Version July 2025
INTRODUCTION —
Patients on peritoneal dialysis have a variety of peritoneal membrane transport characteristics. These differences are best classified and determined by use of the peritoneal equilibration test (PET) [1], which helps characterize the relationship between dwell time, solute diffusion, glucose absorption, drain volume, and net solute removal (see "Peritoneal equilibration test"). Those patients who have the highest rates of diffusive solute transfer typically are referred to as rapid, or high, transporters.
This topic discusses various aspects of physiology, pathophysiology, and outcomes among rapid transporters who are receiving maintenance peritoneal dialysis. Practical aspects of management that may be relevant to the care of such patients are discussed elsewhere:
●Selection of the peritoneal dialysis modality (see "Evaluating patients for chronic peritoneal dialysis and selection of modality")
●Management of hypervolemia (see "Management of hypervolemia in patients on peritoneal dialysis")
●Management of inadequate solute clearance (see "Inadequate solute clearance in peritoneal dialysis")
●Evaluation of low plasma albumin concentration (see "Nutritional status and protein intake in patients on peritoneal dialysis")
DEFINITION AND CHARACTERISTICS OF RAPID TRANSPORTERS
●Definition – Patients on peritoneal dialysis considered rapid, or high, transporters typically have a dialysate-to-plasma (D/P) creatinine ratio of >0.8 after a four-hour dwell during a peritoneal equilibration test (PET) (figure 1). However, the D/P ratio is a continuous variable with a normal distribution, and some patients with D/P creatinine ratios in the higher range but ≤0.8 (eg, 0.7) will have characteristics of rapid solute transport, as detailed below. According to PETs in different populations, approximately 15 percent of patients will be classified as rapid transporters at the start of peritoneal dialysis. (See "Peritoneal equilibration test".)
To emphasize that the movement of solutes across the peritoneal membrane occurs by passive diffusion rather than an active process, some experts have proposed replacing the term “transport” with “transfer” [2]. In such a schema, the term “rapid transport” would be replaced by “fast solute transfer rate.” Although we believe this semantic change is reasonable, the term “transport” remains commonly used in clinical practice and therefore is used in this topic review.
●Characteristics – As a result of the high rates of diffusive transport, rapid transporters transport small solutes (such as urea, creatinine, and glucose) quickly, leading to equilibration between the dialysate small-solute concentration and that of the blood relatively early in a dwell (figure 2). These patients rapidly absorb dialysate glucose, leading to early dissipation of the crystalloid osmotic gradient between dialysate and blood that is required to sustain ultrafiltration. Once the osmotic gradient is dissipated, the stimulus for ultrafiltration is gone, and ultrafiltration ceases. However, there is slow but continuous absorption of fluid via the peritoneal lymphatics, leading to poor net ultrafiltration, low drain volume, and potentially systemic volume overload. Lower drain volumes may also lead to lower solute clearance.
ETIOLOGY AND PATHOPHYSIOLOGY —
The rate of diffusion of any solute or the dialysate-to-plasma (D/P) ratio of that solute after a timed dwell is related to the number, location (distance from mesothelial surface), and perfusion of capillaries in a specified peritoneal surface area. Increased rates of diffusion can be the result of increased perfusion of existing capillaries (increased effective surface area) or an increase in the number of capillaries per unit area (an anatomic increase in capillary number/unit of surface area), both of which can be inherent or acquired.
Inherent factors — Some patients are inherently rapid transporters. This possibly is due to an associated comorbidity (where there are high levels of dialysate vascular endothelial growth factor [VEGF] or interleukin [IL]-6 [3]) or, in the absence of comorbidity, an increase in the peritoneal mesothelial cell mass (characterized by high peritoneal effluent cancer antigen 125 [CA 125] appearance rates, a surrogate for estimating mesothelial cell mass and health) [4]. Some individuals also may have a genetic predisposition: An association has been demonstrated between IL–6 gene polymorphisms and peritoneal transport [2,5,6].
