD or icodextrin.

Development of a Direct Peritoneal Sodium Removal Technique with Salt Free Solution

Introduction Over time, interest in the concept of sodium and fluid removal via non-renal routes in heart failure (HF) has grown significantly. One approach to removing sodium and fluid without diuretics is peritoneal dialysis (PD). Traditional PD, however, is problematic in that it requires large intraperitoneal volumes with long dwell times while only offering limited sodium and fluid removal. Additionally, the solutions currently used in PD contain sodium concentrations that are nearly isotonic to serum, thus sodium removal is almost entirely driven by solute drag with ultrafiltration rather than diffusion down a concentration gradient. Hypothesis Utilization of salt free peritoneal solution will result in removal of a clinically significant amount of sodium and fluid. Methods Eighty kg anesthetized pigs (N=15) underwent surgical implantation of PD catheters via mini-laparotomy and venous and arterial access via cutdown. 1 liter of 10% dextrose in water was used as the sodium removal solution. In 5 pigs, we allowed a 6 hour dwell and the intraperitoneal volume was determined serially using indicator dilution technique with I-131 radiolabeled albumin (Daxor Corp., NY). 10 pigs underwent a 2 hour dwell with fluid volume measured by manual removal. To understand the effects of higher peritoneal solution volumes, 4 of these pigs then underwent 4 cycles of 2.5 L of 10% dextrose with 90 minute dwell times, for a total of 11 L cycled. These 4 animals had plasma volume measured with I-131 radiolabeled albumin (Daxor Corp., NY) prior to and after cycling was complete. Serial plasma and peritoneal fluid samples were obtained and glucose and electrolyte concentrations were determined. Results In the 5 animals with a 6 hour dwell, ultrafiltration approached 1.5 L and 5.1 +/- 0.4 grams of sodium was removed ( Fig. 1 a & 1b). In the 10 pigs that underwent a 2 hour dwell, an average of 0.9 +/- 0.2 L of ultrafiltration occurred with a corresponding 3.9 +/- 0.5 g of sodium removed ( Fig. 1 c). Despite a large sodium removal, the average decrease in serum sodium following the 2-hour dwell was only 2.2 +/- 0.3 mmol/L (P Fig. 1 d). Conclusion The direct peritoneal sodium removal approach is capable of removing large quantities of fluid and sodium with relatively small intraperitoneal volumes. Additional research is required to understand the safety/tolerability of this approach in humans, development of optimal solutions and protocols for fluid instillation and removal from the peritoneum.

Single Daily Icodextrin Exchange as Initial and Solitary Therapy.

Incremental dialysis utilizes gradually increasing dialysis doses in response to declines in residual kidney function, and it is the preferred renal replacement therapy for patients who have just transitioned to end-stage renal disease (ESRD). Incremental peritoneal dialysis (PD) may impose fewer restrictions on patients' lifestyle, help attenuate lifetime peritoneal and systemic exposure to glucose and its degradation products, and minimize connections that could compromise the sterile fluid path. In this study, we utilized a 3-pore kinetic model to assess fluid and solute removal during single daily icodextrin treatments for patients with varying glomerular filtration rates (GFR). Single icodextrin exchanges of 8 to 16 hours using 2- and 2.5-L bag volumes were simulated for different patient transport types (i.e., high to low) to predict daily peritoneal ultrafiltration (UF), daily peritoneal sodium removal, and weekly total (peritoneal + residual kidney) Kt/V (Kt/VTotal) for patients with residual renal GFRs ranging from 0 to 15 mL/min/1.73 m2. Daily peritoneal UF varied from 359 to 607 mL, and daily peritoneal Na removal varied from 52 to 87 mEq depending on length of icodextrin exchange and bag volume. Both were effectively independent of patient transport type. All but very large patients (total body water [TBW] > 60 L) were predicted to achieve adequate dialysis (Kt/VTotal ≥ 1.7) with a GFR of 10 mL/min/1.73 m2, and small patients (TBW: 30 L) were predicted to achieve adequate dialysis with a GFR of 6 mL/min/1.73 m2. A single daily icodextrin exchange can be tailored to augment urea, UF, and Na removal in patients with sufficient residual kidney function (RKF). A solitary icodextrin exchange may therefore be reasonable initial therapy for some incident ESRD patients.

Simple method to estimate daily sodium intake during measurement of dialysis adequacy in chronic peritoneal dialysis patients.

