Contrasting effects of amphotericin B and the solvent sodium desoxycholate on peritoneal transport

To distinguish amphotericin B effects on peritoneal transport from those of the solvent, sodium desoxycholate, dialyses in intact rabbits with either substance added intraperitoneally were compared to controls. Powered amphotericin B added to instilled dialysis fluid increased peritoneal ultrafiltration from 0.31 to 0.44 ml/kg/min (p less than 0.02), but did not affect mass transport (e.g. urea clearance changed from 0.86 to 1.04 ml/kg/min). In contrast, 10 mg of desoxycholate induced peritoneal irritation and raised clearances of urea (0.76-1.34 ml/kg/min), potassium, phosphate and dextrose, but did not affect ultrafiltration. Intraperitoneally, 1 mg/kg of desoxycholate changed clearances inconsistently, but lowered the ultrafiltration rate from 0.33 to 0.21 ml/kg/min. The dialysate-plasma dextrose gradient dissipated faster with 10 mg/kg of desoxycholate. Amphotericin B tended to raise ultrafiltration per osmotic gradient and mass transport of sodium. Selective increase in fluid flux results from amphotericin B, not its solvent.     

The mechanism of dextrose-enhanced peritoneal mass transport rates

The mechanism whereby hypertonic dextrose affects peritoneal transport was investigated in a short-term model of peritoneal dialysis using alert intact rabbits. During control (1.5% dextrose) dialyses osmotic ultrafiltration was 0.28 mg/kg/min, the clearance of potassium was 0.98, urea 0.54, phosphate 0.32, and dextrose (reverse) 0.21 ml/kg/min. With 4.25% dextrose, the ultrafiltration rate increased to 0.73 ml/kg/min (P less than 0.02), but solute transport did not increase despite the added convective flux. The posthypertonic exchanges did not differ from control despite the effect of residual dialysate contaminating this peritoneal lavage. By indicator dilution residual volume averaged 12% of total dialysate volume. Acute volume expansion by intravenous dextrose after desoxycorticosterone acetate (DOCA) pretreatment increased the ultrafiltration coefficient, potassium and urea clearances significantly, and DOCA alone was ineffective. It is suggested that in uremic humans hypertonic dextrose dialysis increases peritoneal mass transport rates because the absorbed dextrose causes extracellular volume expansion that cannot be eliminated promptly. No evidence of a direct effect of dextrose augmenting peritoneal permeability was detected.     

Prolonged intraperitoneal dwell decreases ultrafiltration coefficient in rabbits

In rabbits undergoing peritoneal dialysis, hypertonic (6% dextrose) dialysis solution increased the net ultrafiltration rate (UF) from 233 to 462 microL/kg/min, which was not proportional to the increment in the osmotic gradient, so the ultrafiltration coefficient decreased. As intraperitoneal dwell of hypertonic dialysate was prolonged, the gross and net UFs and ultrafiltration coefficients decreased, and the UF per dextrose absorption declined. The decrement in UF was multifactorial, including a component of fluid and solute stagnation, increasing the distance over which osmotic forces must exert their effects. Excessively hypertonic dialysis fluid should be used only briefly to achieve ultrafiltration efficiently and to avoid the high dextrose loading.     

Maximum ultrafiltration rates during peritoneal dialysis in rats

It has been suggested that filtration pressure equilibrium could occur in peritoneal capillaries during peritoneal dialysis with very hypertonic exchanges. Rats were exposed to peritoneal dialysis solutions using 16 ml instillations, 30 minute cycles, and dextrose concentrations from 1.4 to 20 g%. There was a plateau in ultrafiltration per exchange at mean osmotic gradients above 360 mOsm/kg H2O near 12.5 ml/ex (0.42 ml/min). The findings are also compatible with filtration pressure equilibrium predictions at an effective capillary plasma flow of 0.84 ml/min and a filtration fraction near 50%. Studies with cardiovascular drugs (norepinephrine i.v., nitroprusside i.p., and dobutamine i.v.) showed no effects on the maximum ultrafiltration rates. This might indicate that flow is rather fixed because of known microcirculatory effects of solutions themselves.     

