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• W2016605436 abstract "Since the widespread introduction of peritoneal dialysis (PD) into the standard care of patients with chronic kidney disease there has been a shift from the initial focus on technique survival to refinement of the therapy to enhance biocompatibility and improve both the local peritoneal and systemic consequences of PD. One of the most significant contributions to these advances has been the development of novel PD solutions. The use of new manufacturing techniques, buffer presentation, and new osmotic alternatives to glucose have allowed potentially improved peritoneal survival (in terms of structure and function) and improved subjective patient experience. Additional benefits have also included, enhanced management of salt and water removal, supported nutritional status and improvement in the systemic metabolic derangements associated with conventional PD treatment, based on glucose-containing lactate-buffered solutions. The selection of suitable targets for modulation of therapy continues to be hampered by our continued relative ignorance of the local and particularly systemic effects of PD compounded by the dearth of quality, outcome-based studies. The aim of this review is to summarize the characteristics of the next generation of PD fluids currently available, and then to evaluate their possible place in treatment by considering the difference in their effects in a series of structural and functional areas potentially relevant to improving patient outcomes. Since the widespread introduction of peritoneal dialysis (PD) into the standard care of patients with chronic kidney disease there has been a shift from the initial focus on technique survival to refinement of the therapy to enhance biocompatibility and improve both the local peritoneal and systemic consequences of PD. One of the most significant contributions to these advances has been the development of novel PD solutions. The use of new manufacturing techniques, buffer presentation, and new osmotic alternatives to glucose have allowed potentially improved peritoneal survival (in terms of structure and function) and improved subjective patient experience. Additional benefits have also included, enhanced management of salt and water removal, supported nutritional status and improvement in the systemic metabolic derangements associated with conventional PD treatment, based on glucose-containing lactate-buffered solutions. The selection of suitable targets for modulation of therapy continues to be hampered by our continued relative ignorance of the local and particularly systemic effects of PD compounded by the dearth of quality, outcome-based studies. The aim of this review is to summarize the characteristics of the next generation of PD fluids currently available, and then to evaluate their possible place in treatment by considering the difference in their effects in a series of structural and functional areas potentially relevant to improving patient outcomes. The choices made in the design of conventional peritoneal dialysis (PD) fluids were based on attempting to mimic normal plasma, tempered by a series of compromises to allow production, and ultimate stability under storage conditions of the fluids. These imperatives resulted in glucose being used as the main osmotic agent, buffered with lactate alone (to produce a low pH). This allowed sterilization of the fluids by heat and avoid caramalization of the glucose. The use of glucose in PD fluid (and in particular the higher concentrations required to provide enhanced ultrafiltration) has direct deleterious effects on peritoneal structure (diabetiform change)1.Feriani M. Buffers: bicarbonate, lactate and pyruvate.Kidney Int. 1996; 56: S75-S80Google Scholar,2.Di Paolo N. Sacchi G. Peritoneal vascular changes in continuous ambulatory peritoneal dialysis (CAPD): an in vivo model for the study of microangiopathy.Perit Dial Bull. 1985; 9: 41-45Google Scholar and function. Low pH results in increased infusion pain3.Mactier R.A. Sprosen T.S. Gokal R. et al.Bicarbonate and bicarbonate/lactate peritoneal dialysis solutions for the treatment of infusion pain.Kidney Int. 1998; 53: 1061-1067Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar and directly effects neoangiogenesis and mesothelial cell damage.4.Hoff C.M. In vitro biocompatibility performance of physioneal.Kidney Int Suppl. 