Restriction of dietary sodium intake for peritoneal dialysis (PD) patients is recommended, but there is limited information on the measurement and monitoring of sodium intake. We have developed a simple method to estimate daily sodium intake during the measurement of dialysis adequacy in PD patients. A total of 83 PD patients were enrolled in the study. The patients were divided into two groups based on residual renal function (RRF). We measured total sodium removal and estimated daily sodium intake using dietary recall for one day, during the assessment of dialysis adequacy. There were 39 patients in the RRF(-) group and 44 in the RRF(+) group. In both groups, and all patients, there were significant positive correlations between sodium intake and total sodium removal: RRF(-) group, r=0.598; RRF(+) group, r=0.577; total patients, r=0.595. There were linear relationships between dietary sodium intake and total sodium removal in both groups: RRF(-) group, sodium intake (mg/d) = 19.3 × peritoneal sodium removal (mEq/d) + 211;RRF(+) group, sodium intake (mg/d) = 15.4 × total sodium removal (mEq/d) + 609. All PD patients, sodium intake (mg/d) = 15.6 × total sodium removal (mEq/d) + 646. The measurement of total sodium removal during the assessment of dialysis adequacy could be an effective and simple method to estimate dietary sodium intake in PD patients. A dietary intake of 2,000 mg of sodium corresponds to a total sodium removal of approximately 87 mEq/d.

The effect of dietary salt restriction on hypertension in peritoneal dialysis patients.

To investigate the effect of dietary salt restriction on blood pressure levels, total sodium removal, and hydration status of peritoneal dialysis (PD) patients. Thirty-one stable PD patients who consulted a renal dietitian monthly for dietary recommendations, including restricted salt intake <5 g/day, and education about hypertension and hypervolemia were included in this study. Baseline and third month clinical and laboratory findings, bioelectrical impedance analysis results, and urinary and peritoneal sodium removal values were recorded. The mean age of the patients was 47.6 years and the mean time on PD was 39.6 months. The mean total sodium removal decreased slightly from 139.4 ± 69.1 to 136.2 ± 64.8 mmol/day (P > 0.05) for the whole sample, and from 164.3 ± 70.9 to 154.2 ± 72.3 mmol/day (P > 0.05) for the hypertensive subgroup (n: 17). Systolic blood pressure (from 134.3 ± 20.1 to 127.2 ± 19.5 mmHg, P: 0.01), diastolic blood pressure (from 83.2 ± 12.0 to 77.4 ± 10.5 mmHg, P: 0.01) and total body water (from 39.2 ± 10.9 to 38.3 ± 9.3 L, P: 0.04) decreased significantly. We demonstrated that even a little reduction in daily dietary sodium intake caused significant decreases in blood pressure levels and fluid overload.

Clinical Factors Associated with Sodium Removal in Peritoneal Dialysis Patients

A cross-sectional study was conducted in 156 clinically-stable peritoneal dialysis patients to identify the factors associated with sodium removal. Serum biochemistry, peritoneal function (modified peritoneal equilibration test [PET]) and the adequacy of dialysis were analysed in relation to sodium removal using multivariate linear regression. Factors significantly affecting peritoneal sodium removal included infusion volume and ultrafiltration volume per 24 h, sodium dip in the first hour of PET and sodium difference between serum and fresh dialysate. Factors significantly affecting total sodium removal included ultrafiltration and urine volume per 24 h, sodium dip in the first hour of PET and sodium difference between serum and fresh dialysate. With traditional dialysate, adequate fluid removal is required to ensure sufficient sodium removal, but a low-sodium dialysate may prevent sodium retention. Sodium removal should be included in evaluation of the adequacy of dialysis.

A Combined Crystalloid and Colloid PD Solution as a Glucose-Sparing Strategy for Volume Control in High-Transport APD Patients: A Prospective Multicenter Study

Evidence is accumulating that the continuous exposure to high glucose concentrations during peritoneal dialysis (PD) is an important cause of ultrafiltration (UF) failure. The cornerstone of prevention and treatment of UF failure is reduction of glucose exposure, which will also alleviate the systemic impact of significant free glucose absorption. The challenge for the future is to discover new therapeutic strategies to enhance fluid and sodium removal while diminishing glucose load and exposure using combinations of available osmotic agents. To investigate in patients on automated PD (APD) with a fast transport pattern whether there is a glucose-sparing advantage to replacing 7.5% icodextrin (ICO) during the long dwell with a mixed crystalloid and colloid PD fluid (bimodal UF) in an attempt to promote daytime UF and sodium removal while diminishing the glucose strength of the dialysate at night. A 2 parallel arm, 4 month, prospective nonrandomized study. PD units or university hospitals in 4 French and Belgian districts. During the 4-month intervention period, net UF and peritoneal sodium removal during the long dwell when treated by bimodal UF was about 2-fold higher than baseline (with ICO). The estimated percent change (95% confidence interval) from baseline in net daytime UF for the bimodal solution was 150% (106% - 193%), versus 18% (-7% - 43%) for ICO (p < 0.001). The estimated percent change from baseline in peritoneal sodium removal for the bimodal solution was 147% (112% - 183%), versus 23% (-2% - 48%) for ICO (p < 0.001). The estimated percent change from baseline in UF efficiency (24-hour net UF divided by the amount of glucose absorbed) was significantly higher (p < 0.001) when using the bimodal solution was 71%, versus -5% for ICO. Prescription of bimodal UF during the day in APD patients offers the opportunity to optimize the long dwell exchange in a complete 24-hour APD cycle. The current study demonstrated that a bimodal solution based on the mixing of glucose (2.6%) and icodextrin (6.8%) achieved the double target of significantly improving UF and peritoneal sodium removal by exploring a new concept of glucose-sparing PD therapy.