Acquired factors — Peritonitis and peritoneal membrane exposure to hypertonic glucose, especially for a long duration, are associated with development of rapid peritoneal transport.
Peritonitis — Acute and chronic inflammation of the peritoneal cavity related to peritonitis can increase capillary perfusion rates and, over time, the number of capillaries per unit space. As a result, peritonitis leads to a transient increase in small-solute transport that is associated with an enhanced rate of glucose absorption and reduced ultrafiltration. This rapid and usually reversible increase in the effective peritoneal surface area most likely occurs under the influence of nitric oxide, proinflammatory cytokines (eg, IL-1 beta, tumor necrosis factor-alpha, IL-6), and prostaglandins [7]. The use of icodextrin dialysate may help preserve ultrafiltration capabilities in this setting [8]. (See "Peritoneal dialysis solutions", section on 'Glucose polymer-containing solutions (icodextrin)' and "Management of hypervolemia in patients on peritoneal dialysis", section on 'Icodextrin dialysate'.)
These changes are usually transient, but, in some patients, they persist and progress. Permanent injury to the peritoneal membrane is most common in patients on long-term peritoneal dialysis after severe episodes of peritonitis that fail to respond rapidly to treatment.
Glucose exposure — The use of hypertonic dextrose exchanges has been associated with increases in the solute transport rate [9,10]. It has been proposed that high glucose levels induce a high NADH to NAD+ ratio, which causes upregulation of hypoxia-inducible factor-1 gene and microinflammation that might be involved in the development of vasculopathy and fibrosis [11].
An accumulation of advanced glycosylation end-products in the peritoneal vessel wall also may alter peritoneal permeability. Increased immunohistochemical staining of glycosylated products appears to correlate with increased solute transport rates among patients on long-term peritoneal dialysis [12,13]. The large amount of advanced glycosylation end-products found in conventional peritoneal dialysis fluids may be the direct result of the heat sterilization process and other processes [14-17].
Long dialysis duration — Over prolonged periods, exposure to the nonphysiologic composition of dialysate (eg, low pH, high lactate) may cause morphologic and functional alterations in the peritoneal membrane that increase the solute transport rate. Bioincompatible dialysis fluid leads to significantly increased levels of circulating nitric oxide, VEGF, endothelial nitric oxide synthase, and inflammatory cytokines (IL-1 beta, tumor necrosis factor-alpha, and IL-6) that may adversely impact the peritoneal membrane [18].
TEMPORAL STABILITY OF PERITONEAL TRANSPORT —
Some patients on peritoneal dialysis are rapid transporters at the start of dialysis; others become rapid transporters as time progresses.
Increased transport over time — In many patients on peritoneal dialysis, an increase in solute transport occurs over time (figure 3) [19]. However, this change in peritoneal membrane transport usually does not prevent successful long-term peritoneal dialysis: Most patients maintain adequate solute transfer and ultrafiltration. Only a minority of rapid transporters progress to true ultrafiltration failure (also called type 1 membrane failure), which is manifest by insufficient fluid transport across the peritoneal membrane despite optimal conditions (ie, adherence, correct dialysis prescription, adequate albumin, etc). (See "Management of hypervolemia in patients on peritoneal dialysis".)
Several studies have reported increases in solute transport and decreases in ultrafiltration capacity over time. In an early study of 49 patients who underwent serial peritoneal equilibration tests (PETs) every six months, transport rates increased in 12 patients (24 percent) after 18 months [19]. In another study of 574 incident patients on peritoneal dialysis in which a standard PET was performed at least annually from 1990 to 2003, there was an increase in solute transport (ie, an increase in dialysate-to-plasma [D/P] creatinine ratio), but no decrease in ultrafiltration ability, during the first six months [10]. Subsequently, an increase in solute transport and a decrease in ultrafiltration capacity were observed. In the contemporary Global Fluid Study cohort, in 366 patients either on continuous ambulatory peritoneal dialysis (CAPD) or automated peritoneal dialysis (APD) using conventional solutions, the average transport characteristic remained the same until an increase between 3.5 and 7 years [20].