Osmotic Ultrafiltration with Dextran Sodium Sulfate Potential for use in Peritoneal Dialysis

Dextran sodium sulfate was evaluated in vitro as a potential non-absorbable osmotic agent for peritoneal dialysis. It was compared to poly(sodium acrylate) which has been shown previously to be effective in rats, but probably toxic. Dextran sodium sulfate induced osmotic ultrafiltration rates as high as 20 ml/min in water but only 2 ml/min in solution containing non-polymer electrolytes presumably because of Gibbs-Donnan effects. Compared to acrylate the dextran polymer has less sodium per gram, lower osmotic activity of polymer sodium, and yields less ultrafiltration at given transmembrane osmolalities. A nontoxic polymer more like acrylate would seem more promising as an osmotic agent for peritoneal dialysis.     

Predictors of a favourable response to icodextrin in peritoneal dialysis patients with ultrafiltration failure

BACKGROUND AND AIMS: Icodextrin is a starch-derived glucose polymer that causes sustained ultrafiltration in long dwells in peritoneal dialysis. The aim of this study was to assess factors that were predictive of an increment in ultrafiltration following the introduction of icodextrin in patients with refractory fluid overload. METHODS: Thirty-nine patients (20 male/19 female, mean age 57.7 +/- 2.4 years) on peritoneal dialysis were enrolled in a prospective pretest/post-test, open-label study. All patients had symptomatic fluid overload refractory to fluid restriction (<800 mL/day), frusemide doses of 250 mg or more daily, optimization of dwell time and use of hypertonic dextrose. An icodextrin exchange was substituted for a 4.25% dextrose exchange for the long-dwell period. RESULTS: After 1 month, median (interquartile range) 24 h ultrafiltration volume increased by 500 mL (interquartile range: 50-1000). An increase in ultrafiltration volume correlated positively with the dialyate : plasma creatinine ratio at 4 h (r = 0.498, P = 0.001) and negatively with the ratio of dialysate glucose concentrations at 4 and 0 h (r = -0.464, P = 0.003). On multivariate regression analysis, high transporter status was predictive of a greater ultrafiltration response to icodextrin relative to dextrose peritoneal dialysis exchanges. Age, sex, race, peritoneal dialysis duration, peritoneal dialysis modality, diabetes mellitus, baseline albumin, and baseline ultrafiltration volume were not significantly correlated with the change in ultrafiltration volume. CONCLUSION: Icodextrin significantly augments ultrafiltration volumes in patients with refractory fluid overload. A high peritoneal membrane transporter status is the best predictor of a favourable ultrafiltration response to icodextrin.     

Amphotericin B, mercury chloride and peritoneal transport in rabbits

BACKGROUND: The effect of glucose-induced ultrafiltration in peritoneal dialysis is dependent on the presence and function of ultrasmall transendothelial cell water channels. The mercury-sensitive aquaporin-1 was thought to represent these transcellular pores. Amphotericin B (ampho B) has been reported to increase ultrafiltration in both experimental and patient studies. The objective of this study was to investigate the hypothesis that intraperitoneal ampho B increases and mercury chloride inhibits aquaporin-1-mediated water transport in a chronic peritoneal dialysis model in the rabbit. MATERIAL AND METHODS: Eighteen female New Zealand White rabbits were included for peritoneal catheter implantation. Peritoneal transport parameters were determined in all rabbits by standard peritoneal permeability analysis (SPAR) with 3.86% glucose-based dialysis solution during a one-hour dwell prior the intervention SPARs, as a control. Ampho B (0.06 mg/kg body weight) was added to the dialysate for 3 (n = 9) or 5 consecutive days (n = 5) before investigation. Four rabbits were investigated after 3-day i.p. 0.6 mg/kg body weight ampho B. In 3 rabbits 0.06 mg/kg body weight liposomal ampho B was administered i.p. during 3 days before intervention SPAR. Fifteen rabbits were investigated during a one-hour dwell with 0.1 mM HgCl2 containing 3.86% glucose-based dialysis solution, while they were anesthetized. Three of these underwent in vivo fixation with glutaraldehyde prior to the HgCl2 SPAR to prevent toxic effects of mercury on peritoneal tissues. RESULTS: Intraperitoneal administration of ampho B did enhance the change in intraperitoneal volume during a one-hour dwell after 3-day i.p. treatment with the low dose (p < 0.02), but it did not affect peritoneal solute permeability. This was likely mediated by transcellular water channels, but not by aquaporin-1. No beneficial effects on the ultrafiltration were found with prolonged treatment or with the higher dose. Ultrafiltration decreased (8 ml/4 h to 1 ml/4 h, p < 0.03) after i.p. administration of HgCl2 with and without in vivo fixation, accompanied by a significant decrease in aquaporin-mediated water transport, estimated as the sieving of sodium (p < 0.001). Marked increases in the clearances of macromolecules were found after i.p. HgCl2 administration due to toxic effects: total protein clearance from 97 to 172 microl/min, p < 0.005, and albumin clearance from 59 to 158 microl/min, p < 0.005. These changes were less pronounced after in vivo fixation. CONCLUSION: Ampho B has likely no clinical relevance in treatment of ultrafiltration failure in PD patients. Aquaporin-mediated water transport could be inhibited and consequently ultrafiltration was reduced by i.p. administration of mercury chloride in our rabbit model.     

