Peritoneal Dialysis Options | IntechOpen
Peritoneal dialysis (PD) is a type of renal substitute remedy used to deal with sufferers with finish‐stage renal illness (ESRD). PD answer is launched by means of a peritoneal catheter within the stomach and changed both by guide exchanges all through the day (steady ambulatory peritoneal dialysis—CAPD) or by a cycler in a single day with or with out daytime exchanges (automated peritoneal dialysis—APD). PD options may be broadly divided into standard PD options and novel options with extra biocompatible traits (e.g. impartial‐pH, low glucose degradation merchandise—GDPs options). The goal of this chapter is to offer an up‐to‐date complete overview of all sorts of PD options which might be at the moment obtainable, together with their influence on affected person‐degree outcomes.
2. Typical PD options
Through the very early days of PD, the composition of PD options assorted broadly from regular saline to five% dextrose . Maxwell and colleagues first developed PD options akin to at the moment used standard PD options . Glucose remains to be getting used as the one osmotic agent in PD options obtainable for medical use. Typical PD options comprise an osmotic agent (i.e. glucose), lactate as a buffer and electrolytes (i.e. Na+, Cl–, Ca2+ and Mg2+) (Desk 1). GDPs, which have been proven to have opposed results on each the peritoneal membrane and systemically, are produced throughout the warmth sterilization course of and/or extended storage. This will probably be mentioned later on this chapter.
2.1. Osmotic agent—glucose
Typical PD options comprise excessive ranges of glucose (dextrose; 75.5–214 mmol/L) as a principal osmotic agent to realize fluid removing (i.e. ultrafiltration throughout the peritoneal membrane). Preparations containing completely different dextrose concentrations (e.g. 0.5 or 0.55%, 1.36 or 1.5%, 2.27 or 2.5% and three.86 or 4.25% for anhydrous or hydrous dextrose, respectively) are routinely obtainable with various osmolalities (345–484 mOsm/L). While glucose is an inexpensive osmotic agent as a result of it’s low cost, simply metabolized, available, simply sterilized and related to a superb lengthy‐time period security profile, the amount of glucose required for efficient ultrafiltration may be problematic. Common systemic glucose absorption from repeated publicity to PD options ranges between 100 and 300 g/day  (equal to 25–75 teaspoons of sugar per day or 36–110 kg/yr), relying on dialysate glucose focus, trade quantity, dwell time and peritoneal transport standing. This considerable peritoneal glucose absorption has in flip been linked with opposed native peritoneal membrane results and systemic metabolic results . Glucose in PD options triggers protein glycosylation and prompts the polyol and protein kinase C pathways [5, 6]. This, together with GDP toxicity and hyperosmolality, probably ends in mesothelial cell dying, peritoneal irritation, neoangiogenesis, epithelial‐to‐mesenchymal transition (EMT), progressive fibrosis and in the end peritoneal membrane failure in continual PD sufferers [7–11]. Systemic glucose absorption has additionally been related to worsening hyperglycaemia in diabetic sufferers, new‐onset hyperglycaemia in incident non‐diabetic PD sufferers, visceral weight problems and dyslipidaemia, characterised by elevated ranges of complete ldl cholesterol, triglyceride, very low‐density lipoprotein (VLDL) and low‐density lipoprotein (LDL) [12–14]. Consequently, the usage of excessive peritoneal glucose concentrations has been related to heightened dangers of cardiovascular and all‐trigger mortality .
A lot of the commercially obtainable standard PD options comprise lactate (30–40 mmol/L) as a buffer and are acidic (pH 5.2–5.5). Lactate diffuses into the bloodstream and is quickly metabolized into bicarbonate. As standard PD options use a single‐chamber supply system, it isn’t attainable to retailer bicarbonate‐buffered options, as calcium and bicarbonate will precipitate to type calcium carbonate. Lactate has been proven to inhibit key mobile features concerned in peritoneal defence mechanisms, together with phagocytosis, bacterial killing and secretion of cytokines .
