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).

Adequate solute removal by dialysis controls uremic symptoms and optimizes mineral metabolism and electrolyte values. To achieve adequate solute removal, some clinicians target a minimum amount of measured small-solute clearance (from dialysis and residual kidney function) and some do not [1]. (See "Prescribing peritoneal dialysis", section on 'Targeted versus untargeted dialysis'.)

This topic reviews the evaluation and management of patients on peritoneal dialysis who have inadequate solute removal, whether based on measurement of total small-solute clearance or on clinical assessment. The discussion assumes that solute removal was initially adequate and has become impaired over time.

A review of the factors that must be considered at the initiation of peritoneal dialysis, the management of patients with ultrafiltration failure and volume overload, and the factors that regulate solute and water transport across the peritoneal membrane are presented separately:

●(See "Evaluating patients for chronic peritoneal dialysis and selection of modality".)

●(See "Management of hypervolemia in patients on peritoneal dialysis".)

●(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 (eg, mL/min, L/day, or L/week). Total solute clearance refers to the clearance provided by both dialysis and the remaining native kidney function (termed residual kidney function). The blood urea nitrogen (BUN) and serum creatinine are commonly used as markers for total small solute clearance in peritoneal dialysis patients. A progressive increase in the serum concentration of either marker suggests that small solute clearance has decreased, or production of the marker has increased. (See 'Causes of increased BUN' below.)

Two metrics are commonly used to assess small solute clearance by peritoneal dialysis: weekly Kt/Vurea and 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 KDOQI emphasis on Kt/Vurea was based on simplification: Kt/Vurea was used to assess hemodialysis dose and equivalence between dialysis modalities was sought. However, creatinine clearance is typically less variable than Kt/Vurea, which can be affected by a number of factors, and some clinicians continue to use both metrics. (See "Measurement of solute clearance in continuous peritoneal dialysis: Kt/V and creatinine clearance".)

Calculation of the total weekly Kt/Vurea requires measuring BUN and the urea concentrations in and volumes of a 24-hour collection of drained peritoneal fluid and a 24-hour urine sample. This is described in detail elsewhere. (See "Prescribing peritoneal dialysis", section on 'Kt/Vurea'.)

Solute transfer (transport) rate — The solute transfer 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). Solute transfer is commonly referred to as solute “transport” by many clinicians; however, some experts discourage the use of the term “transport” since it wrongly suggests that the movement of solutes across the peritoneal membrane occurs by an active process rather than by passive diffusion [6].

The solute transfer rate varies from patient to patient, may change over time in individual patients, and is quantitatively assessed by the peritoneal equilibration test (PET). A baseline PET is performed on every patient shortly after initiating peritoneal dialysis. (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 the solute transfer (transport) rate 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 the specific membrane characteristics. This initial test provides a baseline for comparison if the rates of solute transfer 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, the peritoneal membrane is classified into one of the following solute transfer categories. Each classification is discussed in depth elsewhere. (See "Peritoneal equilibration test", section on 'Peritoneal membrane function classification'.)

●Fast solute transfer – Patients with fast, or high, solute transfer (transport) achieve the most rapid equilibration between blood and dialysate and thus, more rapidly lose the osmotic gradient required for ultrafiltration. Such patients remove solute well and tend to have adequate Kt/Vurea and creatinine clearance but may have difficulty removing fluid [7].

●Slow solute transfer – Patients with slow, or low, solute transfer (transport) are characterized by slower and less complete equilibration. Such patients 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) [7].

●Average solute transfer – Patients with average solute transfer (transport) rates have values that are between those of patients with fast and slow solute transfer.

CAUSES OF INCREASED BUN — 

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

Increased production — The causes of increased BUN 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.

Decreased clearance — Decreased urea clearance is due to one or more of the following:

Nonadherence with dialysis — Nonadherence with the dialysis regimen is a common cause of reduced solute clearance. (See 'Assess adherence with dialysis' below.)

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 urine urea and creatinine clearances.