Polyanions and Glucose as Osmotic Agents in Simulated Peritoneal Dialysis

Peritoneal dialysis solutions contain glucose as an osmotic agent to obtain ultrafiltration. Due to rapid absorption, glucose does not sustain high ultrafiltration during long exchanges. Nonabsorbable polyanions might be effective as osmotic agents when suspended in electrolyte solution. Concentrations of freely diffusible ions should be in Gibbs-Donnan equilibrium with plasma electrolytes. The ideal proportion of diffusable to polymerbound cation concentrations is unknown. To obtain concentrations of free ions in equilibrium with plasma, it is assumed that the polymer solution dialyzed against a polyelectrolyte solution of the desired composition (with hydraulic pressure higher on the polymer side) will approach the same thermodynamic activity as the electrolyte solution. Subsequently, if transmembrane pressure is released, osmotic ultrafiltration will occur in proportion to the hydrostatic pressure applied during polymer solution preparation. Polyacrylate solution so prepared was compared with a commercial dextrose dialysis solution in an in vitro simulation of peritoneal dialysis. With dwell times up to 24 h, sustained ultrafiltration with polymer was observed, whereas, with dextrose, ultrafiltration ceased after 8 h. Concentrations of diffusible bivalent cations in polyacrylate were lower than intended due to avid polymer complexing; however, dextran sulfate solutions were developed to contain desired concentrations of diffusible electrolytes. The conclusion is that some polymer solutions might be useful in clinical settings when high sustained ultrafiltration is needed.     

Kinetics of peritoneal dialysis in children: role of lymphatics

Intraperitoneal fluid is absorbed continuously by convective flow into the peritoneal cavity lymphatics. We evaluated the role of lymphatic absorption in the kinetics of peritoneal dialysis during standardized four hour exchanges in six children using 40 ml/kg of 2.5% dextrose dialysis solution. Cumulative lymphatic absorption averaged 10.4 +/- 1.6 ml/kg and reduced the total net transcapillary ultrafiltration during the dwell time by 73 +/- 10%. Due to the considerable lymphatic absorption rate, maximum intraperitoneal volume was observed before osmolar equilibrium. Extrapolated to four study exchanges per day, lymphatic absorption decreased the potential daily drain volumes in the children by 27 +/- 5% and daily peritoneal urea and creatinine clearances by 24 +/- 4% and 22 +/- 5%, respectively. Compared with four hour exchanges using two liters of 2.5% dextrose dialysis solution in 10 adult CAPD patients with average peritoneal transport, the children had more rapid equilibration of urea, greater absorption of dialysate glucose, higher lymphatic absorption and lower net ultrafiltration (P less than 0.01 to P less than 0.05). Lymphatic absorption therefore causes a relatively greater reduction in net ultrafiltration and solute clearances in children than in adults.     