2003; 88: S57-S74Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar In combination with the commercial manufacturing process these factors also result in the production of glucose degradation products (GDPs).5.Witowski J. Jorres A. Korybalska K. et al.Glucose degradation products in peritoneal dialysis fluids: do they harm?.Kidney Int Suppl. 2003; 84: S148-S151Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar These possess well-defined local toxicities to the peritoneal membrane and are also systemically absorbed (with a range of currently inadequately defined biological effects). GDPs also enhance the local and systemic production of advanced glycation end products by the reaction of the aldehyde form of glucose, in the presence of amines or proteins, to produce Amadori glycosolation products.6.Pischetsreider M. Chemistry of glucose and biochemical pathways of biological interest.Perit Dial Int. 2000; 20: S26-S30PubMed Google Scholar Advanced glycation end product accumulation has been implicated in the development of structural damage of the peritoneum and vasculature.7.Krediet R.T. Zweers M.M. van der Wal A.C. et al.Neoangiogenesis in the peritoneal membrane.Perit Dial Int. 2000; 20: S19-S25PubMed Google Scholar The newer generations of PD solutions have sought to utilize more physiological intraperitoneal pH, and reduce GDP production by a combination of this reduced pH with improved manufacturing and product presentation. The choice of glucose alternatives further reduces the potential to generate GDPs. Enhanced biocompatibility is achieved to varying degrees depending on the approaches used. The avoidance of hypertonic glucose itself has emerged as a therapeutic aim for both local peritoneal and systemic exposure reasons. The use of alternatives that are absorbed (amino acids) has also been developed to enhance nutrition in depleted patients. There are two main groups of products currently commercially available. Multibag systems separate out the buffer (either lactate or bicarbonate/lactate mix). This allows the glucose to be stored at a low pH and minimizes degradation during protracted storage.8.Passlick-Deetjen J. Lage C. Lactate-buffered and bicarbonate-buffered solutions with less glucose degradation products in a two-chamber system.Perit Dial Int. 2000; 20: S42-S47PubMed Google Scholar It also prevents the precipitation that would result in the mixing of a bicarbonate buffer and magnesium and calcium in solution. Both Baxter and Fresenius produce two bag systems resulting in a more physiological intraperitoneal pH. Physioneal® fluids from Baxter utilize a lactate/bicarbonate mixed buffer (ph 7–7.4). The use of bicarbonate/lactate mix (25 mmol/l bicarbonate with 15 mmol/l lactate) was favored over pure bicarbonate buffering owing to lower infusion pain scoring.3.Mactier R.A. Sprosen T.S. Gokal R. et al.Bicarbonate and bicarbonate/lactate peritoneal dialysis solutions for the treatment of infusion pain.Kidney Int. 1998; 53: 1061-1067Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar The Fresenius Stay Safe Balance® system separates glucose and electrolytes from a lactate buffer and results in a neutral pH once mixed. The bicaVera® system utilizes a pure bicarbonate buffer (34 mmol/l), which although does not result in a more physiological pH, does avoid potentially deleterious local effects attributable to lactate. Gambro produce Gambrosol Trio® (a lactate-buffered three bag system) which also separates the hypertonic glucose component, allowing a solution of differing tonicity to be mixed before use, depending on the ultimate combination of compartments performed. Although lactate buffered this still results in a higher pH than characteristically seen with earlier generation low biocompatibility solutions (pH 6.5 c.f. 5.5). There are currently no quality data comparing these newer generation of lower GDP-containing glucose-based solutions against each other in clinical practice. The second group consist of alternatives to glucose as an osmotic