Effects of Peritoneal Resting on Peritoneal Fluid Transport Kinetics

Methods

Peritoneal Resting Protocol

All the patients included in the present study were asked to stop CAPD and transfer to daytime ambulatory peritoneal dialysis (DAPD) with a nocturnal “empty belly” to let the peritoneal membrane rest overnight. CAPD was resumed after the patients reduced their hypertonic dialysate usage and retained adequate peritoneal fluid removal.

Fluid Kinetic Modeling

During a PD dwell, the rate of change in intraperitoneal volume in a given moment (dV/dt) is equal to the instantaneous net volume flow (J_V) occurring through the peritoneal membrane, which can be described according to the following phenomenological equation (8):

Equation (1) contains several exponential crystalloid osmotic pressure terms. Having the “lumped” rate constant “k” (min^-1) and other constant terms, ΔP, σ_pro · Δπ_pro, and L, Eq. (1) can be integrated over time (t), yielding the following (8):

In the present study we applied a nonlinear least-squares regression analysis to determine Q_T, K_e, and k from recorded UF volume-versus-time data. All computer simulations were performed with Matlab 6.5 (The MathWorks, Natick, Massachusetts, USA).

Evaluation of Membrane Transport Status

Peritoneal membrane transport status was evaluated in our center by means of the dialysis adequacy and transport test (DATT). The DATT was used in our center because it can provide a relatively accurate assessment of peritoneal membrane transport status while avoiding the complexity of performing a standard peritoneal equilibration test. The DATT method has been described by Rocco et al. (10).

Glucose Exposure

Daily glucose exposure was calculated as the product of the volume and the glucose concentration for all the daily exchanges. For example, for an individual who was using 4 x 2 L exchanges (3 x 2.27% and 1 x 3.86%), there would be 136.2 + 77.2 = 213.4 g of glucose per day.

Statistical Analysis

All values are given as mean ± SD unless otherwise specified and are considered statistically significant where p is less than 0.05. Paired t-test was used for comparisons of patients’ daily UF, computer simulated UF, daily instilled volume, daily glucose exposure, Q _T , K _e , k, and 24-hour dialysate-to-plasma ratio (D/P) of creatinine pre and post peritoneal resting.

Results

Seven CAPD patients (5 male and 2 female) were selected for the present study. Patients’ age was 66.77 ± 7.68 years (range 58.3 – 79.0 years), time on PD was 12.87 ± 10.02 months (range 7.5 – 34.8 months), and peritoneal resting time was 47.57 ± 41.57 days (range 13 – 136 days). Figure 1 shows the computer-simulated UF-versus-time curves before and after peritoneal resting. The post peritoneal resting UF volume was higher after a 3-hour dwell and the difference reached statistical significance at the 10th hour of the dwell (p < 0.05).

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Figure 1

Computer simulation of peritoneal fluid kinetics of pre (circles; n = 7) and post (triangles; n = 7) peritoneal resting. Significant difference marked ^* where p < 0.05 between pre and post peritoneal resting.

Table 1 shows changes in patients’ clinical and transport parameter before and after peritoneal rest. There was a statistically significant decrease in patients’ daily glucose exposure. The 24-hour D/P creatinine ratios decreased significantly after peritoneal resting, from 0.824 ± 0.055 to 0.707 ± 0.103, and the peritoneal fluid absorption rate was also significantly decreased after peritoneal resting: 1.011 ± 0.448 versus 0.625 ± 0.383 mL/minute. Table 2 shows changes in daily glucose exposure and peritoneal fluid absorption rate for each patient.

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Table 1

Changes in Patients’ Clinical and Transport Parameter Before and After Peritoneal Rest

	Pre peritoneal rest	Post peritoneal rest
Peritoneal creatinine clearance (mL/week)	42.40±15.24 (30.40-71.71)	43.17±5.41 (32.93-48.28)
Residual creatinine clearance (mL/ week)	7.29±6.83 (0-16.40)	6.31±7.37 (0-19.43)
Total creatinine clearance (mL/week)	49.68±15.23 (32.27-76.03)	49.48±9.65 (32.93-62.91)
Ultrafiltration (mL/day)	728.29±377.75 (54-1050)	761.29±288.03 (371-1264)
Instilled volume (mL/day)	7173.71±1465.98 (4000-8000)	6925.71±1618.94 (4000-8000)
Glucose exposure (g/day)	145.54±36.64 (90.8-181.6)	130.75±36.65 a (80.8-181.6)
Q T (mL)	580.86±182.12 (252-782)	522.00±188.81 (185-714)
K e (mL/min)	1.011±0.448 (0.436-1.700)	0.625±0.383 a (0.115-0.375)
k (min-1)	0.026±0.047 (0.004-0.131)	0.028±0.052 (0.003-0.145)
24-hour D/P creatinine	0.824±0.055 (0.775-0.901)	0.707±0.103 b (0.600-0.809)

Q _T = theoretical maximum drainable volume; K _e = sum of the rates of capillary and lymphatic fluid absorption from the peritoneal cavity; k = rate constant; D/P = dialysate-to-plasma ratio.

a

p ≤ 0.01 between pre and post peritoneal rest.

b

p ≤ 0.05 between pre and post peritoneal rest.