2.3. Electrolyte composition
The concentrations of Na+, Cl–, Ca2+ and Mg2+ are saved near these of serum concentrations. Removing of those ions is due to this fact virtually utterly depending on convection because of the low diffusion gradient. For a decilitre of fluid eliminated in a 4‐h dwell, roughly 10 mmol of Na+ and 0.1 mmol of Ca2+ are eliminated, on condition that serum Na+ and Ca2+ are inside the reference ranges . Electrolyte concentrations of those options range little by completely different producers. They’re devoid of potassium, and sodium ranges largely vary from 132 to 134 mmol/L. Calcium concentrations vary from 1.00 to 1.75 mmol/L, relying on the producer (Desk 1). Sufferers utilizing calcium‐primarily based phosphate binders are really helpful to make use of PD options with 1.25 mmol/L  calcium focus to scale back the incidence of hypercalcaemia and adynamic bone illness, which have been beforehand related to greater calcium concentrations in PD fluids . The Mg2+ focus is 0.25–0.75 mmol/L. For 1.5% dextrose answer, 0.25 mmol/L is related to zero Mg2+ transport however for greater glucose concentrations there will probably be web Mg2+ losses, which must be saved in thoughts.
2.4. Glucose degradation merchandise
A number of sorts of GDPs are generated throughout the warmth sterilization course of, that are acknowledged to be poisonous at each intra‐peritoneal and systemic ranges [20, 21]. These embody 3‐deoxyglucose, 3,4‐dideoxyglucosone‐3‐ene (3,4‐DGE), 5‐hydroxymethyl furaldehyde, formaldehyde and acetaldehyde. Of the recognized GDPs, 3,4‐DGE is taken into account to be essentially the most dangerous , together with its capacity to lead to dose‐ and time‐dependent renal tubular epithelial cell apoptosis, which raises concern for selling nephrotoxicity from systemic absorption by means of PD . Moreover, varied research have demonstrated opposed results of those GDPs on peritoneal mesothelial cells, fibroblasts, neutrophils and macrophages, together with cytotoxicity, inhibition of proliferation, induction of apoptosis, down‐regulation and disturbance of the homeostatic stability of cytokines, and inhibition of migration, bacterial killing, phagocytosis and respiratory burst in phagocytic cells [24–26]. Additionally they promote peritoneal membrane harm and fibrosis, progressive vasculopathy, altered peritoneal transport traits, impaired host defence towards infections and probably opposed systemic results resembling elevated circulating superior glycation finish merchandise (AGEs) [23, 27, 28].
In abstract, standard PD options are characterised by a number of undesirable traits which were proven to lead to opposed medical outcomes, together with peritoneal membrane damage. Consequently, there was an excellent curiosity in manufacturing newer options with extra ‘biocompatible’ options to be able to mitigate these opposed results. Subsequent sections of this chapter goal to debate the present proof concerning the usage of various kinds of these ‘novel’ PD options and their influence on outcomes.
3. Impartial‐pH, low GDP PD options
Multi‐chamber know-how has led to the event of impartial‐pH, low GDP options. Glucose is separated from different electrolytes in a number of chambers and sterilized at a really low pH (2.8–4.2) to reduce the manufacturing of GDPs. The remaining answer is saved at an alkaline pH (8.0–8.6) within the different compartment. When PD answer must be used, the contents of the 2 compartments are allowed to combine by breaking a lambda seal or a frangible pin, ensuing within the infusion of impartial pH (6.8–7.3), and both a low GDP content material (e.g. Physioneal, Baxter Healthcare) or an ultralow GDP content material (i.e. lower than 80 μmol/L (e.g. Stability or Bicavera, Fresenius Medical Care; Gambrosol Trio, Gambro)) PD answer into the peritoneal cavity. Experimental proof has reported an enchancment in mobile operate (e.g. host immune system and peritoneal mesothelial cells), and higher preservation of peritoneal membrane from publicity to those options . There have been over 20 revealed randomized managed trials (RCTs) evaluating the influence of impartial‐pH, low GDP options on affected person‐degree outcomes , and a few of their key findings will probably be summarized within the following sections.
3.1. Residual renal operate
Therapies utilizing impartial‐pH, low GDP options have been proven to lead to higher preservation of residual renal operate (11 trials, 643 sufferers; standardized imply distinction (SMD) = 0.17 mL/min; 95% confidence interval (CI), 0.01–0.32; p = 0.04) . Furthermore, the profit was evident throughout all comply with‐up durations, extending from lower than 6 months (6 trials, 390 sufferers; SMD: 0.45 mL/min; 95% CI: 0.11–0.79), 6–12 months (9 trials, 568 sufferers; SMD: 0.24 mL/min; 95% CI: 0.08–0.41) and past 12 months in period (5 trials, 279 sufferers; SMD: 0.25 mL/min; 95% CI: 0.01–0.48) . Forest plot from cumulative meta‐evaluation favouring biocompatible PD options is proven in Determine 1.
