Inadequate solute clearance in peritoneal dialysis

INTRODUCTION — The goal of peritoneal dialysis is to remove solutes and fluid that are usually excreted by the kidney. This removal of solutes is achieved by diffusion (solute movement down a concentration gradient) and convection (solute movement that accompanies ultrafiltration). Occasionally, the dialysis procedure does not remove sufficient solute or fluid, eventually causing uremia and volume overload.

It is important to note that "adequate dialysis" can be defined in many ways. Societal guidelines often define adequacy in terms of total solute removal (by dialysis and residual kidney function) or that by dialysis alone (which is more common when considering hemodialysis). Adequate dialysis may be defined numerically in terms of solute removal or clinically by evaluation of patients' symptoms and well-being. At times, one may want to prescribe "high-quality goal-directed dialysis" and not necessarily meet all societal or governmental "numerical" or "laboratory recommendations" of adequacy [1].

This topic reviews factors that contribute to inadequate measured solute removal among peritoneal dialysis patients and provides an approach to the management of such patients.

The discussion assumes that the measured solute removal was initially adequate and that solute removal has become impaired over time. A review of the factors that must be considered at the initiation of dialysis is presented separately. (See "Evaluating patients for chronic peritoneal dialysis and selection of modality".)

The management of peritoneal dialysis patients with ultrafiltration failure and volume overload is discussed elsewhere. (See "Management of hypervolemia in patients on peritoneal dialysis".)

The factors that regulate solute and water transport across the peritoneal membrane are discussed separately. (See "Mechanisms of solute clearance and ultrafiltration in peritoneal dialysis".)

DEFINITIONS OF TERMS — The following terms are commonly used to define problems associated with dialysis adequacy of solute removal.

Solute clearance — Solute clearance is the volume of blood (as opposed to plasma) that is cleared of a substance over a unit of time (ie, in mL/min, L/day, or L/week). Total solute clearance refers to the clearance provided by both dialysis and the small amount of remaining native kidney function (termed residual kidney function), if any. The blood urea nitrogen (BUN) and serum creatinine are commonly used as markers for total solute clearance in peritoneal dialysis patients. A progressive increase in the BUN or plasma creatinine concentration suggests that solute clearance has decreased, although progressive increases may also be caused by increased production of either substance. (See 'Causes of increased BUN' below.)

Two metrics are commonly used to measure solute clearance by peritoneal dialysis. These include the weekly Kt/Vurea and the creatinine clearance normalized to body surface area [2]. We use the total (peritoneal dialysis and residual kidney function) weekly Kt/Vurea, which is consistent with the 2006 Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines, the 2005 European Best Practices Guidelines (EBPG), and the 2006 International Society for Peritoneal Dialysis (ISPD) guidelines/recommendations [3-5].

The daily peritoneal urea clearance (Kt) is the product of the total 24-hour peritoneal drain volume and the ratio of the urea concentration in the pooled drained dialysate to that in the plasma (D/P urea). The volume of distribution of urea (Vurea) is approximately equal to body water (ie, approximately 60 percent of ideal body weight in kg in men and 55 percent of ideal body weight in kg in women).

We use a 24-hour urea clearance to determine residual kidney function. The 24-hour urea clearance is calculated as follows:

Urea clearance in mL/min x 1400 min provides the urea clearance per day.

Total solute removal — Total solute removal is defined as the total amount of a solute removed during a specified time period (hour, day, or week). A dialysis platform that has a high solute clearance rate but is performed intermittently (hemodialysis) may remove less solute over a week (ie, have a lower total solute removal) compared with a platform (peritoneal dialysis) that has a lower solute clearance rate but is continuous in nature. Total solute removal may differ depending upon the solute being evaluated (eg, urea versus beta2-microglobulin) and the dialysis modality being used (hemodialysis versus peritoneal dialysis).  

Solute transport rate — The solute transport rate is the rate at which solute moves from the blood compartment to the dialysate compartment during peritoneal dialysis (and conversely from dialysate to blood). The solute transport rate varies from patient to patient and may change over time in individual patients.

