Solute transport in continuous hemodialysis: a new treatment for acute renal failure

A pumpless dialysis technique which combines continuous convection and diffusion was studied in 15 critically ill acute renal failure patients. Fluid identical in composition and purity to that used in peritoneal dialysis was continuously circulated (single-pass) at 16.6 cc/min through the dialysis compartment of a 0.43 m2 flat plate PAN membrane dialyzer. Whole blood clearances for urea, creatinine and phosphate averaged 25.3 +/- 4.4 cc/min, 24.1 +/- 5.5 cc/min and 21.3 +/- 5.6 cc/min, respectively. Over the range of blood flows studied (50 to 190 cc/min) clearances of these solutes were independent of blood flow rate but rather were determined by both dialysate flow rate and ultrafiltration rate. In contrast net fluxes of calcium and sodium were correlated only with ultrafiltration rate. Bicarbonate loss was 0.52 +/- 0.11 mEq/min; K+ balance varied with dialysate K+; glucose uptake from dialysate was 107 +/- 24.0 mg/min. In fresh non-clotting dialyzers, mean ultrafiltration rate was 8.1 cc/min. At QBi of 70 to 190 cc/min, dialysate and blood solute equilibrate yielding a total clearance equal to the dialysate outflow, or 25 cc/min, that is, the sum of dialysate flow rate plus ultrafiltration rate. In comparison to currently used continuous arteriovenous hemofiltration (CAVH), the exceptionally-high solute clearances obtained with continuous hemodialysis constitute a significant improvement in continuous renal replacement therapy.     

Current concepts in peritoneal dialysis

Peritoneal dialysis has been increasingly employed to treat patients with end-stage renal failure. Solute transport can be enhanced by increasing ultrafiltration with hypertonic dialysate, infusing intraperitoneal vasodilators to increase the effective surface area for exchange, and by employing new methods of dialysate delivery which may improve dialysate mixing and decrease the effective membrane resistance to solute flux. While infection remains a major complication of peritoneal dialysis, techniques to prevent and treat infections have been effectively employed. Progress has also been made in the treatment of diabetic patients with peritoneal dialysis. Continuous ambulatory peritoneal dialysis, a relatively new technique with fast growing clinical application, may be the therapy of choice for many patients with end-stage renal failure.     

The role of tidal peritoneal dialysis in modern practice: A European perspective

Tidal peritoneal dialysis (TPD) has been introduced to optimize adequacy of peritoneal dialysis (PD). Early studies reported similar or even better small solute clearances with TPD than those achieved with continuous ambulatory peritoneal dialysis or continuous cyclic peritoneal dialysis. However, in many studies treatment volumes were much higher during TPD compared with other PD modalities. Based on current evidence, TPD provides no advantage of increased small solute clearances, middle molecule clearances, or peritoneal ultrafiltration as compared to non-tidal automated peritoneal dialysis (APD) when dialysate flow is kept constant. However, TPD reduces drainage pain and nightly alarms during cycler treatment. Tidal volume should be kept as high as possible in these patients, especially in those with low average peritoneal transport rates. Based on theoretical considerations and little evidence, TPD could provide better clearances than conventional APD when a very high dialysate flow (>or=5 l/h) is used. Such dialysate flow rates are not routinely prescribed in home APD patients. However, they may be interesting for in-center PD patients. One randomized crossover trial reported higher small solute clearances with TPD compared to non-tidal APD in patients with acute renal failure. TPD is also the preferred treatment modality in patients with ascites as it allows a controlled outflow of fluid from the peritoneal cavity. Newer treatment modalities, for example, continuous flow PD, may be interesting alternatives in an effort to increase efficacy of PD in the future. However, because such treatment regimens are expensive and elaborate they have not been established for routine use until now.     