These clinical observations have been correlated with histologic examination of peritoneal membrane taken from patients undergoing peritoneal dialysis and compared with normal subjects, patients with uremia, and patients undergoing hemodialysis [21,22]. The median thickness of the submesothelial compact collagenous zone significantly increased with duration of peritoneal dialysis therapy as compared with patients with uremia and on hemodialysis. The density of blood vessels per unit length of peritoneum correlated with the degree of fibrosis suggestive of simultaneous angioneogenesis. Other significant changes included progressive subendothelial hyalinization with luminal narrowing.
Measures to stabilize membrane transport
Minimize high-glucose dialysate — The primary way of stabilizing peritoneal membrane transport characteristics is to minimize the use of hypertonic glucose dialysis solutions. This is accomplished by controlling volume excess by other means, principally as follows (see "Management of hypervolemia in patients on peritoneal dialysis"):
●Restriction of sodium intake to <2 grams/day
●Administration of loop diuretics to patients with residual kidney function
●Appropriate use of icodextrin-containing dialysate for one exchange per day, in a long dwell
●Regular laxative use in constipation-prone patients to maintain adequate peritoneal dialysis catheter outflow
Other measures — Due to lack of data or availability, other measures, such as alternative dialysis solutions, are generally not used to stabilize peritoneal membrane transport.
●Biocompatible dialysis solutions – Although a variety of alternative “biocompatible” dialysis solutions have been developed with the goal of mitigating long-term alterations to the peritoneal membrane, the evidence to support the routine use of such solutions is inconclusive [20,23,24]. Biocompatible dialysis solutions with neutral pH and low or ultralow glucose degradation products are associated with favorable effects on the peritoneal membrane in preclinical and observational studies [25,26] but demonstrate inconsistent effects in randomized controlled clinical trials [23,24]. In the Global Fluid cohort study involving both incidental and prevalent patients on peritoneal dialysis, the use of biocompatible solutions was associated with a significantly lower mean adjusted peritoneal solute transport rate (0.67 versus 0.72; p = 0.02) [20].
●Inhibition of the renin-angiotensin system – Angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) are widely used in patients on peritoneal dialysis to control blood pressure and to preserve residual kidney function. It is also possible, though by no means certain, that the use of ACE inhibitors or ARBs may help stabilize the transport characteristics of the peritoneal membrane. Peritoneal mesothelial cells have a functional local renin-angiotensin system [27]. When unregulated, this can lead to angiogenesis and fibrosis. The production of intermediary cytokines such as vascular endothelial growth factor (VEGF) and transforming growth factor-beta can be reduced with use of ACE-inhibitor or ARB therapies [28]. One retrospective, observational study correlating changes in transport over time with ACE or ARB use suggests that these agents may be protective, in that patients being administered these agents were less likely to have a change in transport over time [29].
●Peritoneal rest – Resting the peritoneal membrane by temporarily transferring the patient to hemodialysis may partially reverse functional alterations of peritoneal transport. In a study that included 35 patients on peritoneal dialysis with ultrafiltration failure, peritoneal rest was associated with a decrease in D/P creatinine ratio and an increase in ultrafiltration capacity, though only in patients who had impaired ultrafiltration for <6 months [30].
Monitoring transport characteristics — After an initial PET, we do not routinely monitor transport characteristics in patients on peritoneal dialysis; repeat PET is generally reserved for evaluating problems with ultrafiltration or solute clearance (see "Management of hypervolemia in patients on peritoneal dialysis" and "Inadequate solute clearance in peritoneal dialysis"). However, we endorse regular (eg, every three months) and standardized clinical assessments of ultrafiltration (on an overnight dwell for APD or a daytime dwell on CAPD). Barring catheter-related issues, observed decreases in ultrafiltration over time should prompt a repeat PET so that any changes in transport status may be used to optimize the dialysis prescription [2].
