The impact of amino acid dialysate on anthropometric measures in adult patients on peritoneal dialysis: A systematic review and meta-analysis

Background: Glucose-containing dialysate underpins peritoneal dialysis (PD) therapy. However, its use is associated with amino acid loss in the dialysis effluent, a risk factor for protein-energy wasting (PEW) in PD patients. Amino acid-based dialysis solutions (AAD) may ameliorate this loss. However, the evidence of clinical benefit in preventing PEW is unclear. The aim of this review was to assess the effect of AAD versus standard dialysis solutions (STD) on anthropometric measures and serum albumin. Methods: Studies up until 30 September 2020 were identified from databases including MEDLINE and Embase, using a prespecified protocol (PROSPERO – CRD42020209581). Studies evaluating adults on PD were included. Data pertaining to muscle mass (primary outcome), other anthropometric measures and serum albumin were extracted. A meta-analysis of the eligible studies was conducted. Results: A total of 6945 abstracts were reviewed, from which 14 studies (9 randomised and 5 non-randomised) were included. There was no significant difference in any of the anthropometric measures, between AAD and STD during follow-up. Serum albumin at 6 months was statistically lower with AAD compared to STD [mean difference = −0.89 (95%CI −1.77 to −0.01, p = 0.046)]. The quality of evidence was graded low for each outcome. Conclusions: AAD may not alter anthropometric measures when compared to STD. The impact on serum albumin is uncertain, with an estimated difference that is unlikely to be of clinical value. These findings should be cautiously interpreted due to low quality of the evidence. Robust studies are needed to address the limitations in evidence.

How to Improve the Biocompatibility of Peritoneal Dialysis Solutions (without Jeopardizing the Patient’s Health)

Peritoneal dialysis (PD) is an important, if underprescribed, modality for the treatment of patients with end-stage kidney disease. Among the barriers to its wider use are the deleterious effects of currently commercially available glucose-based PD solutions on the morphological integrity and function of the peritoneal membrane due to fibrosis. This is primarily driven by hyperglycaemia due to its effects, through multiple cytokine and transcription factor signalling—and their metabolic sequelae—on the synthesis of collagen and other extracellular membrane components. In this review, we outline these interactions and explore how novel PD solution formulations are aimed at utilizing this knowledge to minimise the complications associated with fibrosis, while maintaining adequate rates of ultrafiltration across the peritoneal membrane and preservation of patient urinary volumes. We discuss the development of a new generation of reduced-glucose PD solutions that employ a variety of osmotically active constituents and highlight the biochemical rationale underlying optimization of oxidative metabolism within the peritoneal membrane. They are aimed at achieving optimal clinical outcomes and improving the whole-body metabolic profile of patients, particularly those who are glucose-intolerant, insulin-resistant, or diabetic, and for whom daily exposure to high doses of glucose is contraindicated.

ISPD guidelines for peritoneal dialysis in acute kidney injury: 2020 Update (paediatrics)