Dialysate flow rate and peritoneal clearance

We evaluated the influence of dialysate flow rates upon peritoneal clearance of urea, creatine, protein losses into dialysate, glucose disappearance from dialysate, sodium removal from the patient during dialysis, and ultrafiltration rate in 64 patients undergoing intermittent peritoneal dialysis. We evaluated three dialysate flow rates: 2 L/h, 3 L/h, and 4 L/h. All dialysate contained 1.5% glucose. The clearance of urea in milliliters per minute (2-L series 14.0, 3-L series 15.1, 4-L series 17.6) and creatinine in milliliters per minute (2-L series 9.3, 3-L series 10.6, 4-L series 11.6) determined at a dialysate flow rate of 4 L/h was significantly greater than the clearances determined at 3 and 2 L/h of dialysate flow (P less than 0.05). The clearance of glucose from the peritoneal cavity in milliliters per minute (2-L series 6.9, 3-L series 7.9, 4-L series 8.9) was significantly greater for the 4-L series as compared with the 2-L series (P less than 0.05). There were no other significant differences. Neither sex, race, previous episodes of peritonitis, nor etiology of renal failure influenced the results. Given the high cost of dialysate, we recommend dialysate flows of 2 L/h if a patient has a residual renal clearance of 2.5 mL/min. Although increasing dialysate flow rate may compensate for renal clearances significantly less than this, we believe the patient should be offered hemodialysis, continuous cyclic peritoneal dialysis (CCPD), or continuous ambulatory peritoneal dialysis (CAPD).     

Net Ultrafiltration May Not Eliminate Backfiltration During Hemodialysis with Highly Permeable Membranes

Backfiltration of dialysis solution can occur during hemodialysis with highly permeable membranes. A method has recently been developed for determining backfiltration rates in vitro at low dialysate flow rates by measuring changes in the local dialysate concentration of a marker macromolecule via sampling ports added to the hemodialyzer housing. In the present study, the influence of net ultrafiltration on backfiltration rates was determined for five commercial dialyzers containing membranes with different water permeabilities. In vitro experiments were performed (n = 3) using freshly donated whole blood at blood flow rates of 200 and 340 ml/min and at a dialysate flow rate of 100 ml/min. At zero net ultrafiltration, backfiltration rates increased with increasing membrane water permeability and ranged from 0.9 to 6.9 ml/min. At a net ultrafiltration rate of 10 ml/min, backfiltration was eliminated for dialyzers containing membranes with water permeabilities of less than 30 ml/h/mm Hg but remained significant for dialyzers with higher membrane water permeabilities. Therefore, despite a significant net ultrafiltration rate, backfiltration may still occur during hemodialysis with highly permeable membranes.     

Continuous flow peritoneal dialysis: principles and applications

Continuous flow peritoneal dialysis (CFPD) is a technique of renal replacement therapy (RRT) dating back to the 1960s. Its essential features are a fixed intraperitoneal volume and rapid, continuous movement of dialysis solution into and out of the peritoneal cavity. Inlet and outlet catheters and a means of generating a large volume of sterile dialysate are required. External regeneration of dialysate via conventional hemodialysis (HD) equipment or sorbent technology mitigates the need for large volumes of sterile fluid and makes the technique feasible. Clearance depends on the peritoneal mass transfer coefficient, rate of dialysate flow, and efficiency of external regeneration. Studies to date all demonstrate small solute clearances three to eight times greater than conventional automated peritoneal dialysis (PD). Catheter design is crucial to the clinical success of the technique and will be discussed. Potential applications include daily home dialysis, treatment of acute renal failure in the intensive care unit (ICU), and ultrafiltration of ascites. Clinical experience with the latter will be presented in detail.     

一氧化氮及其抑制剂对大鼠腹膜通透性的作用

目的 研究一氧化氮(NO)及一氧化氮抑制剂(L-NMMA)对腹膜透析通透性,特别是高糖透析中的作用。方法 建立大鼠长期腹膜透析模型,测定不同浓度透析液中以及不同刺激条件下腹膜巨噬细胞产生NO的水平。分别用1.5％、4.25％的葡萄糖透析液及分别加L-NMMA(5mg·kg~(-1)·d~(-1))行SD大鼠透析。10d后测定其腹膜动力学的变化。结果 腹膜巨噬细胞产生NO的水平,4.25％的葡萄糖透析液高于1.5％葡萄糖透析液(P<0.01),而后者又高于生理盐水(P<0.01)。高糖透析可减少腹膜的液体超滤(P<0.05)及溶质的转运。加用L-NMMA后腹膜的液体超滤及溶质的转运增加(P<0.05)。结论 腹膜透析时腹腔产生NO的水平增高,对腹膜的通透性增高中起一定作用。透析液中加入L-NMMA可改善腹膜的通透性。     