agent. Baxter market Extraneal® (7.5% icodextrin). This contains a glucose polymer that is only absorbed after having undergone a degree intraperitoneal hydrolysis (ultimately to maltose). Currently this is buffered with lactate alone (although a lactate/bicarbonate-buffered alternative is undergoing formal clinical evaluation), and has a lower GDP content than conventional PD fluids.9.Cooker L.A. Choo C.G. Luneburg P. et al.Effect of icodextrin peritoneal dialysis solution on cell proliferation in vitro.Adv Perit Dial. 1999; 15: 17-20PubMed Google Scholar This provides an ultrafiltration capacity broadly similar to 2.27% glucose-containing solutions, but owing to a reduced back diffusion from intraperitoneal cavity into the circulation allows longer sustained ultrafiltration, particularly suited to long dwells.10.Ho-dac-Pannekeet M.M. Schouten N. Langendijk M.J. et al.Peritoneal transport characteristics with glucose polymer based dialysate.Kidney Int. 1996; 50: 979-986Abstract Full Text PDF PubMed Scopus (157) Google Scholar Concerns about higher levels of circulating maltose limit use of these solutions to a single daily exchange. Hypersensitivity can occur.11.Frampton J.E. Plosker G.L. Icodextrin: a review of its use in peritoneal dialysis.Drugs. 2003; 63: 2079-2105Crossref PubMed Scopus (67) Google Scholar Baxter also produces Nutrineal® (1.1% amino-acid-containing solution). This is presented as a single bag lactate-buffered fluid (40 mmol/l) and has the equivalent ultrafiltration capacity of 1.36% glucose-containing fluids. It's use further avoids glucose exposure, and contains no GDPs. It has been demonstrated to enhance nutrition in hypoalbuminemic continuous ambulatory peritoneal dialysis patients,12.Taylor G.S. Patel V. Spencer S. et al.Long-term use of 1.1% amino acid dialysis solution in hypoalbuminemic continuous ambulatory peritoneal dialysis patients.Clin Nephrol. 2002; 58: 445-450Crossref PubMed Google Scholar but is also limited to single daily use owing to the potential for increased symptomatic uremia and acidosis with increased exposure.13.Chen C.J. Moberly J.B. Martis L. New developments in peritoneal dialysis solutions.Adv Perit Dial. 1998; 14: 116-119PubMed Google Scholar The majority of direct toxicity to the peritoneum appears to be attributable to GDPs rather than pH, lactate, osmolality, or glucose per se. A variety of GDPs are characteristically formed but they appear to have differing toxic potential.14.Catalan M.P. Santamaria B. Reyero A. et al.3,4-di-deoxyglucosone-3-ene promotes leukocyte apoptosis.Kidney Int. 2005; 68: 1303-1311Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar Mesothelial toxicity is attributable both directly to GDPs and as a result of local advanced glycation end product formation.15.Welten A.G. Schalkwijk C.G. ter Wee P.M. et al.Single exposure of mesothelial cells to glucose degradation products (GDPs) yields early advanced glycation end-products (AGEs) and a proinflammatory response.Perit Dial Int. 2003; 23: 213-221PubMed Google Scholar advanced glycation end products accumulate in the peritoneal membrane and contribute to angiogenesis and subsequent diabetiform change.16.Nakayama M. Kawaguchi Y. Yamada K. et al.Immunohistochemical detection of advanced glycosylation end-products in the peritoneum and its possible pathophysiological role in CAPD.Kidney Int. 1997; 51: 182-186Abstract Full Text PDF PubMed Scopus (276) Google Scholar Use of low GDP-containing solution (Fresenius Balance®) was associated with improved viability and proliferation of mesothelial cells, as evidenced by increased levels of Ca-125 and fibronectin in peritoneal effluent, in medium comparative study against conventional PD fluids.17.Witowski J. Korybalska K. Ksiazek K. et al.Peritoneal dialysis with solutions low in glucose degradation products is associated with improved biocompatibility profile towards peritoneal mesothelial cells.Nephrol Dial Transplant. 