The solute transport rate is determined by a peritoneal equilibration test (PET). (See 'Peritoneal equilibration test' below and "Peritoneal equilibration test".)

Ultrafiltration — Ultrafiltration refers to the transport of water from blood to dialysate. The driving force for ultrafiltration is the glucose (or other osmotic or oncotic agent) present in dialysate. The ultrafiltration coefficient reflects the amount of ultrafiltration volume removed per gram of glucose absorbed. (See "Mechanisms of solute clearance and ultrafiltration in peritoneal dialysis".)

Peritoneal equilibration test — The PET is a highly reproducible procedure that characterizes solute transport and ultrafiltration across the peritoneal membrane. (See "Peritoneal equilibration test".)

The PET is performed in all patients in the months following initiation of peritoneal dialysis to classify membrane function so that the dialysis prescription can be optimized to specific membrane characteristics. This initial test provides a baseline for comparison if the rates of solute transport and ultrafiltration change over time. The PET is used as a diagnostic test to identify reasons for reduced solute clearance.

Based upon the results of the PET, patients are classified into one of the following transport categories. Each classification is discussed in depth elsewhere. (See "Peritoneal equilibration test", section on 'Peritoneal membrane function classification'.)

●High transporter (or fast transporter) – High transporters achieve the most rapid equilibration between blood and dialysate and thus, more rapidly lose the osmotic gradient required for ultrafiltration. High transporters remove solute well and tend to have adequate Kt/Vurea and creatinine clearance but may have difficulty removing fluid [6].

●Low transporter (or slow transporter) – Low transporters are characterized by slower and less complete equilibration. Low transporters maintain their intraperitoneal osmotic gradient and thereby ultrafilter fluid easily, but may have difficulty removing solute (ie, Kt/Vurea or creatinine clearance may be low) [6].

●Average transporter – Average transporters have values that are intermediate between high and low transporters.

ROUTINE MONITORING FOR ADEQUATE CLEARANCE — We routinely monitor all peritoneal dialysis patients to make sure the dialysis procedure is working adequately. The optimal frequency of monitoring is not known. We do the following:

●We assess volume status, monitor for uremic symptoms, and perform laboratory evaluation monthly. Laboratory evaluation for dialysis adequacy includes measurement of blood urea nitrogen (BUN), creatinine, and electrolytes. (As part of routine care of the dialysis patient, we also routinely follow calcium, phosphate, parathyroid hormone, complete blood count, iron, total iron-binding capacity, and ferritin, but these measurements are not directly used to monitor for dialysis adequacy.)

●We measure residual kidney function every other month. From a 24-hour urine collection, we calculate urea clearance using the urine volume, urine urea concentration, and plasma urea concentration. The calculation of residual kidney function and a representative example are provided elsewhere. (See 'Solute clearance' above.)

●We measure the total solute clearance (peritoneal dialysis Kt/Vurea + residual kidney function) every three to four months and anytime there is a progressive rise in the BUN. The patient submits a 24-hour urine collection and a 24-hour collection of total dialysis effluent (ie, total drain volume over 24 hours). We measure the total dialysate volume, dialysate urea concentration, and plasma urea concentration. The daily peritoneal urea clearance (Kt) is the product of the total 24-hour peritoneal drain volume and the ratio of the urea concentration in the pooled drained dialysate to that in the plasma (D/P urea). The calculation of Kt/Vurea and a representative example are provided elsewhere. (See "Prescribing peritoneal dialysis", section on 'Follow-up visits'.)

The goal Kt/Vurea in patients receiving peritoneal dialysis is discussed elsewhere. (See "Prescribing peritoneal dialysis", section on 'Optimal amount of dialysis (target Kt/Vurea)'.)

●We perform a peritoneal equilibration test (PET) if the peritoneal Kt/Vurea (ie, peritoneal clearance) is decreased from baseline while the residual kidney function remains stable. This is typically manifested by a decline in the drain volume without a change in the dwell time or the glucose solution. It is unusual for the Kt/Vurea to change from baseline without an intervening event, such as peritonitis. (See 'Measure solute clearance' below.)