L-carnitine is an osmotic agent suitable for peritoneal dialysis

Excessive intraperitoneal absorption of glucose during peritoneal dialysis has both local cytotoxic and systemic metabolic effects. Here we evaluate peritoneal dialysis solutions containing L-carnitine, an osmotically active compound that induces fluid flow across the peritoneum. In rats, L-carnitine in the peritoneal cavity had a dose-dependent osmotic effect similar to glucose. Analogous ultrafiltration and small solute transport characteristics were found for dialysates containing 3.86% glucose, equimolar L-carnitine, or combinations of both osmotic agents in mice. About half of the ultrafiltration generated by L-carnitine reflected facilitated water transport by aquaporin-1 (AQP1) water channels of endothelial cells. Nocturnal exchanges with 1.5% glucose and 0.25% L-carnitine in four patients receiving continuous ambulatory peritoneal dialysis were well tolerated and associated with higher net ultrafiltration than that achieved with 2.5% glucose solutions, despite the lower osmolarity of the carnitine-containing solution. Addition of L-carnitine to endothelial cells in culture increased the expression of AQP1, significantly improved viability, and prevented glucose-induced apoptosis. In a standard toxicity test, the addition of L-carnitine to peritoneal dialysis solution improved the viability of L929 fibroblasts. Thus, our studies support the use of L-carnitine as an alternative osmotic agent in peritoneal dialysis.     

Isoproterenol Enhancement of Peritoneal Permeability

As peritoneal dialysis is inefficient enough to be time-consuming and sometimes clinically ineffective, we have evaluated pharmacologic enhancement of peritoneal permeability. Peritoneal dialyses were performed in New Zealand white rabbits by instillation of 50 ml/Kg of isotonic dialysis solution of standard composition. Mean peritoneal clearance of creatinine was 0.60 ml/Kg/min and urea was 0.80 ml/Kg/min, each decreasing as intraperitoneal dwell was prolonged (by. 011 ml/Kg/min or less). With 0.04 uMl/Kg of isoproterenol administered intraperitoneally, clearances increased to 0.91 and 1.30 ml/Kg/min (p <0.01). When isoproterenol was added to the dialysis solution one hour or more before instillation, the increment in clearances was less. Instillation of dialysis solution 24 hours after addition of a higher dose of isoproterenol (0.2 uM/Kg) did not increase clearances above control. No effect of isoproterenol on bulk flow of water, associated with the osmotic effect of dextrose, was demonstrated. As peritoneal clearances increased, the ratio creatinine clearance : urea clearance did not decrease, consistent with increased peritoneal permeability as well as blood flow.     

Albumin-based Solutions for Peritoneal Dialysis: Investigations with a Rat Model

Abstract: To evaluate albumin, an osmotic agent for peritoneal dialysis, the peritoneal fluid and solute transport were investigated during a 4-h single cycle peritoneal dialysis with albumin-based dialysis solutions. Two different albumin solutions were used in 15 normal Sprague-Dawley rats: isotonic 7.5% albumin solution (ADS 1, n = 7) and a combined 7.5% albumin and 1.36% glucose solution (ADS 2; n = 8). A standard 1.36% Dianeal solution was used to provide control values (n = 6). The rate of the intraperitoneal volume change (Q_v) was positive during the initial 90 min with ADS 2 and during the initial 60 min with Dianeal 1.36% solution but negative with ADS 1. The peritoneal bulk flow reabsorption rate, Q_a, was similar in all three groups. The estimated rate of transcapillary ultrafiltration (Q_u=Q_v+Q_j was positive with all three solutions throughout the dialysis. With ADS 1, Q_u increased gradually during the initial 90 min and then remained stable, but it decreased with ADS 2 and Dianeal 1.36% solution. Q_u with ADS 2 did not differ from that with Dianeal 1.36% solution during the initial 60 min, but it was significantly higher during the latter part of dialysis. The value of Q_u during the last 2 h of dialysis was 0.026 ± 0.010 and 0.025 ± 0.009 ml/min with ADS 1 and ADS 2, respectively, and it was significantly higher than that with Dianeal 1.36% solution (0.005 ± 0.007 ml/ min; p< 0.017). After 4 h of dialysis, 76.1 ± 10.2 and 78.8 ± 11.1% of the initial amount of albumin remained in the peritoneal cavity with ADS 1 and ADS 2, respectively. Since a positive value of Q_u was maintained for at least 4 h during dialysis with the two albumin-based solutions and was significantly higher after 4 h of dialysis than with the Dianeal 1.36% solution, and since (Q_a) was similar with the three solutions, the present findings indicate that the differences in the Q_v values are due to the differences in the transcapillary ultrafiltration rate (Q_U). Furthermore, ADS 2, a solution containing both crystalloid and colloid osmotic agents, resulted in higher and more prolonged ultrafiltration than did the conventional glucose solution. After 4 h of dialysis, about 20–25% of the initial amount of albumin was absorbed, indicating that albumin-based dialysis solutions may compensate for the protein loss into dialysate in continuous ambulatory peritoneal dialysis (CAPD) patients. The results of the present study may provide useful reference data in the evaluation of alternative osmotic agents.     

