ISPD recommendations for the evaluation of peritoneal membrane dysfunction in adults: Classification, measurement, interpretation and rationale for intervention

Abstract

Peritoneal dialysis (PD) uses the peritoneal membrane for dialysis. The peritoneal membrane is a thin layer of tissue that lines the abdomen. The lining is used as a filter to help remove extra fluid and poisonous waste from the blood. Everybody is unique. What is normal for one person’s membrane may be very different from another person’s. The kidney care team wants to provide each person with the best dialysis prescription for them and to do this they must evaluate the person’s peritoneal lining. Sometimes dialysis treatment itself can cause the membrane to change after some years. This means more assessments (evaluations) will be needed to determine whether the person’s peritoneal membrane has changed. Changes in the membrane may require changes to the dialysis prescription. This is needed to achieve the best dialysis outcomes. A key tool for these assessments is the peritoneal equilibration test (PET). It is a simple, standardized and reproducible tool. This tool is used to measure the peritoneal function soon after the start of dialysis. The goal is to understand how well the peritoneal membrane works at the start of dialysis. Later on in treatment, the PET helps to monitor changes in peritoneal function. If there are changes between assessments causing problems, the PET data may explain the cause of the dysfunction. This may be used to change the dialysis prescription to achieve the best outcomes. The most common problem with the peritoneal membrane occurs when fluid is not removed as well as it should be. This happens when toxins (poisons) in the blood cross the membrane more quickly than they should. This is referred to as a fast peritoneal solute transfer rate (PSTR). Since more efficient fluid removal is associated with better outcomes, developing a personal PD prescription based on the person’s PSTR is critically important. A less common problem happens when the membrane fails to work properly (also called membrane dysfunction) because the peritoneal membrane is less efficient, either at the start of treatment or developing after some years. If membrane dysfunction gets worse over time, then this is associated with progressive damage, scarring and thickening of the membrane. This problem can be identified through another change of the PET. It is called reduced ‘sodium dip’. Membrane dysfunction of this type is more difficult to treat and has many implications for the individual. If the damage is major, the person may need to stop PD. They would need to begin haemodialysis treatment (also spelled hemodialysis). This is a very important and emotional decision for individuals with kidney failure. Any decision that involves stopping PD therapy or transitioning to haemodialysis therapy should be made jointly between the clinical team, the person on dialysis and a caregiver, if requested. Although evidence is lacking about how often tests should be performed to determine peritoneal function, it seems reasonable to repeat them whenever there is difficulty in removing the amount of fluid necessary for maintaining the health and well-being of the individual. Whether routine evaluation of membrane function is associated with better outcomes has not been studied. Further research is needed to answer this important question as national policies in many parts of the world and the COVID-19 has placed a greater emphasis and new incentives encouraging the greater adoption of home dialysis therapies, especially PD. For Chinese and Spanish Translation of the Lay Summary, see Online Supplement Appendix 1. Guideline 1: A pathophysiological taxonomy: A pathophysiological classification of membrane dysfunction, which provides mechanistic links to functional characteristics, should be used when prescribing individualized dialysis or when planning modality transfer (e.g. to automated peritoneal dialysis (PD) or haemodialysis) in the context of shared and informed decision-making with the person on PD, taking individual circumstances and treatment goals into account. (practice point) Guideline 2a: Identification of fast peritoneal solute transfer rate (PSTR): It is recommended that the PSTR is determined from a 4-h peritoneal equilibration test (PET), using either 2.5%/2.27% or 4.25%/3.86% dextrose/glucose concentration and creatinine as the index solute. (practice point) This should be done early in the course dialysis treatment (between 6 weeks and 12 weeks) (GRADE 1A) and subsequently when clinically indicated. (practice point) Guideline 2b: Clinical implications and mitigation of fast solute transfer: A faster PSTR is associated with lower survival on PD. (GRADE 1A) This risk is in part due to the lower ultrafiltration (UF) and increased net fluid reabsorption that occurs when the PSTR is above the average value. The resulting lower net UF can be avoided by shortening glucose-based exchanges, using a polyglucose solution (icodextrin), and/or prescribing higher glucose concentrations. (GRADE 1A) Compared to glucose, use of icodextrin can translate into improved fluid status and fewer episodes of fluid overload. (GRADE 1A) Use of automated PD and icodextrin may mitigate the mortality risk associated with fast PSTR. (practice point) Guideline 3: Recognizing low UF capacity: This is easy to measure and a valuable screening test. Insufficient UF should be suspected when either (a) the net UF from a 4-h PET is <400 ml (3.86% glucose/4.25% dextrose) or <100 ml (2.27% glucose /2.5% dextrose), (GRADE 1B) and/or (b) the daily UF is insufficient to maintain adequate fluid status. (practice point) Besides membrane dysfunction, low UF capacity can also result from mechanical problems, leaks or increased fluid absorption across the peritoneal membrane not explained by fast PSTR. Guideline 4a: Diagnosing intrinsic membrane dysfunction (manifesting as low osmotic conductance to glucose) as a cause of UF insufficiency: When insufficient UF is suspected, the 4-h PET should be supplemented by measurement of the sodium dip at 1 h using a 3.86% glucose/4.25% dextrose exchange for diagnostic purposes. A sodium dip ≤5 mmol/L and/or a sodium sieving ratio ≤0.03 at 1 h indicates UF insufficiency. (GRADE 2B) Guideline 4b: Clinical implications of intrinsic membrane dysfunction (de novo or acquired): in the absence of residual kidney function, this is likely to necessitate the use of hypertonic glucose exchanges and possible transfer to haemodialysis. Acquired membrane injury, especially in the context of prolonged time on treatment, should prompt discussions about the risk of encapsulating peritoneal sclerosis. (practice point) Guideline 5: Additional membrane function tests: measures of peritoneal protein loss, intraperitoneal pressure and more complex tests that estimate osmotic conductance and ‘lymphatic’ reabsorption are not recommended for routine clinical practice but remain valuable research methods. (practice point) Guideline 6: Socioeconomic considerations: When resource constraints prevent the use of routine tests, consideration of membrane function should still be part of the clinical management and may be inferred from the daily UF in response to the prescription. (practice point)