Feasibility of resuming peritoneal dialysis after severe peritonitis and Tenckhoff catheter removal

Published guidelines suggest that after an episode of severe peritonitis that requires Tenckhoff catheter removal, peritoneal dialysis can be resumed after a minimum of 3 wk. However, the feasibility of resuming peritoneal dialysis after Tenckhoff catheter removal remains unknown. One hundred patients were identified with peritonitis that did not respond to standard antibiotic therapy in a specific center. Their clinical course was reviewed; in all of them, Tenckhoff catheters were removed and reinsertion was attempted at least 4 wk later. In 51 patients, the Tenckhoff catheter was successfully reinserted and peritoneal dialysis was resumed (success group). In the other 49 patients, reinsertion failed and the patient was put on long-term hemodialysis (fail group). The patients were followed for 18.5 +/- 16.8 mo. The overall technique survival was 30.8% at 24 mo. In the success group, 11 patients were changed to long-term hemodialysis within 8 mo after their return to continuous ambulatory peritoneal dialysis. In the fail group, 18 of the 20 deaths occurred within 12 mo after conversion to long-term hemodialysis. After resuming peritoneal dialysis, there was a significant decline in net ultrafiltration volume (0.38 +/- 0.16 to 0.21 +/- 0.19 L; P = 0.03) and a trend of rise in dialysate-to-plasma ratios of creatinine at 4 h (0.664 +/- 0.095 to 0.725 +/- 0.095; P = 0.15). Forty-five patients (88.2%) required additional dialysis exchanges or hypertonic dialysate to compensate for the loss of solute clearance or ultrafiltration, although there was no significant change in dialysis adequacy or nutritional status. It was concluded that after an episode of severe peritonitis that required Tenckhoff catheter removal, only a small group of patients could return to peritoneal dialysis. An early assessment of peritoneal function after Tenckhoff catheter reinsertion may be valuable.     

Estimation of Mass Transfer Through a Hemodialyzer: Theoretical Approach and Clinical Applications

Abstract: The estimation of the solute mass transfer through a dialyzer is generally based on the solute dialysance, but the concept of dialysance has been precisely defined only in the case of a merely diffusive transfer. In actuality the mass transfer of a solute is also influenced by the ultrafiltration responsible for a convective transfer and, if the solute is an ionic substance, by the transmembrane gradient of electrical potential due to the Gibbs-Donnan effect. The aim of this paper is to generalize the concept of dialysance when the diffusive, convective, and electric components of the transfer are simultaneously active. There are at least 3 modes to generalize the concept of dialysance for it to be identical, when the amount of ultrafiltration and the Gibbs-Donnan effect are negligible, to the usual dialysance defined in the case of a merely diffusive transfer. The dialysance can be defined so that it can be equal to the clearance for a solute absent from the dialysate again, so that it still represents the rate at which the plasma concentration of a given solute is reaching its equilibrium value, or so that it represents the merely diffusive component (independent of the ultrafiltration rate) of the mass transfer. This generalized concept of dialysance can be useful to provide a real-time estimation of the effective dialysis dose actually delivered to the patient; to automatically optimize, by a biofeedback process, the sodium balance during a hemodialysis session; and to adapt dialysate concentrations for new hemodialysis techniques with convective transfer (acetate-free biofiltration).     

