peritoneal dialysis is a form of kidney dialysis that is used worldwide to treat patients with end stage renal disease ( esrd ) . peritoneal dialysis prevalence varies regionally and , in developed areas , the proportion of dialysis patients on peritoneal dialysis generally ranges between 17 and 36% , although it is as high as 79% in hong kong . peritoneal dialysis removes metabolic waste products and excess water in patients whose kidneys can no longer do so effectively , due to kidney failure . excess water that typically accumulates in esrd patients is removed in peritoneal dialysis by way of ultrafiltration ; water transport into the peritoneal cavity is mostly driven through an osmotic gradient artificially generated by additives to the peritoneal dialysis solution , such as glucose . glucose is readily available , inexpensive , and effective in promoting ultrafiltration of water in esrd patients . decades of use have demonstrated its general efficacy and safety ; however , concerns about the limitations and long - term effects of peritoneal dialysis fluid ( pdf ) glucose , and other factors of the pdf that render it bio - incompatible , have stimulated research and development of alternate dialysis regimens to peritoneal dialysis . the peritoneum is a semipermeable membrane that is composed of a thin layer of connective tissue overlain by a monolayer of mesothelial cells . the peritoneum covers the interior abdominal wall and intra - abdominal organs and has a surface area that approximates body surface area . peritoneal capillaries within the peritoneal membrane interstitium are in relatively close proximity to the mesothelial cell layer , and thus are close to the peritoneal cavity . instillation of pdf into the peritoneal cavity creates solute concentration gradients that lead to the diffusion of highly concentrated  uremic  solutes from the blood supply into the pdf . after time , the pdf becomes saturated with solute and it can be discarded ( drained out through the peritoneal catheter ) , followed by the instillation of fresh dialysate to begin the process anew . standard pdf contains sterile water , electrolytes , lactate ( converted to bicarbonate in vivo ) added as a buffer to treat uremic acidosis , and glucose ( osmotic agent ) . intra - peritoneal glucose is well tolerated by the patient and it is readily metabolized , thus preventing accumulation of toxic by - products . glucose has been used as an osmotic agent in chronic peritoneal dialysis for more than 5 decades . nevertheless , data illuminating the long - term local and systemic effects of glucose - containing pdf continue to accumulate , thus generating concern regarding the metabolic effects of glucose - pdf when used for long periods of time . additionally , the efficacy of peritoneal dialysis , in terms of maintaining sustained ultrafiltration , and the health of the peritoneal membrane itself is thought to be in jeopardy with the long - term use of glucose - pdf . with regards to the effect of glucose - pdf on the peritoneal dialysis system , the major difficulties are twofold ; first , the high concentrations of glucose in pdf are directly cytotoxic to peritoneal mesothelial cells and cause diabetiform changes in the post - capillary venules . the second problem with glucose - pdf involves the effects of standard heat sterilization of pdf during production ; this autoclaving process generates numerous glucose degradation products ( gdps ) in the pdf . additional storage of pdf before use also allows generation of more gdps [ 46 ] . gdps are damaging because they are locally cytotoxic and also glycate local proteins to create advanced glycation end - products ( ages ) . ages are known to be damaging both to the peritoneum and to the body after they enter the systemic circulation from the peritoneal cavity via passive diffusion . a list of gdps commonly found in the peritoneal fluid of peritoneal dialysis patients can be found in table 1 . gdps and ages in pdf are linked to damaging effects on the peritoneal membrane , including mesothelial cell loss , submesothelial fibrosis , calcification , vasculopathy , and diabetiform neoangiogenesis ( implicated as one of the causes of ultrafiltration failure in peritoneal dialysis patients ) . all of these effects cumulatively decrease the effectiveness of the peritoneum as a dialysis membrane , ultimately leading to transfer from peritoneal dialysis to hemodialysis . furthermore , peritoneal gdps and ages entering the circulation are thought to have systemic inflammatory and pro - oxidative effects , and may contribute to advanced atherosclerosis and accelerated loss of residual renal function [ 810 ] ( figure 1 ) . it should be pointed out that , compared with hemodialysis patients , peritoneal dialysis patients typically retain residual renal function longer , often for months to years after the initiation of dialysis . as little as 0.5 ml / min of residual