Ultrafiltration by hyperosmotic peritoneal dialysis fluid excludes intracellular solutes

During peritoneal dialysis, progressive increments in the osmotic gradient increase ultrafiltration rate. Solute transport by convective flux is thereby raised but there is no preferential increase in potassium clearance. The data imply that ultrafiltrate derives from extracellular fluid alone. Mesothelial cells appear to resist solute and water flux in response to an immediately adjacent osmotic gradient.     

Pharmacological reduction of lymphatic absorption from the peritoneal cavity increases net ultrafiltration and solute clearances in peritoneal dialysis

Lymphatic drainage from the peritoneal cavity occurs mainly via the subdiaphragmatic stomata and significantly reduces net ultrafiltration and solute clearances during long-dwell peritoneal dialysis. Intraperitoneal cholinergic drugs constrict these stomata and may reduce peritoneal cavity lymphatic absorption. We evaluated ultrafiltration kinetics, solute transport, and lymphatic drainage during single hypertonic exchanges in rats using 2.5% dextrose dialysis solution with and without added neostigmine. Net ultrafiltration was enhanced in the neostigmine group (p less than 0.01) by a reduction in cumulative lymphatic absorption (p less than 0.01) and without an increase in total transcapillary ultrafiltration during the dwell time. Likewise solute clearances were significantly augmented with neostigmine primarily due to the increase in dialysate drain volume (p less than 0.01) since dialysate/serum solute ratios were unchanged. Pharmacological manipulation of peritoneal lymphatic absorption provides an alternative means of increasing the efficiency of long-dwell peritoneal dialysis without altering peritoneal transport of solutes and water.     

New peritoneal dialysis fluids: practical use for children

In recent years several new peritoneal dialysis solutions have come onto the market. These solutions differ from the conventional ones with respect to osmotic agent, buffer, and/or calcium concentration. Icodextrin-containing solutions are characterized by slow, but sustained ultrafiltration. Experience in both adults and children has been favorable for the long dwell period, giving rise to both increased ultrafiltration and clearances. The use of icodextrin during the daytime seems ideal in patients on nightly intermittent peritoneal dialysis with a low peritoneal ultrafiltration rate. However, long-term experience still has to be obtained, particularly in children. The application of pH-neutral solutions, containing bicarbonate, lactate, or a bicarbonate/lactate mixture as a buffer, has shown better preservation of peritoneal cells and better tolerance. The standard calcium concentration of 1.75 mmol/l of the dialysis solution is too high in many situations. Individual strategies for an adequate calcium balance are required depending on age, clinical situation, and oral intake of calcium and vitamin D metabolites.     