One potential mechanism underlying attainable good thing about this answer on residual renal operate is diminished systemic absorption of reactive carbonyls (GDPs) from the peritoneal cavity . This might result in diminished systemic publicity to superior glycation finish merchandise (AGEs), which have been proven to exert direct professional‐inflammatory, professional‐apoptotic and professional‐oxidative nephrotoxicity . In response to the rising degree of proof, the Worldwide Society for Peritoneal Dialysis (ISPD) Cardiovascular and Metabolic present tips suggest therapies utilizing impartial‐pH, low GDP PD answer to raised protect residual renal operate in PD sufferers .
3.2. Residual urine quantity
Equally, PD therapy utilizing impartial‐pH, low GDP options has been proven to raised protect residual diuresis (8 trials; 598 sufferers; imply distinction: 127.93 mL/day; 95% CI: 57.54–198.31) . This discovering is additional supported by earlier outcomes from the balANZ trial the place the intervention group skilled a considerably decrease frequency of anuria (7% vs 20%) and an extended time to onset of anuria (p = 0.009) in comparison with the management group receiving standard PD answer [38, 43].
3.3. Peritoneal ultrafiltration
Though there have been issues that a rise in residual diuresis from therapy utilizing these options was a consequence of discount in ultrafiltration, therapies utilizing impartial‐pH, low GDP options haven’t been proven to lead to considerably completely different ultrafiltration when in comparison with standard PD options (7 trials; 571 sufferers; imply distinction: -110.29 mL/day; 95% CI: -311.67 to 91.09) . Though there was no RCT carried out thus far which measured fluid standing objectively (e.g. bioimpedance spectroscopy), medical findings between affected person teams (e.g. physique weight, blood stress) have been proven to be constantly comparable throughout the varied research [38, 41, 44, 45].
3.4. Influx ache
Influx ache, which is reported to happen in as much as 73% of PD sufferers, has been attributed to the acidic pH of standard options . Using impartial‐pH answer seems to successfully alleviate this downside .
The balANZ trial has reported a major profit in lowering peritonitis danger from therapies utilizing impartial‐pH, low GDP PD options, with decrease peritonitis charges (0.30 vs 0.49 episodes per affected person‐yr) and a considerably longer time to the onset of the primary peritonitis episode (p = 0.01) [38, 46]. Moreover, when peritonitis episodes occurred, sufferers within the intervention group skilled milder signs and required shorter hospital period. Though improved peritoneal host defence mechanisms  ensuing from publicity to those options have been thought-about as an underlying mechanism, these outcomes haven’t been equally replicated by different medical trials. Nonetheless, none of those trials, together with the balANZ trial, was designed to guage peritonitis as a main final result measure. Curiously, a meta‐evaluation was in a position to exhibit that a few of the heterogeneity that exists amongst the revealed literature could also be pushed by the excessive prevalence of attrition bias (outlined as drop‐out price >20%), because the balANZ trial was the one one of many six trials assessed to be at a low danger of attrition bias .
3.6. Antagonistic results
In contrast with standard options, biocompatible options haven’t been related to any hurt [30, 47].
So far, there has solely been one financial analysis of impartial‐pH, low GDP PD options in contrast with commonplace options. In a secondary evaluation of the balANZ trial, impartial‐pH, ultralow GDP PD answer was discovered to be a value‐efficient different to straightforward options, primarily on account of discount in peritonitis‐associated hospital prices . Since this time, the prices of biocompatible options have fallen considerably, thereby additional enhancing their value‐effectiveness.
3.8. Different medical outcomes: peritoneal solute transport and clearance, affected person and method survival
So far, therapies utilizing biocompatible options haven’t been proven to exert a major influence on outcomes regarding peritoneal solute transport price, small solute clearance, or affected person and method survival.
PD utilizing impartial‐pH, low GDP PD answer improves clinically essential affected person‐degree outcomes, together with higher preservation of residual renal operate, and residual diuresis with possible profit in the direction of lowering influx ache. There was no recognized improve within the danger of hurt from their use. Furthermore, on account of latest improve within the uptake of those biocompatible options, the price of remedy has been considerably lowered, and is nearly at par with standard therapies. This has allowed for additional improve in uptake within the medical setting.