glomerular filtration has been associated with a 12% reduction in the relative risk of death . age , advanced glycosylation end product ; gdp , glucose degradation product ; pd , peritoneal dialysis ; pdf , peritoneal dialysis fluid . the metabolic consequences of glucose - pdf include weight gain , lipid abnormalities , insulin resistance and possibly worsened glycemic control . the glucose content of pdf ranges from 1360 mg / dl to 3860 mg / dl . for a typical patient , pdf glucose is systemically absorbed on the order of about 100 - 300 g of glucose per day and these calories contribute between 12 and 34% of the daily energy intake of peritoneal dialysis patients . in catabolic or uremic patients these may be welcome calories but other patients , who have uncontrolled diabetes , insulin resistance , or obesity , may not benefit from this excess glucose . numerous agents have been investigated as potential alternatives to replace glucose as the osmotic agent in pdf ( e.g. sorbitol , xylitol , mannitol , dextran ) but none have matched the efficacy and relative safety profile of glucose . nevertheless , the bio - incompatibility of standard glucose - pdf has led to continued efforts to develop alternative pdfs that either reduce the level of gdps in dialysate to very low levels , or eliminate glucose entirely , thus preventing gdp formation . pdfs containing amino acid or icodextrin fluid in lieu of glucose are able to be gdp - free , while multi - chambered pdf bags have allowed the production of glucose - pdf with very low levels of gdp . low gdp solution production makes use of the fact that gdp production during heat sterilization is less robust in acidic environments ; manufacturers thus add a small amount of acid to the glucose pdf prior to autoclaving . unfortunately , the resultant acidic solution can not be used directly in the peritoneum because the acidity causes intense pain upon instillation . newer technology has allowed the development of multi - compartment pdf bags where in the glucose component can be heated and stored in a highly acidic environment ( ph 2.6 - 3 ) while the remainder of the pdfs ( containing electrolytes and buffer ) are in a separate compartment at a higher ph ; the two compartments are mixed just prior to use and , in doing so , achieve a more physiologic ph and excellent patient tolerability intraperitoneally . pdfs since they contain fewer gdps than standard pdfs ; for example , they can achieve 3-deoxyglucosone concentrations less than 66 . amino acid solution is a pdf that eliminates gdp entirely by substituting amino acid in lieu of glucose as the osmotic agent . earlier formulations of amino acid solution were associated with marked metabolic acidosis and adverse nutritional effects ; subsequent iterations of amino acid solution , with a higher concentration of buffer , have generally been better tolerated but are still associated with acidosis and are poorly tolerated when used more than once daily . icodextrin is another osmotic agent used in pdf to replace glucose ; icodextrin is a starch - derived poly - glucose molecule that induces water transport into the peritoneal cavity via colloid forces . icodextrin has a high peritoneal membrane reflection coefficient , and therefore remains in situ for long periods of time , thus enabling sustained ultrafiltration . it slowly exits the peritoneal cavity via lymphatic channels ( it is not readily absorbed by the peritoneum ) , and is subsequently metabolized intracellularly . although its metabolism does lead to energy absorption ( i.e. carbohydrate calories ) , the metabolic profile of patients using icodextrin appears to be superior to that achieved with glucose - only pdf . a summary of data obtained from in vitro , in vivo , experimental and clinical studies with biocompatible pdfs is found in table 2 . in general , biocompatible fluids appear to better preserve the peritoneum , reduce the formation of local age , and attenuate the development of peritoneal vasculopathy compared with standard glucose - pdf . clinical studies on the subject have recently been evaluated in a cochrane review ; the authors concluded that data from the available studies ( all of sub - optimal quality ) show that neutral ph , low gdp pdf increases urine output after 12 months of use . of note , decreased peritoneal ultrafiltration rates appear to accompany increased urine output in these studies , suggesting that increased urine output may result from a shift in the location of water transport ( from peritoneum to kidney ) rather than improved renal function per se . a recent meta - analysis of studies examining the effect of neutral ph , low gdp solution on residual renal function was unable to find a significant benefit . there is no definitive benefit of newer solutions on peritonitis rates ; an equal number of studies show no difference in rates with newer pdf as show a benefit with biocompatible pdf . finally , there has been no good trial to date to show a survival benefit with the use of biocompatible or glucose - sparing pdf . age , advanced glycosylation end product ; crp , c - reactive protein ; gdp , glucose degradation product ; interleukin , il . a prospective crossover trial in 22 diabetic peritoneal dialysis patients substituted one glucose - pdf exchange per day with either one amino acid solution or one icodextrin exchange , for a period of 8 weeks . serum triglyceride levels decreased with both amino acid solution and icodextrin compared with glucose - pdf , and free fatty acids decreased during the use of amino acid solution . a larger trial performed in mexico prospectively evaluated the effect of one icodextrin per day versus standard pdf in 59 diabetic peritoneal dialysis patients . compared to baseline , the icodextrin group ( but not the control group ) had reduced insulin need , lower fasting glucose , lower serum triglyceride level , lower hemoglobin ( hgb)a1c , and fewer adverse events related to glucose control . more recently , the impendia and eden trials evaluated the clinical effects of a glucose - sparing peritoneal dialysis regimen in a multi - national study involving 251 peritoneal dialysis patients who were randomized to a glucose - sparing regimen or control group ( table 3 ) . baseline mean hgba1c was not statistically different between the two groups ( 7.6% in control , 7.7% in intervention ) . the main finding was an improvement in the mean glycated hgb in the intervention group but not in the control group , in the order of a 0.5% improvement in 6 months ( hba1c decreased from 7.7 to 7.2% during the 6 months of study treatment ) . secondary positive findings included a significant reduction in very low density lipoprotein , serum triglyceride and apolipoprotein b levels , as well as a trend towards a greater decrease in visceral fat volume in the intervention group . unfortunately , over the 6-month study time , there was an unexpected decrease in mean serum albumin in the intervention group ( -0.5 g / l ) compared with an increased serum albumin in the control group ( 0.6 g / dl ) . there were also more reported deaths in the intervention group than control ( 11 versus 5 ) , although these were all considered unrelated to the study as judged by a study panel . overall there was a significantly higher incidence of treatment - related adverse events , serious adverse events , and hypoglycemia , and more episodes of volume overload in the intervention group , plus a higher number of patients in the intervention group withdrew from the study . it is not easy to organize a large multi - center trial in peritoneal dialysis , and it is disappointing that such an effort found a glucose - sparing peritoneal dialysis regimen to have more adverse events ( particularly fluid overload ) than a traditional glucose - only peritoneal dialysis regimen , despite metabolic benefits in the former . nevertheless , we must consider that the trial was not performed in a tightly controlled experimental environment , but rather in many centers spanning 11 different countries , where local physician practice dictated volume management , and where these practices were by no means standardized . fewer adverse events might well be seen with glucose - sparing regimens if close monitoring of fluid status is upheld , and prompt changes are made to the peritoneal dialysis regimen when needed . perhaps simply substituting a glucose bag for a non - glucose bag in a 1:1 fashion is not the answer ; glucose - sparing regimens likely require additional adjustments to sustain adequate daily ultrafiltration . as an example , several studies have shown less peritoneal ultrafiltration with biocompatible pdf than standard glucose - pdf ; when one biocompatible exchange is substituted for one glucose - pdf , the patient may require higher osmolality in one or all of the remaining standard - pdfs to reach daily ultrafiltration targets . many more questions than answers exist at this time regarding the role of biocompatible pdf and glucose - sparing regimens in chronic peritoneal dialysis . some suggestions for future investigation are provided below : ( a ) does glucose sparing improve the long - term use of the peritoneal dialysis technique ? ( b ) does glucose sparing in non - diabetics who start peritoneal dialysis improve outcomes ? ( c ) how strictly should blood sugar be controlled in peritoneal dialysis patients , and do blood sugar targets vary for different subgroups of peritoneal dialysis patients ? ( d ) in diabetic peritoneal dialysis patients , what is the effect of glucose sparing on microvascular complications of diabetes ( e.g. retinopathy , non - traumatic amputation ) ? ( e ) in diabetic peritoneal dialysis patients , what is the long - term effect of glucose sparing on macrovascular complications of diabetes , including atherosclerotic cardiovascular disease ?