Adequacy of automated peritoneal dialysis with and without manual daytime exchange: A randomized controlled trial

Until now, it remains unclear whether the addition of manual daytime exchanges or increasing the nightly dialysate flow is the best strategy to optimize automated peritoneal dialysis (APD) treatment. In this open-label randomized controlled crossover trial, 18 patients with high-average (HA) or low-average (LA) peritoneal transport rates sequentially underwent two different APD regimens for 7 days each, with an intermittent washout period of 7 days. 'Manual exchange' treatment was a conventional APD with low nightly dialysate flow and one manual daytime exchange. 'High-flow' treatment was defined by cycler therapy with high dialysate flow but without manual daytime exchange. Creatinine clearances (8.56+/-1.22 vs 7.87+/-1.04 l/treatment, P = 0.011) and urea nitrogen clearances (12.83+/-1.98 vs 11.68+/-1.06 l/treatment, P = 0.014) were significantly increased during 'high-flow' treatment compared to 'manual exchange' treatment. Sodium removal was significantly lower and glucose absorption was higher with the 'high-flow' regimen. Phosphate clearances, beta2-microglobulin clearances, ultrafiltration, and peritoneal protein loss were not different between the two treatment modalities. Subgroup analysis dependent on peritoneal transport types showed that the effect on clearances was most marked and significant in HA transporters, whereas sodium removal was lowest in LA transporters. We conclude that small solute clearances can be significantly improved and middle molecule clearances maintained in APD patients by increasing the nightly dialysate flow instead of adding a manual daytime exchange. However, the possible benefit of better clearances with higher nightly treatment volumes has to be weighed against increased costs and the possible negative impact of impaired sodium removal, especially in LA transporters.     

The simulation of continuous arteriovenous hemodialysis with a mathematical model

We have developed a mathematical model that predicts the performance of continuous arteriovenous hemodialysis. Given patient (plasma protein concentration, hematocrit, mean arterial pressure, central venous pressure) and circuit (flow resistance, membrane hydraulic permeability, dialyzer mass transfer coefficient, ultrafiltrate column height, dialysate flow rate) characteristics as inputs, predictions of hydraulic and oncotic pressure distribution, filtration rate, blood flow, total, diffusive, and convective urea clearances are provided. The model was tested by perfusing a circuit with bovine blood under conditions of pure ultrafiltration, zero net ultrafiltration and dialysis, or combined ultrafiltration and dialysis (countercurrent dialysate flow at rates of 10, 20, and 30 ml/min). In order to permit computation, membrane hydraulic permeability and flow resistances were measured. Dialyzer mass transfer coefficient for urea could not be measured directly and so was determined by fitting model predictions to measured urea clearances. For all conditions of operation, a urea mass transfer coefficient of 0.014 cm/min successfully simulated the data. Predictions of blood flow, filtrate generation rate, and circuit pressure distribution were accurate. At lower dialysate flow rates, urea clearance approximated the sum of dialysate flow and filtration rate. At higher dialysate flows, however, departure from this ideal blood-dialysate equilibrium was observed. Model predictions regarding the relative contributions of diffusion and convection to urea clearance were explored. Under conditions of nearly perfect equilibration of urea between blood and dialysate at the blood inlet, the model predicts that the diffusive clearance of urea will increase with increasing rate of filtration and may exceed the rate of dialysate inflow.     

Definitions of Differences and Changes in Peritoneal Membrane Water Transport Properties

A survey is given comparing measurements of transperitoneal water transport in different clinical situations with analyses based on the so-called "pore theory." This model links the measured changes to physical alterations of the peritoneal membrane. The calculations include "equivalent pore radius," effective "membrane area" and diffusive length, the transport resistance of the unstirred dialysate layer, and the residual intraperitoneal volume after dialysate drainage. The clinical appearances include individual differences in transperitoneal transport characteristics, changes in transperitoneal transport over time on continuous ambulatory peritoneal dialysis (CAPD) and during peritonitis, the pharmacological effect on the transport properties, and the effect of peritoneal catheter dislocation on ultrafiltration capacity. The main conclusions are as follow: During CAPD treatment the measurement of intraperitoneal solute equilibration and "mass-transfer-area coefficients" for urea and creatinine is less sensitive than the measurement of ultrafiltration volume in revealing peritoneal membrane changes. Differences and changes found have mostly a combined physical explanation, but one is more or less dominant. Changes in peritoneal membrane area seem to be the most dominant cause of changes in transperitoneal transport during time on CAPD and when sodium nitroprusside was added to the peritoneal dialysate. Changes during peritonitis can be explained by changes in pore radius and depth. Individual differences can be explained by differences in "membrane" area and in resistance of the unstirred dialysate fluid. High residual dialysate volume can give rise to clinical problems and should be considered when placing the catheter in the peritoneal cavity.     