4. Glucose‐sparing methods
As a result of above‐talked about opposed results of glucose on the peritoneal membrane in addition to its influence on the systemic metabolic degree, there was an excellent curiosity in growing methods for lowering glucose publicity in PD sufferers. From the PD answer perspective, these choices embody common overview of the PD prescription to make sure that the glucose energy of PD answer is suitable and never extreme for a person affected person’s wants. A affected person’s want for peritoneal ultrafiltration (and due to this fact greater peritoneal glucose focus) could also be additional diminished by means of applicable dietary salt and water restriction, administration of diuretics and use of methods to protect residual renal operate (e.g. biocompatible fluids, angiotensin‐changing inhibitors or angiotensin receptor blockers, avoidance of hypotension, and so forth.) [30, 49–53]. A further possibility is to make use of PD options that comprise non‐glucose osmolar brokers, resembling icodextrin.
Icodextrin is a starch‐derived, iso‐osmolar, excessive molecular weight (16,200 Daltons) glucose polymer PD answer. The construction of icodextrin is just like glycogen, consisting of polysaccharide polymers of D‐glucopyranose linked by α‐(1→4) and α‐(1→6) glucosidic bonds. The pharmacokinetics of icodextrin in blood following intra‐peritoneal administration conforms to a easy, single‐compartment mannequin that may be approximated by zero‐order absorption and first‐order elimination . Icodextrin is slowly absorbed by way of the lymphatics and the resultant osmotic gradient dissipates slowly as in comparison with glucose, which is absorbed by way of the small pores of the peritoneal membrane. This gives a lot higher web ultrafiltration throughout the lengthy dwell, particularly in sufferers with excessive transporter standing [55, 56]. Therapy utilizing icodextrin has been proven to realize ultrafiltration equal to fluid removing achieved with 4.25% glucose trade throughout longer PD dwells (10–16 h) . As such, the ISPD, Australian Icodextrin Consensus Working Group and the European Renal Finest Apply (ERBP) Working Group suggest that icodextrin be used for the longer dwell in excessive transporters with web ultrafiltration of lower than 400 mL throughout a 4‐h trade with a 4.25% dextrose answer [57–59]. The worldwide use of icodextrin has expanded past this conventional indication due to accumulating proof of a beneficial profit:hurt profile.
5.1. Results on metabolism: glycaemia and lipid
The glucose‐sparing impact of icodextrin has been proven to lead to an enchancment in metabolic profile primarily based on a number of observational research and RCTs [60–62]. The earliest research to exhibit this was by Johnson et al., who demonstrated important enhancements within the glycaemic management of diabetic PD sufferers handled with icodextrin, whereby HbA1c ranges fell from 8.9 ± 0.7 to 7.9 ± 0.7% . In a subsequent research of 51 diabetic‐prevalent sufferers, the substitute of one in every of glucose‐primarily based PD trade with icodextrin led to important reductions in complete ldl cholesterol, triglyceride and LDL ranges . The reductions had been evident as early as 3 months, though sufferers weren’t allowed to provoke or modify current lipid‐decreasing therapies throughout the research. Equally, Paniagua and colleagues noticed a major discount in fasting glucose, insulin requirement, triglyceride and HbA1c ranges in those that had been randomly assigned to obtain icodextrin (n = 30) of their multi‐centre RCT .
5.2. Ultrafiltration and fluid standing
Icodextrin utilization in a single, day by day PD trade has been proven to extend day by day ultrafiltration (4 trials; 103 sufferers; imply distinction: 448.54 mL/day; 95% CI: 289.28–607.80) and cut back episodes of uncontrolled fluid overload with out compromising residual renal operate (4 trials; 114 sufferers; standardized imply distinction: 0.12, 95% CI: -0.26 to 0.49) . This profit has been proven to be current for all sorts of peritoneal membrane transporters, apart from these with low transport traits . Will increase in fluid removing from prescriptions incorporating icodextrin have been proven to objectively enhance quantity standing measured utilizing bioelectrical impedance , cut back left ventricular mass index , enhance ambulatory blood stress management  and considerably cut back episodes of uncontrolled fluid overload (2 trials; 100 sufferers; relative danger: 0.30; 95% CI: 0.15–0.59) .