Peritoneal dialysis (PD) for acute kidney injury (AKI) in children has a long track record and shows similar outcomes when compared to extracorporeal therapies. It is still used extensively in low resource settings as well as in some high resource regions especially in Europe. In these regions, there is particular interest in the use of PD for AKI in post cardiac surgery neonates and low birthweight neonates. Here, we present the update of the International Society for Peritoneal Dialysis guidelines for PD in AKI in paediatrics. These guidelines extensively review the available literature and present updated recommendations regarding peritoneal access, dialysis solutions and prescription of dialysis. Summary of recommendations 1.1 Peritoneal dialysis is a suitable renal replacement therapy modality for treatment of acute kidney injury in children. (1C) 2. Access and fluid delivery for acute PD in children. 2.1 We recommend a Tenckhoff catheter inserted by a surgeon in the operating theatre as the optimal choice for PD access. (1B) (optimal) 2.2 Insertion of a PD catheter with an insertion kit and using Seldinger technique is an acceptable alternative. (1C) (optimal) 2.3 Interventional radiological placement of PD catheters combining ultrasound and fluoroscopy is an acceptable alternative. (1D) (optimal) 2.4 Rigid catheters placed using a stylet should only be used when soft Seldinger catheters are not available, with the duration of use limited to <3 days to minimize the risk of complications. (1C) (minimum standard) 2.5 Improvised PD catheters should only be used when no standard PD access is available. (practice point) (minimum standard) 2.6 We recommend the use of prophylactic antibiotics prior to PD catheter insertion. (1B) (optimal) 2.7 A closed delivery system with a Y connection should be used. (1A) (optimal) A system utilizing buretrols to measure fill and drainage volumes should be used when performing manual PD in small children. (practice point) (optimal) 2.8 In resource limited settings, an open system with spiking of bags may be used; however, this should be designed to limit the number of potential sites for contamination and ensure precise measurement of fill and drainage volumes. (practice point) (minimum standard) 2.9 Automated peritoneal dialysis is suitable for the management of paediatric AKI, except in neonates for whom fill volumes are too small for currently available machines. (1D) 3. Peritoneal dialysis solutions for acute PD in children 3.1 The composition of the acute peritoneal dialysis solution should include dextrose in a concentration designed to achieve the target ultrafiltration. (practice point) 3.2 Once potassium levels in the serum fall below 4 mmol/l, potassium should be added to dialysate using sterile technique. (practice point) (optimal) If no facilities exist to measure the serum potassium, consideration should be given for the empiric addition of potassium to the dialysis solution after 12 h of continuous PD to achieve a dialysate concentration of 3–4 mmol/l. (practice point) (minimum standard) 3.3 Serum concentrations of electrolytes should be measured 12 hourly for the first 24 h and daily once stable. (practice point) (optimal) In resource poor settings, sodium and potassium should be measured daily, if practical. (practice point) (minimum standard) 3.4 In the setting of hepatic dysfunction, hemodynamic instability and persistent/worsening metabolic acidosis, it is preferable to use bicarbonate containing solutions. (1D) (optimal) Where these solutions are not available, the use of lactate containing solutions is an alternative. (2D) (minimum standard) 3.5 Commercially prepared dialysis solutions should be used. (1C) (optimal) However, where resources do not permit this, locally prepared fluids may be used with careful observation of sterile preparation procedures and patient outcomes (e.g. rate of peritonitis). (1C) (minimum standard) 4. Prescription of acute PD in paediatric patients 4.1 The initial fill volume should be limited to 10–20 ml/kg to minimize the risk of dialysate leakage; a gradual increase in the volume to approximately 30–40 ml/kg (800–1100 ml/m2) may occur as tolerated by the patient. (practice point) 4.2 The initial exchange duration, including inflow, dwell and drain times, should generally be every 60–90 min; gradual prolongation of the dwell time can occur as fluid and solute removal targets are achieved. In neonates and small infants, the cycle duration may need to be reduced to achieve adequate ultrafiltration. (practice point) 4.3 Close monitoring of total fluid intake and output is mandatory with a goal to achieve and maintain normotension and euvolemia. (1B) 4.4 Acute PD should be continuous throughout the full 24-h period for the initial 1–3 days of therapy. (1C) 4.5 Close monitoring of drug dosages and levels, where available, should be conducted when providing acute PD. (practice point) 5. Continuous flow peritoneal dialysis (CFPD) 5.1 Continuous flow peritoneal dialysis can be considered as a PD treatment option when an increase in solute clearance and ultrafiltration is desired but cannot be achieved with standard acute PD. Therapy with this technique should be considered experimental since experience with the therapy is limited. (practice point) 5.2 Continuous flow peritoneal dialysis can be considered for dialysis therapy in children with AKI when the use of only very small fill volumes is preferred (e.g. children with high ventilator pressures). (practice point)

A Novel Formulation of Glucose-Sparing Peritoneal Dialysis Solutions with l-Carnitine Improves Biocompatibility on Human Mesothelial Cells

The main reason why peritoneal dialysis (PD) still has limited use in the management of patients with end-stage renal disease (ESRD) lies in the fact that the currently used glucose-based PD solutions are not completely biocompatible and determine, over time, the degeneration of the peritoneal membrane (PM) and consequent loss of ultrafiltration (UF). Here we evaluated the biocompatibility of a novel formulation of dialytic solutions, in which a substantial amount of glucose is replaced by two osmometabolic agents, xylitol and l-carnitine. The effect of this novel formulation on cell viability, the integrity of the mesothelial barrier and secretion of pro-inflammatory cytokines was evaluated on human mesothelial cells grown on cell culture inserts and exposed to the PD solution only at the apical side, mimicking the condition of a PD dwell. The results were compared to those obtained after exposure to a panel of dialytic solutions commonly used in clinical practice. We report here compelling evidence that this novel formulation shows better performance in terms of higher cell viability, better preservation of the integrity of the mesothelial layer and reduced release of pro-inflammatory cytokines. This new formulation could represent a step forward towards obtaining PD solutions with high biocompatibility.