Low peritoneal solute clearance — Occasionally, peritoneal dialysis is performed correctly by the patient (ie, according to the prescription) but solute clearance has decreased due to changes in the solute transfer (transport) rate since dialysis was first started. Changes in the solute transfer 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 decreases and increases in the peritoneal membrane solute transfer rate can reduce clearance, albeit by different mechanisms:

●A decrease in the solute transfer rate from baseline causes decreased solute removal. The solute transfer rate is determined by the membrane surface area and the intrinsic transport capacity of the membrane. Decreased solute transfer 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 [8]. 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.

●An increase in the solute transfer rate from baseline also may cause decreased solute removal. This appears counterintuitive since one expects more solute movement from blood to dialysate as diffusion rates increase. However, peritoneal dialysis solute removal 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 transfer rate: If the solute transfer 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 ultrafiltrate, 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 removal.

The solute transfer rate 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 transfer rate usually returns to baseline once peritonitis resolves.

In some patients, the solute transfer rate 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. (See "Rapid transport (fast solute transfer) in peritoneal dialysis".)

ROUTINE MONITORING FOR ADEQUATE CLEARANCE — 

We routinely monitor 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 dialysis care, we also 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 assess patient-reported daily urine output monthly. We measure residual kidney function monthly, though some clinicians do so less frequently (eg, every other month or quarterly). 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 and "Prescribing peritoneal dialysis", section on 'Kt/Vurea'.)

●We assess the total (ie, peritoneal plus residual kidney) solute clearance by calculating peritoneal dialysis Kt/Vurea and urine Kt/Vurea every three to four months and anytime there is a progressive rise in the BUN (see "Prescribing peritoneal dialysis", section on 'Follow-up visits'). The calculation of Kt/Vurea and a representative example are provided elsewhere. (See "Prescribing peritoneal dialysis", section on 'Kt/Vurea'.)

The goal Kt/Vurea in patients receiving peritoneal dialysis is discussed elsewhere. (See "Prescribing peritoneal dialysis", section on 'Targeted versus untargeted dialysis'.)

●If the peritoneal Kt/Vurea has decreased despite an unchanged peritoneal dialysis prescription, we perform a peritoneal equilibration test (PET) to compare with the baseline PET (see 'Peritoneal equilibration test' above). Changes in peritoneal membrane characteristics, if they occur, are typically gradual; it is unusual for the peritoneal Kt/Vurea to change suddenly without an intervening event (eg, peritonitis). (See 'Assess 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 uremic symptoms. 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' above and 'Exclude increased BUN production' below.)

Exclude increased BUN production — The evaluation of peritoneal dialysis patients with increasing BUN involves the assessment of production and removal of solute and the assessment of adherence (algorithm 1). Our approach to evaluating potential causes of increased BUN production is as follows:

●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 to increase adherence.

●We review medications to see if the patient has been started on glucocorticoids as glucocorticoids will increase 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 dialysis — Patients are frequently nonadherent with the prescribed peritoneal dialysis regimen [3], and it can be difficult to document nonadherence [9-13]. Among patients who are nonadherent with dialysis, the peritoneal Kt/Vurea may be adequate only because the patient has done the dialysis prescription exactly as prescribed on the day that they submit the 24-hour dialysate collection for testing. If the patient does not do the entire prescription on other days, the calculated weekly Kt/Vurea is an overestimate of the amount of dialysis being performed.

We ask all patients whether they adhere to the peritoneal dialysis prescription. Additional approaches to assessing adherence depend on the dialysis modality:

●For patients on automated peritoneal dialysis (APD), modern cyclers transmit treatment data to clinicians, allowing for remote monitoring of treatment adherence [14].

●For patients on continuous ambulatory peritoneal dialysis (CAPD), remote monitoring is unavailable. We estimate adherence with the CAPD 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. Increases in serum creatinine concentration also may be helpful in assessing suboptimal adherence to CAPD.

Assess solute clearance — Among patients who have progressively increasing BUN or plasma creatinine concentration despite adherence to the peritoneal dialysis regimen, we assess total (ie, peritoneal plus residual kidney) solute removal by calculating the peritoneal and urine Kt/Vurea (see 'Solute clearance' above and "Prescribing peritoneal dialysis", section on 'Kt/Vurea'). The most common reason for a decline in total Kt/Vurea is a loss in residual kidney function.