5.3. Affected person and method survival
Regardless of advantages regarding metabolic profile and fluid standing, therapies utilizing icodextrin haven’t been proven to enhance method (3 trials; 290 sufferers; relative danger: 0.58; 95% CI: 0.28–1.20) or affected person survival  (6 trials, 816 sufferers; relative danger: 0.82; 95% CI: 0.32–2.13). Nonetheless, nearly all of research included for evaluation (greater than 60%) had comply with‐up durations of lower than 6 months , the place one might argue to be too brief a comply with‐up period to adequately consider these outcomes. This, along with the small pooled pattern measurement from research thus far, signifies that the results of icodextrin on affected person and method survival stay unsure.
5.4. Antagonistic results
Therapies utilizing icodextrin have been proven to extend the serum ranges of its metabolites (i.e. maltose and maltotriose), which peak at 2 weeks after therapy graduation and return to regular ranges after remedy cessation. While the medical significance of those metabolite elevations is unsure, icodextrin is usually really helpful for use in no a couple of trade day by day . The buildup of maltose might result in overestimation of blood glucose ranges on account of interference with glucometers utilizing the glucose dehydrogenase pyrroloquinoline quinone (GDH PQQ) technique, such that sufferers might expertise hypoglycaemia by means of inadvertent extreme insulin administration . Pointers due to this fact suggest that diabetic PD sufferers utilizing icodextrin ought to carry out blood sugar measurements utilizing a glucose‐particular technique (e.g. glucose oxidase or hexokinase reference strategies) . Different potential dangers from icodextrin use embody pores and skin rash, which may result in remedy cessation (0–4.3% of sufferers) , and sterile peritonitis, which thankfully has not been problematic for the reason that introduction of high quality assurance programme monitoring of peptidoglycan ranges .
5.5. Twice day by day icodextrin
Using twice day by day icodextrin (8 h/trade) has been proposed to reap the benefits of its glucose‐sparing traits and excessive ultrafiltration effectivity. Not surprisingly, the research have reported a discount in glucose publicity, higher ultrafiltration and blood stress management with an enchancment in cardiac parameters on echocardiogram [70–73]. Nonetheless, all research thus far had small pattern sizes and brief comply with‐up durations (<6 months). Moreover, the product info of icodextrin nonetheless recommends its use to be restricted as a single trade in every 24‐h interval as inadequate security knowledge can be found on the results of extra frequent administration. Subsequently, the routine use of twice day by day icodextrin can't be really helpful till additional knowledge can be found on security and efficacy.
PD incorporating a single day by day trade of icodextrin ends in considerably greater ultrafiltration, which results in enchancment in quantity standing and cardiac parameters, with out adversely affecting residual renal operate. Though there was no convincing proof to counsel an enchancment in method or affected person survival from its use and icodextrin is extra expensive than standard PD options, the utilization of icodextrin is prone to be a extra value‐efficient possibility in sufferers with ultrafiltration failure than transferring to haemodialysis.
6. Amino acid options
Peritoneal dialysis causes lack of protein and amino acids within the dialysate, which contributes to the event of protein and power malnutrition in these sufferers. Amino acid options had been developed with an goal to compensate for protein loss. These merchandise are osmotically equal to 1.5% glucose PD options, though their use is restricted to a single day by day trade on account of a danger of worsening systemic acidosis and uraemia . Amino acid PD options have been proven to enhance surrogate markers of dietary standing (e.g. insulin‐like development issue‐1, pre‐albumin, transferrin) in malnourished PD sufferers over a 3‐month interval . Nonetheless, a subsequent 3‐yr RCT didn’t present any important influence of amino acid PD answer on hospitalization or mortality in 60 malnourished PD sufferers. Subsequently, the function of amino acid options stays unsure within the absence of proof regarding influence on affected person‐degree medical outcomes.