ISPD guidelines for peritoneal dialysis in acute kidney injury: 2020 update (adults)

Summary statements (1) Peritoneal dialysis (PD) should be considered a suitable modality for treatment of acute kidney injury (AKI) in all settings (1B). Guideline 2: Access and fluid delivery for acute PD in adults (2.1) Flexible peritoneal catheters should be used where resources and expertise exist (1B) (optimal). (2.2) Rigid catheters and improvised catheters using nasogastric tubes and other cavity drainage catheters may be used in resource-poor environments where they may still be life-saving (1C) (minimum standard). (2.3) We recommend catheters should be tunnelled to reduce peritonitis and peri-catheter leak (practice point). (2.4) We recommend that the method of catheter implantation should be based on patient factors and locally available skills (1C). (2.5) PD catheter implantation by appropriately trained nephrologists in patients without contraindications is safe and functional results equate to those inserted surgically (1B). (2.6) Nephrologists should receive training and be permitted to insert PD catheters to ensure timely dialysis in the emergency setting (practice point). (2.7) We recommend, when available, percutaneous catheter insertion by a nephrologist should include assessment with ultrasonography (2C). (2.8) Insertion of PD catheter should take place under complete aseptic conditions using sterile technique (practice point). (2.9) We recommend the use of prophylactic antibiotics prior to PD catheter implantation (1B). (2.10) A closed delivery system with a Y connection should be used (1A) (optimal). In resource poor areas, spiking of bags and makeshift connections may be necessary and can be considered (minimum standard). (2.11) The use of automated or manual PD exchanges are acceptable and this will be dependent on local availability and practices (practice point). Guideline 3: Peritoneal dialysis solutions for acute PD (3.1) In patients who are critically ill, especially those with significant liver dysfunction and marked elevation of lactate levels, bicarbonate containing solutions should be used (1B) (optimal). Where these solutions are not available, the use of lactate containing solutions is an alternative (practice point) (minimum standard). (3.2) Commercially prepared solutions should be used (optimal). However, where resources do not permit this, then locally prepared fluids may be life-saving and with careful observation of sterile preparation procedure, peritonitis rates are not increased (1C) (minimum standard). (3.3) Once potassium levels in the serum fall below 4 mmol/L, potassium should be added to dialysate (using strict sterile technique to prevent infection) or alternatively oral or intravenous potassium should be given to maintain potassium levels at 4 mmol/L or above (1C). (3.4) Potassium levels should be measured daily (optimal). Where these facilities do not exist, we recommend that after 24 h of successful dialysis, one consider adding potassium chloride to achieve a concentration of 4 mmol/L in the dialysate (minimum standard) (practice point). Guideline 4: Prescribing and achieving adequate clearance in acute PD (4.1) Targeting a weekly K t/ V urea of 3.5 provides outcomes comparable to that of daily HD in critically ill patients; targeting higher doses does not improve outcomes (1B). This dose may not be necessary for most patients with AKI and targeting a weekly K t/ V of 2.2 has been shown to be equivalent to higher doses (1B). Tidal automated PD (APD) using 25 L with 70% tidal volume per 24 h shows equivalent survival to continuous venovenous haemodiafiltration with an effluent dose of 23 mL/kg/h (1C). (4.2) Cycle times should be dictated by the clinical circumstances. Short cycle times (1–2 h) are likely to more rapidly correct uraemia, hyperkalaemia, fluid overload and/or metabolic acidosis; however, they may be increased to 4–6 hourly once the above are controlled to reduce costs and facilitate clearance of larger sized solutes (2C). (4.3) The concentration of dextrose should be increased and cycle time reduced to 2 hourly when fluid overload is evident. Once the patient is euvolemic, the dextrose concentration and cycle time should be adjusted to ensure a neutral fluid balance (1C). (4.4) Where resources permit, creatinine, urea, potassium and bicarbonate levels should be measured daily; 24 h K t/ V urea and creatinine clearance measurement is recommended to assess adequacy when clinically indicated (practice point). (4.5) Interruption of dialysis should be considered once the patient is passing >1 L of urine/24 h and there is a spontaneous reduction in creatinine (practice point). The use of peritoneal dialysis (PD) to treat patients with acute kidney injury (AKI) has become more popular among clinicians following evidence of similar outcomes when compared with other extracorporeal therapies. Although it has been extensively used in low-resource environments for many years, there is now a renewed interest in the use of PD to manage patients with AKI (including patients in intensive care units) in higher income countries. Here we present the update of the International Society for Peritoneal Dialysis guidelines for PD in AKI. These guidelines extensively review the available literature and present updated recommendations regarding peritoneal access, dialysis solutions and prescription of dialysis with revised targets of solute clearance.