The effects of low-sodium peritoneal dialysis fluids on blood pressure, thirst and volume status

Background. Poor ultrafiltration is associated with worse outcomes in peritoneal dialysis (PD) patients. This might in part reflect problems associated with salt and water excess. Increasing the diffusive component of peritoneal sodium removal using low-sodium PD fluids might have beneficial effects on blood pressure (BP), thirst and fluid status that could translate into clinical benefits.Methods. Using a multicentre, prospective, baseline controlled (1 month), non-randomized intervention (2 months) design, two novel solutions designed from predictions using the three-pore model were investigated. In group A ([Na+] = 115 mmol/l), the glucose (G) was increased to 2.0% to compensate for reduced osmolality whereas in group B ([Na+] = 102 mmol/l), it was unchanged (2.5%). Both solutions were substituted for one 3- to 5-h exchange per day and no change was made to the rest of the dialysis regime.Results. Ten patients in group A and 15 in group B completed the study. Both solutions resulted in significant increases (30–50 mmol/dwell) in diffusive sodium removal during the test exchanges, P < 0.001. Ultrafiltration was maintained in group A but reduced in group B. Ambulatory nocturnal mean BP fell in group A [93.1 ± 10.6 mmHg (±SD) versus 85.1 ± 10.2 mmHg, P < 0.05], but was stable in group B (95.4 ± 9.4 versus 95.1.1 ± 10.7 mmHg, NS). Thirst reduced independent of appetite and mood in both groups by 2 months, more markedly in group A. Indices of fluid status, including TBW by bioimpedance and D dilution also improved in group A, P < 0.05, whereas weight increased in group B.Conclusions. Increasing the diffusive component of sodium removal whilst maintaining ultrafiltration is associated with improvements in BP, thirst and fluid status. The lack of effect seen with uncompensated low-sodium dialysate suggests that these benefits cannot be achieved by manipulation of dialysate sodium removal alone. These observations provide valuable information of the design of future randomized studies to establish the clinical role for low-sodium dialysis fluids.

The Prescription of Peritoneal Dialysis

In addition to the maintenance of normal extracellular electrolyte composition, the prescription of continuous peritoneal dialysis (CPD) should address four other specific issues: (i) prevention of uremia by achievement of adequate clearance of azotemic substances, (ii) prevention of progressive expansion of the extracellular volume by adequate peritoneal ultrafiltration, (iii) prevention of loss of residual renal function, and (iv) prevention of deterioration of the peritoneal membrane structure and function. Urea clearance, in the form of Kt/V(Urea), is the index of removal of azotemic substances proposed by current guidelines. The target total (renal plus peritoneal) Kt/V(Urea) is >or=1.7 weekly. To provide the desired peritoneal Kt/V(Urea) (K(p)t/V(Urea)), the prescription of peritoneal dialysis must provide a daily drain volume (Dv) defined by the clearance equations as Dv = V x (K(p)t/V(Urea))/(D/P(Urea)), where V is body water obtained from published anthropometric formulas, K(p)t/V(Urea) = (1.7 - renal Kt/V(Urea))/7 and D/P(Urea) is the dialysate-to-plasma urea concentration ratio at the dwell time prescribed. Computer programs obtain the relevant D/P(Urea) values from formal studies of peritoneal transport. In the absence of these studies (for example, at initiation of CPD), D/P(Urea) values can be obtained from published studies with similar dwell times. Body size, indicated by V, is the major determinant of the K(p)t/V(Urea) limit provided by a given CPD schedule. Other obstacles to achievement of adequate urea clearance are created by poor patient compliance, inaccuracies of the anthropometric formulas estimating V, and mechanical complications of CPD that lead to retention of dialysate in the body. The main requirements for the prescription of adequate ultrafiltration are knowledge of the individual peritoneal transport characteristics, monitoring of urinary volume, and restriction of dietary sodium intake. Excessive dietary sodium intake is the major cause of extracellular volume expansion in CPD. Ideally, sodium intake should be kept at the level of total (peritoneal plus renal) sodium removal. Preventing the loss of residual renal function involves avoidance of nephrotoxic influences in the form of medications, radiocontrast agents, urinary obstruction and infection, and possibly other influences, such an elevated calcium-phosphorus product and anemia. Use of the lowest dialysate dextrose concentration that will allow adequate ultrafiltration is currently the most widespread practical measure of prevention of peritoneal membrane deterioration. Formulation of biocompatible dialysate is a major ongoing research effort and may greatly enhance the success of CPD in the future.