●We review the prescription with the patient to ensure adherence with the peritoneal dialysis prescription. We review the volume of drains to ensure that drains are complete and the catheter is working properly.

EVALUATION — The major clinical findings associated with inadequate dialysis are volume overload, a progressively increasing blood urea nitrogen (BUN) and/or plasma creatinine concentration, and, occasionally, uremic symptoms.

Because we follow laboratory values closely, a progressive increase in the BUN or plasma creatinine is usually detected before the onset of uremic symptoms. However, changes in BUN do not always reflect inadequate dialysis and must be evaluated further. (See 'Causes of increased BUN' below.)

Occasionally, patients who are not closely monitored with laboratory tests may present with uremic symptoms. Such patients may require hemodialysis while the evaluation of peritoneal dialysis is ongoing. (See "Overview of the management of chronic kidney disease in adults", section on 'Indications for kidney replacement therapy'.)

Causes of increased BUN — Progressive increases in blood urea nitrogen (BUN) suggest that either more solute (and thus urea) is being produced or there is less clearance by dialysis and residual kidney function.

Increased production — The causes of increased solute production include the following:

●Dietary nonadherence – We generally recommend to patients a diet containing 1.2 to 1.3 g/kg/day of high-biological-value protein. When patients markedly increase dietary protein intake above this amount, the BUN often increases despite good clearances.

●Hypercatabolism – A hypercatabolic state can raise the BUN despite good clearances. Hypercatabolic states include acute illness (such as infection), increased tissue breakdown, metabolic acidosis, hyperthyroidism, or glucocorticoid use.

●Gastrointestinal bleeding – Severe gastrointestinal bleeding can increase the BUN. Severe bleeding is usually obvious based on history. Occult bleeding is not sufficient to cause an increased BUN. (See 'Approach to patients with increasing BUN or plasma creatinine concentration' below.)

Decreased clearance — Decreased solute clearance is due to the following:

●Nonadherence with the dialysis – Nonadherence with the dialysis regimen is a common cause of reduced solute clearance.

●Loss of residual kidney function – If residual kidney clearance is contributing to total solute clearance, a significant decrease in kidney function will decrease total solute clearance. This is reflected by a decrease in the 24-hour urea and creatinine clearances.

●Low peritoneal dialysis solute clearance – Occasionally, peritoneal dialysis is performed correctly by the patient (ie, according to the prescription) but the solute transport rate has changed since dialysis was first started. Changes in the solute transport rate are reflected in the peritoneal equilibration test (PET). The PET is most useful if a baseline test is available for comparison. (See 'Peritoneal equilibration test' above and "Peritoneal equilibration test", section on 'Diagnosis of causes of inadequate ultrafiltration and solute clearance'.)

Both a decrease and increase in the solute transport rate can reduce clearance.

If the solute transport rate has declined from baseline, the peritoneal dialysis solute clearance decreases. The solute transport rate is determined by the membrane surface area and the intrinsic transport capacity of the membrane. Decreased solute transport rate is almost always due to a loss of contact surface area rather than a change in the intrinsic transport capacity, although occasionally both are present, as in late stages of encapsulating peritoneal sclerosis (EPS). (See "Encapsulating peritoneal sclerosis in patients on peritoneal dialysis".)

Adhesions are a common cause of decreased surface area [7]. Adhesions are caused by blood, inflammation, and infection, often related to repeated episodes of severe peritonitis or abdominal surgery, particularly in the setting of bowel pathology.

Occasionally, an increase in the solute transport rate from a previously established baseline causes decreased solute removal. This appears counterintuitive since one expects more solute movement from blood to dialysate as diffusion rates increase. However, peritoneal dialysis solute clearance is determined by the final drain volume (instilled volume plus net ultrafiltration volume) and the concentration of the solute in the final drain volume. The drain volume is determined by the solute transport rate: If the solute transport rate is high, the osmotic gradient, which favors ultrafiltration, rapidly dissipates due to glucose absorption from dialysate into blood. As a result, if the dwell time is too long, much or all of the ultrafiltrated fluid, and, at times, even some of the initial instilled volume, may be reabsorbed/absorbed from the peritoneal cavity into postcapillary venules and lymphatics, resulting in low drain volumes and correspondingly low total solute clearance.