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Table 2

Changes in Daily Glucose Exposure and Peritoneal Fluid Absorption Rates for Each Patient

	Glucose exposure (g/day)		Ke (mL/min)
Patient	Pre	Post	Pre	Post
1	181.6	181.6	0.877	0.581
2	90.80	80.81	0.591	0.287
3	163.44	150.73	0.996	0.679
4	181.60	155.27	1.470	0.611
5	150.73	129.84	1.700	1.315
6	150.73	130.75	1.005	0.786
7	99.88	86.26	0.436	0.115

Pre = before peritoneal rest; Post = after peritoneal rest; K_e = the sum of the rates of capillary and lymphatic fluid absorption from the peritoneal cavity.

Discussion

The present study shows that peritoneal resting can restore peritoneal UF capacity by decreasing the peritoneal fluid absorption rate.

Peritoneal resting has been used to recover UF in patients with UF failure (5,11). Studies in an animal model also showed that peritoneal resting could reverse the structural changes of the peritoneal membrane induced by conventional PD fluid (6,12). An in vitro study suggested that human peritoneal mesothelial cells might recover from the stress of conventional peritoneal fluid exposure with a 24-hour rest (13). In our present study, there was no statistically significant increase in daily UF after peritoneal resting. Note, however, that we did not resume CAPD until we could decrease the use of hyper-tonic glucose solution. Therefore, the nonsignificant increase in UF volume was most likely due to the smaller glucose load after peritoneal resting, as shown in Table 1.

Along with the improved UF capacity, our data show that the D/P creatinine values and, more importantly, the peritoneal fluid absorption rate, K_e, both decreased significantly after peritoneal resting, suggesting that peritoneal resting could decrease peritoneal membrane solute transport rate and fluid absorption rate. K_e represents capillary and lymphatic fluid absorption from the peritoneal cavity (14). Fluid absorption from the peritoneal cavity adversely affects the efficacy of PD by reducing the potential for net fluid removal by 40% – 50% and by reducing small solute clearances by 15% – 20% (15). In the present study, patients’ UF capacity improved after peritoneal resting. As K_e decreased, less fluid absorption from the peritoneal cavity and daily UF could be achieved with a significantly smaller amount of daily glucose exposure. Although the peritoneal equilibration test is ideal compared to DATT, and DATT may be affected by dwell time, dialysate glucose concentration, and number of exchanges, the similar dwell times and dialysis exchanges and the even decreased glucose concentrations after the intervention indicated a decrease in peritoneal small solute transport. Furthermore, the kinetic simulations were based on the same glucose concentration used in the present study. Thus we believe the changes found in the present study must have been due to the intrinsic change in the peritoneal membrane. It has been suggested that a filter “cake” on the peritoneal surface may play an important role in peritoneal fluid absorption and this filter cake may be related to the integrity of mesothelial cells (16-18). Further studies are needed to explore the possible mechanisms of the effect of peritoneal resting.

There is a discrepancy between the values in Table 1 and the values in Figure 1. For Figure 1, the results of UF values from each patient were simulated, but not from the average coefficient values shown in Table 1. Therefore, it is not surprising to see this discrepancy. It is known that the glucose concentration in PD bags does not always exactly match the nominal concentration, and a more reliable estimate would have been obtained by sampling the fluid before the infusion and directly measuring the glucose concentration. We, however, have actually previously done this comparison and found that the difference could be neglected considering the variation in glucose measurements. As we followed strict patient inclusion criteria, the number of patients is relatively small (n = 7) in the present study. However, even with such a relatively small number of patients, we found significant differences in daily glucose exposure, K_e, and 24-hour D/P creatinine ratios between pre and post peritoneal rest.

Our study indicates that transferring patients to hemodialysis may not be necessary to restore peritoneal UF capacity. Our temporary transfer to DAPD with a nocturnal “empty belly” might be a very effective way to restore peritoneal UF capacity. Note, however, that by shortening the dwell time in DAPD compared to CAPD, one could achieve better UF. In our practice, when patients achieved volume control by shortening the dwell time, we tried to decrease the use of hypertonic glucose solution and intensify patient education to restrict salt and fluid intake to maintain good volume control. The use of fewer hypertonic glucose solutions during DAPD in our study may also have contributed to the restoration of membrane function. In our clinical practices, very high concentration glucose dialysate (3.86% glucose) is seldom used and, to us, using more than three exchanges of 2.27% dialysate is hypertonic dialysate use.

In conclusion, our study suggests that peritoneal resting can improve CAPD patients’ UF capacity and decrease the use of hypertonic dialysis solution. The improved UF capacity by peritoneal resting was due to decreased membrane solute transport rate and decreased peritoneal fluid absorption rate.