IMPACT ON TYPE OF PERITONEAL DIALYSIS —
Rapid transporter status generally should not dictate the selection of peritoneal dialysis modality. (See "Evaluating patients for chronic peritoneal dialysis and selection of modality".)
●Rapid transport and selection of peritoneal dialysis modality – We believe that most patients should choose either continuous ambulatory peritoneal dialysis (CAPD) or a type of automated peritoneal dialysis (APD; usually continuous cycler peritoneal dialysis [CCPD]) based upon their preferences and lifestyle rather than on the transport characteristics of their peritoneal membrane. Rapid transporters usually can dialyze successfully with either modality provided the nephrologist is willing to individualize the patient's prescription. This is especially true in patients who have residual kidney function, which makes it easier to maintain euvolemia and solute removal.
However, if one were to design a peritoneal dialysis prescription based solely upon transport characteristics, attempting to optimize ultrafiltration, drain volumes, and creatinine clearance, rapid transporters would do best with short dwell times (1.5 to 3 hours/dwell). If using only glucose-containing solutions, such patients in theory would do best with APD modalities, such as nightly intermittent peritoneal dialysis (NIPD; a modification of CCPD in which patients do not utilize a daytime dwell) or nightly CCPD with a last-bag fill (first morning fill) and a midday exchange. By contrast, low-average or low transporters would do best with prolonged dwells, such as those associated with CAPD or CCPD with fewer overnight exchanges.
NIPD is typically reserved for patients who are just starting dialysis and have significant residual kidney function (see "Evaluating patients for chronic peritoneal dialysis and selection of modality"). This is because the removal of larger solutes (called middle molecules), such as beta-2 microglobulin, is dwell-time dependent even among patients with rapid transporter characteristics. Thus, even though rapid transporters could likely meet their small solute removal (Kt/V urea) targets with NIPD alone (ie, without a daytime dwell), patients with very low residual kidney function or anuria require the addition of a long dwell to optimize the removal of middle molecules. In such patients, the use of icodextrin typically permits a long dwell without negative ultrafiltration.
●Outcomes data – Our approach to prioritizing patient preference when selecting peritoneal dialysis modality is supported by most outcome studies comparing CAPD with APD. In an observational study of 42,942 patients on CAPD and 23,439 on APD in the United States who started peritoneal dialysis during the years 1996 to 2004 and were followed through September 2006, peritoneal dialysis modality was not associated with survival [31]. Although there was no adjustment for transport status in this study, another study of patients on peritoneal dialysis in Australia and New Zealand did adjust for transport type and also reported no demonstrable difference in risk of death for CAPD or APD [32]. By contrast, an analysis of a cohort of patients on peritoneal dialysis in Australia and New Zealand reported a lower risk of death in high transporters treated with APD compared with those on CAPD [33].
PATIENTS WITH MALNUTRITION —
The relationship between rapid transporter status and protein malnutrition is discussed below. The approach to nutrition and protein intake for all patients on peritoneal dialysis, regardless of transport status, is addressed separately. (See "Nutritional status and protein intake in patients on peritoneal dialysis".)
Rapid transport and low albumin — Most patients with high rates of peritoneal transport will have a tendency for hypoalbuminemia, and some will actually be malnourished. Cross-sectional data from patients undergoing continuous ambulatory peritoneal dialysis (CAPD) have shown an inverse correlation between peritoneal transport characteristics (as estimated from the four-hour dialysate-to-plasma [D/P] creatinine ratio) and the plasma albumin concentration [34]. This relationship tends to be independent of dialysis dose, and hypoalbuminemia is typically accompanied by other signs of malnutrition [35]. The association of higher creatinine transfer rates with hypoalbuminemia and malnutrition is probably related to enhanced dialysate protein losses, which can be as high as 15 g/day; in comparison, the mean for all patients on CAPD is approximately 6 g/day. Another explanation is that the high-transport status is caused by chronic inflammation, which itself is associated with low serum albumin concentration.