7. Mixture glucose‐ and GDP‐sparing options
Extra just lately, there was an curiosity in combining icodextrin, amino acid and impartial‐pH, low GDP PD options as a part of glucose‐sparing PD remedy. The newest and the most important RCT carried out was the IMPENDIA‐EDEN research . This was an open‐label, parallel design trial combining two research which in complete randomized 127 sufferers to glucose solely, and 124 to glucose‐sparing therapy group (i.e. one trade of amino acid PD answer, one trade of icodextrin and two exchanges of glucose‐primarily based PD options) for six months. The first final result measure was a change in HbA1c from baseline. Through the research, there was a major lower within the imply HbA1c within the glucose‐sparing arm with a imply distinction of 0.5% between the 2 teams (p = 0.006) . Nonetheless, sufferers within the glucose‐sparing group skilled a considerably greater frequency of great opposed occasions (105 vs 78) and extra deaths (11 vs 5). A big proportion of those occasions had been from fluid overload and hypertensive encephalopathy. This was an sudden final result because the glucose‐sparing group obtained icodextrin, which is understood to extend ultrafiltration. Later, the research investigators hypothesized that some taking part centres tried to overachieve HbA1c discount on the expense of peritoneal ultrafiltration by inappropriately lowering the glucose energy of glucose‐primarily based PD options within the intervention group, which led to this devastating consequence.
In abstract, glucose‐sparing PD remedy has been proven to enhance metabolic profile (i.e. glycaemic management and lipid profile). Nonetheless, there are residual issues about its security, and due to this fact its use can’t be broadly really helpful at current Determine 2.
8. PD options: future
The best PD answer ought to have a physiologic electrolyte and buffer composition and have an osmotic agent that’s non‐poisonous, non‐immunogenic, and never be quickly absorbed into the plasma compartment (or, whether it is, it ought to ideally be quickly metabolized). Moreover, it ought to produce regular osmotic ultrafiltration over the course of a dwell. Thus far, glucose has been the universally used osmotic agent in peritoneal dialysis, primarily based on its relative effectivity, low value, security and fast metabolism in plasma. There was an excellent curiosity in growing new osmotic brokers that meet the above standards. One such new agent is hyperbranched polyglycerol (HPG) , a branched compact polyether polymer (glycidol monomer). As an osmotic agent, HPG fulfills the factors of being supreme in measurement and bodily properties and seems to be non‐poisonous, non‐immunogenic and extremely biocompatible. It may be manufactured with completely different molecular weights so as to add in additional flexibility whether it is to be applied in future medical apply. About 60% is retained within the peritoneum however 25% is excreted in urine. Nonetheless, its lengthy‐time period security, biocompatibility, metabolism and plasma accumulation throughout lengthy‐time period use stays unknown and is at the moment within the preclinical analysis section. Different osmotic brokers, which have been studied, embody L‐carnitine and alanyl‐glutamine, however none of those options are at the moment obtainable for medical use.
One other kind of PD answer at the moment present process additional evaluation is low‐sodium PD options. The rationales for low‐sodium PD answer are (i) to extend absolute sodium removing for a given glucose load and (ii) to scale back the ‘hole’ between sodium and water removing (a consequence of sodium sieving by way of the aquaporin pathway). As quantity homeostasis is a crucial predictor of final result in PD sufferers, a rise in sodium removing by manipulating the sodium focus of PD options to extend web sodium loss is engaging. A number of observational research inspecting various ranges of sodium focus (98–120 mmol/L), both as a single trade or 4 exchanges day by day, have proven a rise in sodium removing, discount in blood stress and a lower in thirst response [78–80]. Nonetheless, the newest multi‐centre, multinational RCT evaluating low‐sodium versus commonplace sodium (125 vs 134 mmol/L) PD answer in hypertensive CAPD sufferers over 6 month comply with‐up period noticed an inferior complete Kt/V with low‐sodium answer (imply distinction -0.78), while peritoneal Kt/V was comparable between the 2 teams. These outcomes had been attributed to a discount in thirst and fluid consumption within the therapy group, probably lowering fluid overload and urine excretion (just like salt‐restricted weight loss plan intervention), which led to a major discount in renal Kt/V within the therapy group. There was a development in the direction of improved blood stress management within the low‐sodium group though extra sufferers developed hyponatraemia than the management group . In gentle of the paucity of proof thus far and the presence of some security alerts, low‐sodium PD options can’t be routinely really helpful for medical apply at this stage.
Not one of the at the moment obtainable PD options is ideal. The PD group wants to stay vigilant in its efforts to develop options which might be extra ‘biocompatible’, ideally utilizing a non‐glucose osmolar agent, which is non‐poisonous, simply metabolized, simply manufactured, value‐efficient and metabolically environment friendly (i.e. predictable ultrafiltration profile with giant ultrafiltration quantity per unit mass absorption). Experimental fashions and worldwide collaboration are required to advance this area of analysis. Within the meantime, individualizing remedy to account for explicit affected person traits is important to enhance medical outcomes.