Patients who have reduced total solute removal from their usual baseline generally require a change in the peritoneal dialysis prescription. Our approach depends on whether the peritoneal or residual kidney urea clearance has declined. (See 'Management' below.)

MANAGEMENT — 

The management of patients with decreased solute removal depends on the cause.

Patients with reduced residual kidney function — For patients with reduced urine Kt/Vurea, we increase the dialysis dose. This is usually done by increasing the fill volumes or the number of exchanges. An illustrative example of formulating a new dialysis prescription is provided elsewhere. (See "Prescribing peritoneal dialysis", section on 'Adjustment in prescription'.)

Patients with reduced peritoneal Kt/Vurea — Less commonly, the residual kidney function is unchanged but the peritoneal dialysis solute removal has declined, as reflected in the peritoneal Kt/V. In such patients, we perform a peritoneal equilibration test (PET) to re-evaluate solute transfer (transport) characteristics of the peritoneal membrane (see 'Peritoneal equilibration test' above); both decreases and increases in the peritoneal membrane solute transfer rate can reduce clearance. (See 'Low peritoneal solute clearance' above.)

We adjust the dialysis prescription based on the results of the PET [8] as follows:

Slow solute transfer (transport) — For patients in whom the solute transfer rate has decreased (ie, “slow transporters” or “low transporters”), we initially try to provide more dialysis by increasing the volume of inflow dialysate per exchange. We typically 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 peritoneal Kt/Vurea. An exception is patients on automated peritoneal dialysis (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 a patient on APD already has a daytime dwell, then adding a midday exchange may help achieve target solute removal. Another alternative for patients on APD is to add time on the cycler. For example, if the total cycler duration was 8 hours, increasing that to 9 or 10 hours, with or without another exchange, can increase solute removal.

If these measures do not sufficiently improve solute removal, then transfer of the patient to hemodialysis may be necessary. In our experience, adequate solute removal 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 membrane solute transfer. If the reduction in solute transfer 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.

Fast solute transfer (transport) — For patients in whom the solute transfer rate has increased (ie, “fast transporters” or “high transporters”), 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 removal. 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

●Solute clearance in peritoneal dialysis – The goals of peritoneal dialysis are to remove solute and fluid. Adequate solute removal by dialysis controls uremic symptoms and optimizes mineral metabolism and electrolyte values. (See 'Introduction' above and 'Definitions of terms' above.)

●Increased blood urea nitrogen – Blood urea nitrogen (BUN) and plasma creatinine concentration are markers for solute clearance. However, increases in BUN do not always reflect inadequate dialysis. Increasing BUN may be due to increased production, gastrointestinal bleeding, or decreased clearance of solute. (See 'Causes of increased BUN' above and 'Exclude increased BUN production' above.)

●Monitoring – Patients on peritoneal dialysis are closely monitored for volume status and appearance of uremic symptoms. We perform regularly scheduled laboratory evaluation and routinely assess total (ie, peritoneal plus residual kidney) solute removal by calculating peritoneal and urine Kt/Vurea. (See 'Routine monitoring for adequate clearance' above.)

●Evaluation – If the patient is adherent with the peritoneal dialysis prescription, then inadequate solute removal may be due to a decrease in residual kidney function or, less commonly, to a decrease in peritoneal dialysis solute removal. These are distinguished by analysis of individual components of the total Kt/Vurea (ie, peritoneal Kt/Vurea + urine Kt/Vurea). (See 'Assess adherence with dialysis' above and 'Assess solute clearance' above.)

●Management – The management of patients with decreased solute removal depends on the cause. For patients with reduced residual kidney function, the dialysis dose is increased. If peritoneal dialysis solute removal has decreased, a peritoneal equilibration test (PET) is performed to evaluate solute transfer (transport) characteristics of the peritoneal membrane. The dialysis prescription is adjusted based on the results of the PET. (See 'Management' above.)

ACKNOWLEDGMENT — 

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