Peritoneal dialysis, membranes and beyond

PURPOSE OF REVIEW: The peritoneal membrane provides the interface between dialysate fluid and blood for peritoneal dialysis patients. Functional properties of the peritoneal membrane have important clinical implications. This review will outline recent observations concerning structural changes in the peritoneal membrane and the impact on function and clinical outcomes. RECENT FINDINGS: Peritoneal membrane function - solute transport and ultrafiltration - is a complex process involving new blood vessel growth along with changes in the nature of blood vessels and the interstitial environment of these vessels. Advanced glycation end-products produced by reactive oxygen species in the dialysis fluid have been identified as an agent of tissue fibrosis. Nitric oxide and IL-6 also have important roles in peritoneal membrane injury. Gene polymorphisms associated with peritoneal membrane function have been identified. As the mechanisms of peritoneal membrane injury become better elucidated, targeted therapies are being developed. The role of biocompatible and nonglucose dialysis fluids needs to be further defined. SUMMARY: The peritoneal membrane is the lifeline for peritoneal dialysis patients. Our understanding of mechanisms of injury and functional responses continues to expand and will hopefully lead to therapies to improve the clinical outcomes for peritoneal dialysis patients.     

Dialysate cancer antigen 125 in long-term peritoneal dialysis patients

Structural and functional peritoneal membrane changes are associated with long-term peritoneal dialysis. These changes can lead to ultrafiltration failure and peritoneal fibrosis, reducing the efficacy of the peritoneal membrane to remove waste and balance fluid and electrolytes. The loss of mesothelial cells from the basement membrane is one of the major characteristics in peritoneal membrane structural change. Thus, if the reduction of peritoneal mesothelial cell mass in peritoneal dialysis patients is monitored, signs of ultrafiltration failure and peritoneal fibrosis can be detected early. One of biomarkers that can be used to indicate the change in peritoneal mesothelial cell mass is CA125, which is produced by mesothelial cells. In this article, we review the measurement and clinical use of CA125 in peritoneal dialysate effluent. Additionally, we address the data and studies on the association between dialysate CA125 levels and factors related to ultrafiltration failure and peritoneal fibrosis, including the parameters used to monitor the functional status of the peritoneal membrane. Our review shows that dialysate CA125 can be used to evaluate the peritoneal membrane in noninfected patients to predict peritoneal fibrosis, and it can also be used as a biomarker of biocompatible dialysis solutions.     

Recirculation peritoneal dialysis with sorbent Redy cartridge.

Sorbent regeneration of peritoneal dialysate and use of small volume of dialysate for intermittent peritoneal dialysis (IPD) has been shown to be feasible. The present study compares the solute clearance (C) for urea (U) and creatinine (Cr) at varying flow rates in IPD and in recirculation peritoneal dialysis (RPD) utilizing Redy cartridge in ten dogs. Two silastic peritoneal catheters and one Sarns roller pump were used for RPD. CU was 12 +/- 2 ml/min (mean +/- 1SD),18 +/- 2 with IPD and 15 +/- 2,21 +/- 4 with RPD at flow rate of 66 and 100 ml/min, respectively, while CCr was 9 +/- 2,12 +/- 2 with IPD and 10 +/- 2, 13 +/- 3 with RPD. At increasing flow rates of 150,200 and 250 ml/min, CU was 27 +/- 3,31 +/- 4 and 32 +/- 6, and CCr was 17 +/- 2,20 +/- 3 and 22 +/- 3 with RPD. U and Cr were completely removed by the Redy. Glucose was not removed by the cartridge after initial saturation. Serum sodium concentration increased 2-3 mEq/l after 6 h of RPD. The data suggest that at comparable flow rates, RPD is relatively more efficient than IPD (p greater than 0.01). This may be due to continuous exchange across the peritoneal membrane in RPD. At high flow rate in RPD, solute removal is 2-3 times higher than the currently used IPD. RPD with Redy cartridge is mechanically simple, efficient, and may help reduce total peritoneal dialysis time.     