Exposition to glucose-based peritoneal dialysis fluids exacerbates adipocyte lipolysis and glycogen storage in rat adipose cells

Glucose absorption during peritoneal dialysis (PD) is suspected to promote visceral fat accretion and weight gain in PD patients. The current study was designed to test the impact of glucose-based PD fluids on adipose cell lipolysis and glycogen content. Rat adipose cells, isolated from epididymal fat pad, were exposed to a 30 vol./70 vol. mixture of glucose-based dialysis solutions (containing 1.36% and 3.86% glucose, Physioneal 35®; Baxter) or Krebs–Henseleit buffer for 4 h. Adipose cells were further incubated with laboratory-made solutions containing 1.36% and 3.86% glucose or mannitol as an osmotic control. Baseline and noradrenaline-stimulated lipolysis was measured, and glycogen content assayed. The glucose-based commercial PD fluids as well as the laboratory-manufactured high glucose solutions exacerbated lipolysis in baseline and noradrenaline conditions and increased glycogen stores in adipose cells. Mannitol solutions (1.36% and 3.86%) used as an osmotic control did not produce such effects. This study provides the first evidence that glucose-based dialysis solutions increase basal as well as stimulated lipolysis in adipocytes, an effect that is directly attributable to high concentrations of glucose per se.

P0005TIME-VARYING DIALYSATE BICARBONATE CONCENTRATIONS CAN REDUCE PEAK INTRADIALTIC SERUM BICARBONATE CONCENTRATIONS

Background and Aims Hemodialysis (HD) treatments using bicarbonate-containing dialysis solutions can result in large intradialytic increases in serum bicarbonate concentration, potentially inducing intradialytic alkalemia. It has been suggested that a time-varying, compared with a constant, dialysate bicarbonate concentration may limit the intradialytic increase in serum bicarbonate concentration (Tobvin & Sherman, Semin Dial 2016). We tested this hypothesis using a mathematical model of bicarbonate transport during HD. Method We used the H+ mobilization model describing bicarbonate transport during HD (Sargent et al, Semin Dial 2018) to compare intradialytic serum bicarbonate concentrations when using constant or time-varying dialysate bicarbonate concentrations that deliver the same total amount of buffer base to the patient during the HD treatment. We employed this model to evaluate different time-varying dialysate bicarbonate concentration profiles that started at a high value and then decreased as a step function with a 10-minute timing resolution. Dialysis time was 210 minutes, dialysis solutions were assumed to contain acetate at 3 mEq/L, and all kinetic parameters were assumed to be identical to those reported by Sargent et al (Semin Dial 2018). All results with time-varying dialysate bicarbonate concentrations were compared to a constant dialysate concentration of 32 mEq/L. Results Example results comparing time-varying (36.0 mEq/L for the initial 40 min, 31.2 mEq/L thereafter) and constant (32 mEq/L) dialysate bicarbonate concentrations are shown in the figure. The time-varying dialysate bicarbonate concentration lowered the peak intradialytic serum bicarbonate by 0.4 mEq/L for approximately one-half of the treatment. Similar reductions in the peak intradialytic serum bicarbonate concentration could be achieved if the initial high dialysate bicarbonate concentration was 37.6 mEq/L for 30 min or 40.8 for 20 min. The optimal initial high dialysate bicarbonate concentrations and the reduction in the peak intradialytic serum bicarbonate concentrations were somewhat dependent on the assumed patient-dependent H+ mobilization coefficient. Conclusion We conclude that a time-varying dialysate bicarbonate concentration can lower the peak intradialytic serum bicarbonate concentrations while delivering the same total amount of buffer base to the patient. Whether this approach will yield improved patient outcomes requires further evaluation.