Use of Icodextrin during Nocturnal Automated Peritoneal Dialysis Allows Sustained Ultrafiltration While Reducing the Peritoneal Glucose Load: A Randomized Crossover Study

Optimization of ultrafiltration and preservation of the peritoneal membrane are desirable objectives in peritoneal dialysis (PD) patients. Mixtures of glucose- and non-glucose-based solutions may help to meet both targets simultaneously. To analyze the effects, in terms of ultrafiltration and peritoneal glucose load, of including icodextrin-based dialysate in the nocturnal schedule of patients undergoing automated PD (APD). Following a randomized crossover design, 17 APD patients underwent two 10-day study periods under identical prescription (including amino acid-based solution for the night schedule), except for the substitution of 2 L glucose-based dialysate in the nocturnal mixture (control) by a similar amount of icodextrin-based dialysate (icodextrin phase) in one period. Dependent variables included ultrafiltration, sodium removal, peritoneal glucose load, and residual renal function. We measured serum and urine levels of icodextrin metabolites at the end of each phase. Ultrafiltration was marginally higher during the icodextrin phase (median 815 vs 763 mL/day, p = 0.07), while peritoneal sodium removal was similar in both phases (74 vs 71 mmol/L/day). Peritoneal glucose load (median 67.5 vs 104.0 g/day, p < 0.005) and absorption (14.0 vs 35.6 g/day, p < 0.005) were lower during the icodextrin phase. Diuresis was also modestly lower during the icodextrin phase (500 vs 600 mL/day, p < 0.05). Serum levels of icodextrin metabolites were moderately higher in the icodextrin phase (p < 0.005) in patients both on and off diurnal icodextrin. Inclusion of amino acid- and icodextrin-based solutions in the nocturnal schedule of APD patients may allow sustained ultrafiltration and sodium removal while significantly reducing the peritoneal glucose load in these patients.

Peritoneal Sodium Mass Removal in Continuous Ambulatory Peritoneal Dialysis and Automated Peritoneal Dialysis: Influence on Blood Pressure Control

Background/Aim: Sodium and water retention is common in peritoneal dialysis patients and contributes to cardiovascular disease. As peritoneal sodium removal depends partly on dwell time, and automated peritoneal dialysis (APD) often uses short dwell time exchanges, the aim of this study was to compare the 24-hour peritoneal sodium removal in APD and standard continuous ambulatory peritoneal dialysis (CAPD) patients and to analyze its possible influence on blood pressure control. Methods: A total of 53 sodium balance studies (30 in APD and 23 in CAPD) were performed in 36 stable peritoneal dialysis patients. The 24-hour net removal of sodium was calculated as follows: M = ViCi – VdCd, where Vd is the 24-hour drained volume, Cd is the solute sodium concentration in Vd, Vi is the amount of solution used during a 24-hour period, and Ci is the sodium concentration in Vi. Peritoneal sodium removal was compared between APD and CAPD patients. Residual renal function, serum sodium concentration, daily urinary sodium losses, weekly peritoneal Kt/V and creatinine clearance, 4-hour dialysate/plasma creatinine ratio, proportion of hypertonic solutions, net ultrafiltration, systolic and diastolic blood pressures, and need for antihypertensive therapy were also compared between the groups. Results: Peritoneal sodium removal was higher (p < 0.001) in CAPD than in APD patients. There were no significant differences in residual renal function, serum sodium concentration, urinary sodium losses, peritoneal urea or creatinine clearances, 4-hour dialysate/plasma creatinine ratio, or proportion of hypertonic solutions between groups. The net ultrafiltration was higher in CAPD patients and correlated strongly (r = 0.82; p < 0.001) with peritoneal sodium removal. In APD patients, peritoneal sodium removal increased significantly only in those patients with a second daytime exchange. The systolic blood pressure was higher (p < 0.05) in APD patients, and the proportion of patients with antihypertensive therapy was also higher in APD patients, although no significant relationship between blood pressure values and amount of peritoneal sodium removal was found. Conclusions: The 24-hour sodium removal is higher in CAPD than in APD patients, and there is a trend towards better hypertension control in CAPD patients. As hypertension control and volume status are important indices of peritoneal dialysis adequacy, our results have to be considered in the choice of the peritoneal dialysis modality.