The rate of transport may transiently increase during an episode of peritonitis due to inflammation-related increases in perfusion of existing capillaries, which increases the capillary surface area. In such cases, the transport rate usually returns to baseline once peritonitis resolves.

In some patients, transport status slowly increases over time. This is thought to be due to angiogenesis resulting in an increase in the number of capillaries per unit space (capillary density), which also increases capillary surface area.

Approach to patients with increasing BUN or plasma creatinine concentration — The evaluation of peritoneal dialysis patients with increasing blood urea nitrogen (BUN) involves the assessment of production and clearance of solute and the assessment of adherence (algorithm 1).

Exclude increased production — We interview patients to assess adherence with diet. Protein intake above the recommended amount (ie, 1.2 to 1.3 g/kg/day of high-biological-value protein) will increase total solute and BUN production. We review dietary restrictions in order to increase adherence.

We review medications to see if the patient has been started on glucocorticoids as glucocorticoids will increased BUN production. We exclude other causes of hypercatabolism, including infection, tissue breakdown, metabolic acidosis, and hyperthyroidism. (See "Overview of the clinical manifestations of hyperthyroidism in adults" and "Diagnosis of hyperthyroidism" and "Non-access-related infections in patients on chronic dialysis".)

Treatment of the underlying cause for hypercatabolism will generally lower the BUN to the expected values.

We inquire as to a history of gastrointestinal bleeding. Severe gastrointestinal bleeding can increase the BUN independent of an increase in total solute production. Generally, the bleeding is obvious and not occult. (See "Evaluation of suspected small bowel bleeding (formerly obscure gastrointestinal bleeding)", section on 'Hemodynamically stable patients' and "Evaluation of occult gastrointestinal bleeding", section on 'Evaluation of a positive fecal occult blood test'.)

Assess adherence with peritoneal dialysis regimen — We ask patients whether they are compliant with the peritoneal dialysis prescription. We also estimate adherence with the prescription by assessing the patient's inventory of dialysis supplies. This is done by the nurse during home visits or by the person who delivers the patient's dialysis supplies.

Patients are frequently noncompliant with the prescribed peritoneal dialysis regimen, although it is difficult to document the incidence of nonadherence [8-12]. As many as 11 percent of patients who switch to hemodialysis do so because of nonadherence with peritoneal dialysis [3].

In continuous ambulatory peritoneal dialysis (CAPD) it is difficult to accurately measure adherence as it may not be reflected in the Kt/Vurea. Among patients who are nonadherent with dialysis, the calculated Kt/Vurea may be adequate because the patient has done the dialysis prescription exactly as prescribed on the day that they submit the 24-hour dialysate collection for testing but does not do the entire prescription on other days. In this case, the calculated weekly total solute clearance (Kt/Vurea) is an overestimate of amount of dialysis typically being performed.

Among patients on automated peritoneal dialysis (APD)/continuous cycler peritoneal dialysis (CCPD), software may be available within the cycler that records the patient's daily dwells and drains so the number of actual treatments performed is available.

Measure solute clearance — Among patients with progressively increasing BUN or plasma creatinine concentration, we measure the total solute clearance (peritoneal dialysis Kt/Vurea + 24-hour urea clearance) as described above. (See 'Routine monitoring for adequate clearance' above.)

Patients who appear to be adherent with peritoneal dialysis and have reduced total solute clearance from their usual baseline require further evaluation and often a change in the peritoneal dialysis prescription in order to increase clearance. Our approach depends on whether the Kt/Vurea or 24-hour urea clearance has declined.

Reduced residual kidney function — It is common for residual kidney function to decline at some point after starting dialysis. This is reflected by a decrease in the 24-hour urea clearance. Among such patients, although the total solute clearance is decreased, the Kt/Vurea is unchanged.

For such patients, we increase the dialysis dose, usually by increasing the volume of exchanges or the number of exchanges.