There are probably other factors that contribute to the tendency toward malnutrition in rapid transporters. As an example, patients on long dwells often require hypertonic glucose dialysis solutions to achieve net ultrafiltration and maintain euvolemia. It is possible that the increased glucose load may suppress appetite [36]. Another possibility is that these patients tend to be slightly volume expanded and are hypoalbuminemic in part due to dilution [37].
Short-dwell dialysis preferred — In addition to the same evaluation of and treatment for protein malnutrition as other patients on peritoneal dialysis (see "Nutritional status and protein intake in patients on peritoneal dialysis"), malnourished patients with rapid transporter characteristics should receive short-dwell dialysis (eg, nightly intermittent peritoneal dialysis [NIPD] or continuous cycler peritoneal dialysis [CCPD]) rather than CAPD to minimize dialysate protein losses. A putative advantage of NIPD in rapid transporters is that the abdomen is dry during the day, thereby minimizing some of the protein losses [38], although not all studies have confirmed this [39,40]. However, if possible, icodextrin should be used for a long daytime dwell. This will minimize glucose absorption, possible appetite suppression, and excessive fluid absorption while maintaining 24-hour dialysate clearances of substances such as middle molecules. Some patients with rapid transporter characteristics may need a trial of hemodialysis to see if the malnutrition improves.
One early study showed that rapid transporters treated with NIPD have a lower rate of dialysate protein loss and a lesser need for hypertonic dialysate solutions [38], whereas other studies showed protein losses to be similar in all types of peritoneal dialysis therapies [39,40]. If the dialysis dose is adequate, then the reductions in protein loss and glucose absorption should permit an increase in energy intake and at least partial correction of the malnourished state. Among the benefits noted in a study of patients initially switched from CAPD to NIPD were [38]:
●A rise in the plasma albumin concentration from 3.40 to 3.49 g/dL
●An elevation in protein catabolic rate, an estimate of protein intake, from 0.54 to 0.57 g/kg per day
●A reduction in dialysate protein losses from 6.76 to 5.39 g/day
The lack of normalization of the plasma albumin concentration in this setting may be related to persistent dialysate protein losses, volume overload if the patient’s volume status is not well managed on NIPD (dry days), or inadequate dialysis. If the patient is malnourished and not doing well, a higher than minimal Kt/V may be needed.
RAPID TRANSPORT AND MORTALITY —
Contemporary data suggest that associations between rapid transporter status and increased mortality, if observed, are likely due to suboptimal management of the dialysis prescription in such patients or to underlying comorbidities and inflammation that underlie the rapid transport state. We believe that rapid transporters can be managed on peritoneal dialysis without an excess mortality risk provided their therapy is appropriately individualized [41].
Historical cohort studies suggested that rapid transport status predicted increased mortality among patients on peritoneal dialysis [42-45]. These data were summarized in a 2006 meta-analysis, which reported that for every 0.1 increase in the dialysate-to-plasma (D/P) creatinine ratio value, there was an increase in the relative risk of death of 1.15 (95% CI 1.07-1.23) [45]. Most of the deaths were cardiovascular in nature. Postulated mechanisms included fluid overload causing uncontrolled hypertension and left ventricular hypertrophy, malnutrition, increased protein losses, and chronic inflammation [46,47].
However, the 2006 meta-analysis discussed above predominantly included patients on continuous ambulatory peritoneal dialysis (CAPD), a therapy in which rapid transporters would be predicted to do poorly with ultrafiltration. In subsequent studies, conducted in a period when clinicians began to pay more attention to individualizing the peritoneal dialysis prescription for rapid transporters by shortening dwell times, transferring to automated peritoneal dialysis (APD), or using icodextrin for long dwells, transport status was not associated with risk of death [48-51].
