Relationships between Peritoneal Protein Clearance and Parameters of Fluid Status Agree with Clinical Observations in other Diseases that Venous Congestion Increases Microvascular Protein Escape

Krediet, Raymond T.; Yoowannakul, Suree; Harris, Lauren S.; Davenport, Andrew

doi:10.3747/pdi.2018.00016

Cited by 17 publications

(18 citation statements)

References 43 publications

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“…This association was found in both univariable and multivariable analyses. The results are in close agreement with those of a previously published study in incident PD patients from the UK [19]. The presence of venous congestion, assessed by an in- creased right atrial diameter and elevated serum NT-proBNP, was independently associated with PPCl in that analysis.…”

Section: Discussionsupporting

confidence: 91%

“…It has been shown recently that both serum NT-proBNP and right atrial area are independently and positively associated with PPCl. These findings mean that venous congestion is likely to be important in PPL [19]. Fluid volume overload can lead to venous congestion and is a recognized independent predictor of cardiovascular events and mortality in PD patients [20][21][22].…”

Section: Introductionmentioning

confidence: 99%

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Overhydration May Be the Missing Link between Peritoneal Protein Clearance and Mortality

Guedes

Marques

Domingos

et al. 2021

Nephron

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Introduction: Peritoneal protein loss (PPL) has been associated with mortality. Inflammation was assumed a putative cause with malnutrition as a consequence. Hydrostatic convection is a major drive for microvascular protein transport, but most studies in peritoneal dialysis (PD) patients overlooked this mechanism. An association between peritoneal protein clearance (PPCl) and venous congestion has been reported recently. The aim of this study was to explore the importance of fluid overload in PPCl in PD. Methods: Sixty-seven prevalent PD patients were assessed with peritoneal equilibration test and multifrequency bioelectrical impedance assessment (BIA). PPL and PPCl were calculated from simultaneously obtained 24-h peritoneal effluent. Results: PPL averaged 5.2 g/24 h. It was higher in patients on continuous treatment than in those without a long dwell. Significant associations between PPCl and BIA parameters of overhydration were found in both univariable and multivariable analyses. Lean mass index, partly dependent on hydration status, was associated with PPCl in univariable but not in multivariable analysis. A multiple linear model identified extracellular water excess and higher D/P creatinine as predictors of higher PPCl, independent of PD duration, type of PD, age, gender, albumin, cardiovascular disease, C-reactive protein, or lean mass index. Conclusions: The uni- and multivariable strong associations between fluid overload and PPCl support the importance of hydrostatic pressure-induced convection for PPCl. Also, peritoneal small solute transport was associated with PPCl. Both are amenable by adjusted dialysis prescription, especially focused on fluid status and avoidance of overhydration. The assumption of an association with inflammation and malnutrition was not confirmed.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Overhydration May Be the Missing Link between Peritoneal Protein Clearance and Mortality

Guedes

Marques

Domingos

et al. 2021

Nephron

Self Cite

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“…125 Hydrostatic back-pressure in patients with right-sided heart failure has also been proposed as a possible mechanism. 128 It is important to say something about how peritoneal protein loss is measured and whether it is expressed as total loss or clearance as these are reported differently. Protein loss is the direct measurement of dialysate protein, typically over 24 h (expressed in mg or g/d), whereas the clearance would be this value divided by the serum total protein (expressed as per unit time, such as mL/min, or L/week).…”

Section: Interpreting Sodium Sieving/dip (Underpins Guideline 4b)mentioning

confidence: 99%

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

et al. 2021

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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)

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“…It is unlikely that the volume changes observed in this study were due to the ultrafiltration of extracellular fluid from the peritoneum into the peritoneal cavity, first because BIA cannot distinguish between extracellular fluid in interstitial, intravascular, or intra-abdominal spaces and therefore cannot be sensitive to local ultrafiltration, and then because BIA in W2A configuration is insensitive to changes in trunk volume. The absence of an expected correlation of resistance or volume changes with Vu 35 is in support of these explanations.…”

Section: Discussionmentioning

confidence: 69%

Supine equilibration of extracellular fluid in peritoneal dialysis varies with intra-abdominal pressure

et al. 2020

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Background: Increased intra-abdominal pressure (PIA) leads to venous congestion in splanchnic and adjoining circulations. The aim is to examine whether PIA in peritoneal dialysis (PD) affects the mobilization of extracellular fluid from the lower body in supine body position. Methods: Patients were studied during a regular peritoneal equilibration test (PET) in supine body position using multifrequency bioimpedance analysis to determine extracellular resistance and absolute volume overload (AVO) in wrist-to-ankle (W2A) as well as in ankle-to-ankle (A2A) configurations. Measurements were taken at baseline (T0) after draining the peritoneal cavity, at T1 shortly after filling with 2 L of standard dialysate, and at T2 before taking the 2 h PET samples. PIA was measured from the column height in the PD catheter. Extracellular resistance in the lower extremities (RL) was taken as half of the A2A resistance. Results: Eighteen patients (56 ± 15 years, 76 ± 21 kg, body mass index (BMI) 26.4 ± 7 kg/m2, 13 men) were studied. After having assumed a supine body position for the duration of 17, 77, and 155 min, AVO continuously decreased from 1.6 ± 1.3 (T0) to 1.2 ± 1.5 (T1) and 1.0 ± 1.4 L (T2). RL significantly increased from 238 ± 57 (T0) to 254 ± 62 (T1) and 264 ± 67 Ohm (T2). This increase was negatively correlated to BMI and PIA measured at any time point, but not to net ultrafiltration volume. Conclusions: Orthostatic fluid shifts from the lower limbs may take up to 2 h in supine PD patients, especially with high BMI and PIA because of venous congestion in splanchnic and adjoining circulations.

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Relationships between Peritoneal Protein Clearance and Parameters of Fluid Status Agree with Clinical Observations in other Diseases that Venous Congestion Increases Microvascular Protein Escape

Cited by 17 publications

References 43 publications

Overhydration May Be the Missing Link between Peritoneal Protein Clearance and Mortality

Overhydration May Be the Missing Link between Peritoneal Protein Clearance and Mortality

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

Supine equilibration of extracellular fluid in peritoneal dialysis varies with intra-abdominal pressure

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