Ultrafiltration and effective peritoneal blood flow during peritoneal dialysis in the rat

The dependence between maximum net ultrafiltration rate (nUFR) created by 15% dextrose dialysis solution and effective peritoneal capillary blood flow (EPBF) estimated by the diffusive mass transport coefficient (KBD) and peritoneal clearance (Cp) of CO2 gas was evaluated during 30 minute, 15 ml peritoneal dialysis exchanges in anesthetized rats (N = 18). The values of KBD for CO2 suggested a mean EPBF of 1.9 +/- 0.1 (SEM) ml/min for isosmotic exchanges and 2.7 +/- 0.2 ml/min for hyperosmotic ones with a mean maximum nUFR of 0.43 +/- 0.01 ml/min. Cp of CO2 measured after the first five minutes of dwell underestimated EPBF. In normally hydrated rats, maximum nUFR was achieved when the peritoneal filtration fraction was 32 +/- 2%. This value is similar to the glomerular filtration fraction in rats of 30%. Thus, our results indicate the following relationships: EPBF = (approximately 3 x maximum nUFR)/(1 - hematocrit). EPBF was about six times greater than maximum nUFR and exceeded about 57 times nUFR obtained under isosmotic conditions. These differences between EPBF and nUFR suggest normal EPBF is not a major limiting factor for maximum ultrafiltration achieved during peritoneal dialysis.     

Mini-peritoneal equilibration test: A simple and fast method to assess free water and small solute transport across the peritoneal membrane

BACKGROUND: Loss of ultrafiltration (UF) of peritoneal membrane is one of the most important causes of peritoneal dialysis failure. UF is determined by osmotic forces acting mainly across small pores (UFSP) and ultrasmall pores or free water transport. At present, only semiquantitative estimates or complicated computer simulations are available to assess free water transport. The aim of this study was to assess free water transport during a 3.86% peritoneal equilibration test lasting 1 hour. In this condition, sodium transport is mainly due to convection, allowing the estimate of ultrafiltration of small pores and then of free water transport (total UF - UFSP). METHODS: In 52 peritoneal dialysis patients we performed a 3.86% peritoneal equilibration test (4 hours) and a 3.86% mini-peritoneal equilibration test (1 hour) and compared UF and small solute transports obtained with the two methods. RESULTS: During the 3.86% mini-peritoneal equilibration test, UFSP and free water transport were 279 +/- 142 mL and 215 +/- 86 mL, respectively; free water transport well correlated to total UF during the 3.86% peritoneal equilibration test (r= 0.67). The groups of peritoneal transporters, categorized according to glucose dialysate ratio (D/D(0)) and to creatinine/plasma ratio (D/P(Creat)), were in good agreement for the two peritoneal equilibration tests (weighted kappa 0.62 and 0.61, respectively). CONCLUSION: The 3.86% mini-peritoneal equilibration test is a simple and fast method to assess free water transport. It also gives information about total UF and small solute transports and it is in good agreement with the 3.86% peritoneal equilibration test.     

High peritoneal residual volume decreases the efficiency of peritoneal dialysis

BACKGROUND: Wide variation in peritoneal residual volume (PRV) is a common clinical observation. High PRV has been used in both continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis to minimize the time of a dry peritoneal cavity and to achieve better dialysis. However, the impact of PRV on peritoneal transport is not well established. In this study, we investigated the effect of PRV on peritoneal transport characteristics. METHODS: Peritoneal effluents were collected in 32 male Sprague-Dawley rats after a five-hour dwell with 1.36% glucose solution. Forty-eight hours later, a four hour dwell using 25 ml of 3.86% glucose solution and frequent dialysate and blood sampling was done in each rat with 125I-albumin as a volume marker. Before the infusion of the 3.86% glucose solution, 0 (control), 3, 6, or 12 ml (8 rats in each group) of autologous effluent (serving as PRV) was infused to the peritoneal cavity. RESULTS: After subtracting the PRV, the net ultrafiltration was significantly lower in the PRV groups as compared with the control group: 13.4 +/- 0.5, 12.0 +/- 1.0, 11.7 +/- 1.7, and 8.9 +/- 0.4 ml for 0, 3, 6, and 12 ml PRV groups, respectively (P < 0.001). The lower net ultrafiltration associated with higher PRV was due to (a) a significantly lower transcapillary ultrafiltration rate (Qu) caused by a lower osmotic gradient, and (b) a significantly higher peritoneal fluid absorption rate (KE) caused by an increased intraperitoneal hydrostatic pressure. No significant differences were found in the diffusive mass transport coefficient for small solutes (glucose, urea, sodium, and potassium) and total protein, although the dialysate over plasma concentration ratios values were higher in the high-PRV groups. The sodium removal was significantly lower in the PRV groups as compared with the control group (P < 0.01). CONCLUSION: Our results suggest that a high PRV may decrease net ultrafiltration through decreasing the Qu, which is caused by a decreased dialysate osmolality, and increasing the KE caused by an increased intraperitoneal hydrostatic pressure. The high volume of PRV also decreased the solute diffusion gradient and decreased peritoneal small solute clearances, particularly for sodium. Therefore, a high PRV may compromise the efficiency of dialysis with a glucose solution.     