The survival improvement in rapid transporters in later time periods is illustrated by an observational study comparing mortality in patients who started peritoneal dialysis between 1990 and 1997 with that of patients who started peritoneal dialysis between 1998 and 2005 [49]. In the earlier but not later period, rapid peritoneal transport status predicted the risk of death (figure 4). Similarly, in the Global Fluid Study, where data on 959 patients from 10 centers in the United Kingdom, South Korea, and Canada were evaluated, higher transport was associated with increased mortality in prevalent but not incident patients [5].
SOCIETY GUIDELINE LINKS —
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Dialysis".)
INFORMATION FOR PATIENTS —
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Peritoneal dialysis (The Basics)")
●Beyond the Basics topic (see "Patient education: Peritoneal dialysis (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Definitions and characteristics – Patients considered rapid, or high, transporters typically have a dialysate-to-plasma (D/P) creatinine ratio of >0.8 after a four-hour dwell during a peritoneal equilibration test (PET) (figure 1). As a result of high rates of diffusive transport, rapid transporters transport small solutes quickly, leading to equilibration between the dialysate small-solute concentration and that of the blood early in a dwell. Such patients tend to have poor net ultrafiltration and low drain volume (figure 2), which may require modification of the peritoneal dialysis prescription to avoid volume overload and inadequate solute clearance. (See 'Definition and characteristics of rapid transporters' above and "Peritoneal equilibration test".)
●Etiology – Some patients are inherently rapid transporters. Other patients become rapid transporters over time due to repeated episodes of peritonitis or long-term exposure to hypertonic dextrose exchanges. (See 'Etiology and pathophysiology' above.)
●Stabilizing peritoneal membrane transport over time – The primary way of stabilizing peritoneal membrane transport is to minimize the use of hypertonic dextrose dialysis solutions. This is accomplished by controlling volume excess by other means, principally as follows (see 'Measures to stabilize membrane transport' above):
•Restriction of sodium intake to <2 grams/day
•Administration of loop diuretics to patients with residual kidney function
•Appropriate use of icodextrin-containing dialysate for one exchange per day, in a long dwell
•Regular laxative use in constipation-prone patients to maintain adequate peritoneal dialysis catheter outflow
The interventions above are detailed elsewhere. (See "Management of hypervolemia in patients on peritoneal dialysis".)
●Impact on peritoneal dialysis modality – Most patients should choose either continuous ambulatory peritoneal dialysis (CAPD) or a type of automated peritoneal dialysis (APD; usually continuous cycler peritoneal dialysis [CCPD]) based upon their preferences and lifestyle rather than on the transport characteristics of their peritoneal membrane. Rapid transporters usually can dialyze successfully with either modality provided the nephrologist is willing to individualize the patient's prescription. However, if one were to design a peritoneal dialysis prescription based solely upon transport characteristics, rapid transporters would do best with the short dwell times of APD. (See 'Impact on type of peritoneal dialysis' above and "Evaluating patients for chronic peritoneal dialysis and selection of modality".)
●Patients with malnutrition – Most patients with high rates of peritoneal transport will have a tendency for hypoalbuminemia, and some will actually be malnourished. For malnourished patients on peritoneal dialysis who have rapid transporter characteristics, we suggest short-dwell dialysis (eg, CCPD) rather than CAPD (Grade 2C). Although the mainstays of malnutrition treatment are nutritionist intervention, adherence to the prescribed dialysis regimen, and identification and treatment of comorbid disease, short-dwell dialysis minimizes dialysate protein losses. (See 'Patients with malnutrition' above and "Nutritional status and protein intake in patients on peritoneal dialysis".)
●Rapid transport and mortality – Rapid transporters can be managed on peritoneal dialysis without an excess mortality risk provided their therapy is appropriately individualized. (See 'Rapid transport and mortality' above.)