Survival of Peritoneal Membrane Function on Biocompatible Dialysis Solutions in a Peritoneal Dialysis Cohort Assessed by a Novel Test

“…Different tests have been developed, such as a modified PET with 3.86% glucose dialysate, a mini PET test and a PDC test that can give more information about FWT, osmotic conductance, sodium sieving and UF failure [7]. Recent ISPD guidelines encourage the use of these tests [8], but unfortunately, none of them can give all the relevant information concurrently. La Milia [9] and Cnossen [10] et al described a combination of modified and mini PET test in order to benefit from the advantages of both tests (called uni-PET or two-in-one modified PET).…”

Assessing Mechanical Catheter Dysfunction in Peritoneal Dialysis Patients: A Case Control, Proof-of-Concept Study

“…Recent ISPD guidelines recommend that mechanical problems should be excluded prior to membrane function testing in patients with insu cient UF capacity. However, there exists no standard protocol on how to diagnose catheter dysfunction [5].…”

“…The time-period selected for the analysis of the control group was seven days selected randomly depending on data availability, within a pre-de ned time window between 1 and 3 months after the start of PD. This time window was chosen considering the appearance of changes of peritoneal membrane function parameters early after PD start that may in uence ultra ltration [5].…”

“…Therefore, the recent ISPD guidelines recommend that low UF capacity should be evaluated by considering mechanical drainage problems rst, before suspecting membrane dysfunction [5]. Previous publications have suggested the association of slow drainage of PD uid, poor net UF or constant alarms during cycler treatment with catheter dysfunction [6,7].…”

Assessing transport across the peritoneal membrane: Precision medicine in dialysis

“…Other causes of membrane dysfunction include mechanical problems affecting the dialysate drainage, leaks of dialysate, high intraperitoneal pressure causing reverse fluid absorption or excessive lymphatic absorption: they can also be assessed by specific tests. 12…”