Reduced peritoneal dialysis solute clearance (Kt/Vurea) — Occasionally, the residual kidney function is unchanged, but the peritoneal dialysis solute clearance has declined, as reflected in the Kt/V. We perform a PET in such patients to re-evaluate solute transport characteristics of the peritoneal membrane. We adjust the dialysis prescription based on the results of the PET [7]. (See "Evaluating patients for chronic peritoneal dialysis and selection of modality", section on 'Initial modality'.)

Low transporters — We initially try to provide more dialysis by increasing the volume of inflow dialysate per exchange. We do not increase the number of exchanges, since this decreases the actual time of contact between dialysate and peritoneal membrane and may decrease the dialysate to plasma ratio (D/P urea), which determines the Kt/Vurea. An exception is patients on APD who do all exchanges at night (called nocturnal intermittent PD [NIPD]). Among such patients, if increasing the instilled volume per exchange is intolerable or ineffective, then adding a daytime dwell may be helpful. If the patient is on NIPD with a daytime dwell, then adding a midday exchange may help achieve target clearance.

If these measures do not sufficiently improve solute clearances, then transfer of the patient to hemodialysis may be necessary. Occasionally, we combine hemodialysis and peritoneal dialysis in order to achieve clearance targets, but this is uncommon. In our experience, adequate solute clearance can usually be achieved if the center is willing to individualize the patient's prescription and the patient is willing to do what is needed to reach target (such as doing a midday exchange if on APD). An exception is very large patients who have no residual kidney function who may not easily reach peritoneal dialysis Kt/Vurea targets.

There are no pharmacologic therapies that improve peritoneal transport and solute clearances. If the change in transport is due to loss of surface area contact due to multiple adhesions, laparoscopic lysis of adhesions by surgeons who are trained in this technique may restore contact surface area, although this is rarely done in practice.

High transporters — If the solute transport rate has increased, we increase the instilled volume per exchange and decrease the dwell time. Increasing the instilled volume slows the rate at which equilibrium is reached and increases the drain volume, which increases net solute clearance. Shortening the dwell time decreases the amount of time available for fluid absorption by lymphatics and postcapillary venules. Shortening the dwell time generally entails adding more exchanges per day (often achieved by adding a midday exchange).

SUMMARY AND RECOMMENDATIONS

●The goals of peritoneal dialysis are to remove solute and fluid. If the dialysis procedure does not remove sufficient solute or fluid, uremia and volume overload may result. (See 'Introduction' above.)

●Peritoneal dialysis patients are closely monitored for volume status and appearance of uremic symptoms. We perform regularly scheduled laboratory evaluation and routinely measure total solute clearance, which is the sum of residual kidney function (determined by 24-hour urea clearance) and peritoneal dialysis solute clearance (determined by the Kt/Vurea). Our approach and frequency of monitoring are defined. (See 'Routine monitoring for adequate clearance' above.)

●Blood urea nitrogen (BUN) and plasma creatinine concentration are markers for solute clearance. Increasing BUN may be due to increased production or decreased clearance of solute or to gastrointestinal bleeding. Our approach to the evaluation of progressively increasing BUN is defined above. (See 'Causes of increased BUN' above and 'Approach to patients with increasing BUN or plasma creatinine concentration' above.)

●If the patient is adherent with the peritoneal dialysis prescription, then decreased solute clearance may be due to a decrease in residual kidney function or low peritoneal dialysis solute clearance. These are distinguished by analysis of individual components of the measured total solute clearance (ie, either peritoneal dialysis Kt/Vurea or 24-hour urea clearance). The peritoneal dialysis dose must be increased if residual kidney function decreases. (See 'Measure solute clearance' above.)

●If peritoneal dialysis solute clearance is decreased, we perform a peritoneal equilibration test (PET) to characterize the solute transport rate. The peritoneal dialysis prescription is adjusted based on whether patients are low or high solute transporters. (See 'Reduced peritoneal dialysis solute clearance (Kt/Vurea)' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges William L Henrich, MD, MACP, who contributed to earlier versions of this topic review.