腹膜透析超滤衰竭的诊治策略

超滤衰竭是腹膜透析常见的并发症,是导致腹膜透析失败的重要原因之一。超滤衰竭定义为4.25%葡萄糖透析液留腹4 h后超滤量<400 ml。超滤衰竭根据病理生理机制分为4种类型：Ⅰ型超滤衰竭由于有效腹膜表面积增加导致,Ⅱ型超滤衰竭由于葡萄糖渗透转导作用下降导致,Ⅲ型超滤衰竭由于腹膜有效表面积减少导致,Ⅳ型超滤衰竭由于通过腹腔淋巴系统或局部组织间隙吸收大量水分导致。避免过度使用高浓度葡萄糖透析液、有效防治腹膜透析相关腹膜炎、保护残肾功能、选用生物相容性好的透析液、使用改善腹膜损伤和纤维化药物等是防治超滤衰竭的有益方法。     

Intraperitoneal atrial natriuretic peptide increases peritoneal fluid and solute removal

BACKGROUND: Atrial natriuretic peptide (ANP) is a hormone with well-known diuretic and vasodilating properties. Recently it was reported that ANP could increase the peritoneal fluid formation and increase peritoneal solute clearance. This study investigated the effect of ANP on peritoneal fluid and solute transport characteristics. METHODS: Eighteen male Sprague-Dawley rats were divided into three groups. A four-hour dwell study using 25 mL 2.27% glucose dialysis solution with 50 microg/kg ANP (N = 6, H-ANP) or 5 microg/kg ANP (N = 6, L-ANP) or without ANP (N = 8, control) and frequent dialysate and blood sampling was done in each rat. Radiolabeled human albumin (RISA) was added to the solution as an intraperitoneal volume marker. RESULTS: The intraperitoneal volume was significantly higher in the H-ANP group as compared with the control group and the L-ANP group. The drainage volume was 26.2 +/- 1.1, 25.5 +/- 0.7, and 29.8 +/- 0.8 mL for the control, L-ANP, and H-ANP groups, respectively (P < 0.01). This was related to significant differences in the peritoneal fluid absorption rates (K(E); estimated as the RISA elimination coefficient): 39 +/- 3, 38 +/- 3, and 19 +/- 4 microL/min, and in the direct lymphatic absorption rate (K(EB); estimated as the clearance of RISA from dialysate to blood): 7 +/- 1, 6 +/- 1, and 4 +/- 1 microL/min for the control, L-ANP, and H-ANP groups, respectively (all P < 0.01). No differences were found in the intraperitoneal volume, K(E), and K(EB) between the control group and the L-ANP group. The diffusive mass transport coefficient (K(BD)) for urea, sodium, potassium, and total protein did not differ among the three groups. However, the glucose D/D(0) was significantly higher, and the K(BD) for glucose was significantly lower in the H-ANP group as compared with the other two groups. Solute clearances (+175% for sodium and +26% for potassium) were significantly increased in the H-ANP group, mainly as a result of the increased fluid removal in this group. CONCLUSIONS: Our results suggest that ANP may decrease peritoneal fluid absorption (by 51%, partially because of decreasing the direct lymphatic absorption), resulting in a significant increase in peritoneal fluid removal and small solute clearances. While the basic diffusive permeability of the peritoneal membrane was not changed, the peritoneal glucose absorption was retarded by adding ANP to peritoneal dialysate, perhaps through interaction of ANP with glucose metabolism.