A peritoneal-based automated wearable artificial kidney

Work on wearable kidneys has evolved around the technology of hemodialysis or hemofiltration, which call for continuous anticoagulation of the extracoporeal circulation and are encumbered with potential immunologic and non-immunologic complications of continuous blood-artificial membrane interactions. A peritoneal-based automated wearable artificial kidney (AWAK) requires no extracorporeal circulation and is therefore "bloodless." Because AWAK is designed to continuously regenerate and reuse the spent dialysate in perpetuity, it is also "waterless." A sorbent-based assembly regenerates both the aqueous and the protein components (AqC and PrC) of the spent dialysate, producing a novel, autologous protein-containing dialysate. The regenerated AqC has the same composition as the commercially available peritoneal dialysate, but contains bicarbonate instead of lactate and has a more physiological pH. The regenerated PrC is recycled back into the peritoneal cavity, thereby ameliorating or eliminating protein loss. Depending on the steady-state protein concentrations that can be achieved (under the condition of continuous dialysate regeneration and recycling), the PrC also has the potential of both augmenting ultrafiltration and mediating the removal of protein-bound toxins. Additional sorbents can be incorporated into AWAK for the removal of middle molecular weight uremic toxins. At a regeneration rate of 4 l/h, AWAK provides a dialysate flow of 96 l/day (8-12 times the current rate). Round-the-clock dialysis and ultrafiltration provide steady-state metabolic-biochemical and fluid balance regulation, thereby eliminating "shocks" of abrupt changes in these parameters that characterize the current dialytic modalities. Dialysis-on-the-go, made possible by AWAK's "wearability" and automation, frees end-stage renal failure patients from the servitude that is demanded by the current dialytic regimentations.     

Kinetic Modeling of Continuous Flow Peritoneal Dialysis

Kinetic models have been derived for analysis of the effects on peritoneal urea clearance ( K _p) of continuous single-pass flow of fresh peritoneal dialysate and continuous flow of peritoneal dialysate recirculating through an external dialyzer. Generalized solution of the models shows that both predict K _p to be a well-defined function of the peritoneal mass transfer coefficient (MTC) and the dialysance ( D ) of the external dialyzer, while the MTC is a function of the rate and distribution of dialysate flow. Thus the models should be useful to guide studies to optimize CFPD. Analysis of reported in vivo data indicate that with dialysate flow rate and D both in the range of 200 ml/min, MTC levels of 60–70 ml/min and K _p levels of 50 ml/min can be achieved. If the model predictions are verified in vivo, 8-hour overnight CFPD 6 nights/week could provide the average-size anephric patient a weekly stdKt / V of 3.2 which is competitive with daily hemodialysis. Kinetic modeling of ultrafiltration indicated ultrafiltration rates 0.2–0.3 L/hr should be achieved with 1.0–1.25% dextrose dialysate. The model shows average rates of glucose absorption can theoretically be reduced by 33% compared to CAPD with the same amount of fluid removal.     

Acute peritoneal dialysis as both cause and treatment of hypernatremia in an infant

This report describes a 4-month-old infant with multisystem organ failure who developed severe hypernatremia (sodium 168 mEq/l) due to rapid free water removal associated with acute peritoneal dialysis instituted for fluid overload. The current report describes the pathophysiology of the hypernatremia, and its correction by low-sodium hypertonic peritoneal dialysis without compromising ultrafiltration or supplementing with free water. Although peritoneal dialysis can cause hypernatremia, a modified solute concentration in the dialysate can treat the hypernatremia successfully. Received: 2 January 2001 / Revised: 24 April 2001 / Accepted: 24 April 2001