2004; 19: 917-924Crossref PubMed Scopus (61) Google Scholar Experimental data also suggest that lower GDP-containing solutions are associated with improved mesothelial-based healing.18.Morgan L.W. Wieslander A. Davies M. et al.Glucose degradation products (GDP) retard remesothelialization independently of D-glucose concentration.Kidney Int. 2003; 64: 1854-1866Abstract Full Text Full Text PDF PubMed Scopus (91) Google Scholar Similar effects have also been reported with other low GDP-containing glucose-based fluids. Extraneal® usage compared to higher hypertonic glucose exposure has also been demonstrated to be associated with improved preservation of peritoneal function.19.Davies S.J. Brown E.A. Frandsen N.E. et al.Longitudinal membrane function in functionally anuric patients treated with APD: data from EAPOS on the effects of glucose and icodextrin prescription.Kidney Int. 2005; 67: 1609-1615Abstract Full Text Full Text PDF PubMed Scopus (139) Google Scholar Nutrineal® has been inadequately evaluated in man in this respect, but some data exist that suggest that it has a similarly protective effective on the peritoneum.20.Martikainen T.A. Teppo A.M. Gronhagen-Riska C. et al.Glucose-free dialysis solutions: inductors of inflammation or preservers of peritoneal membrane?.Perit Dial Int. 2005; 25: 453-460PubMed Google Scholar Low GDP-containing solutions also appear to reduce intraperitoneal inflammation21.Fusshoeller A. Plail M. Grabensee B. et al.Biocompatibility pattern of a bicarbonate/lactate-buffered peritoneal dialysis fluid in APD: a prospective, randomized study.Nephrol Dial Transplant. 2004; 19: 2101-2106Crossref PubMed Scopus (75) Google Scholar and be associated with better maintenance of macrophage function. Whether or not these effects are associated with reduced peritonitis rates is still awaiting robust randomized controlled trial-based study. However data from registry sources suggests that peritonitis rate was significantly reduced in patients receiving Physioneal® compared to standard PD solutions.22.Van Bree M. Miseraque D. Story K.O. et al.J Am Soc Nephrol. 2002; 13: S43AGoogle Scholar Use of Physioneal® is certainly associated with reduced infusion pain3.Mactier R.A. Sprosen T.S. Gokal R. et al.Bicarbonate and bicarbonate/lactate peritoneal dialysis solutions for the treatment of infusion pain.Kidney Int. 1998; 53: 1061-1067Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar and improved sleep when used as a part of an automated PD regimen.23.Dratwa M. Wilkie M. Ryckelynck J.P. et al.Clinical experience with two physiologic bicarbonate/lactate peritoneal dialysis solutions in automated peritoneal dialysis.Kidney Int Suppl. 2003; 88: S105-S113Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar The adequate control of total body water and sodium are key therapeutic targets for effective renal replacement therapy. Failure to do so leads to hypertension and chronic volume overload. These effects on left ventricular mass have been well established as being an independent cardiovascular risk factor in this patient group.24.Harnett J.D. Foley R.N. Kent G.M. et al.Congestive heart failure in dialysis patients: prevalence, incidence, prognosis and risk factors.Kidney Int. 1995; 47: 884-890Abstract Full Text PDF PubMed Scopus (547) Google Scholar The two key elements to achieving this in PD patients are the effects of the dialysis solution itself on sustained ultrafiltration, and any effects on the maintenance of residual renal function (RRF) (Tables 1 and 2).Table 1Summary of the characteristics of currently widely available multibag PD solutionsManufacturerPotential drawbacksPotential benefitsLactate buffered Balance® Gambrosol Trio®Fresenius GambroMore physiological pH, but not neutralLocal and systemic glucose exposureLower GDP levelsMore physiological pHImproved peritoneal membrane biocompatibilityPreserved membrane defenceLactate/bicarbonate buffered Physioneal®BaxterLocal and systemic glucose exposureDoes not eliminate peritoneal lactate exposureLower GDP levelsMore physiological pHImproved peritoneal membrane biocompatibilityPreserved membrane defenceReduced infusion painBicarbonate buffered BicaVera®FreseniusLocal and systemic glucose exposureLower GDP levelsMore physiological pHImproved peritoneal membrane biocompatibilityPreserved membrane defenceImproved correction of acidosisGDP, glucose degradation product; PD, peritoneal dialysis. Open table in a new tab Table 2Summary of the characteristics of currently widely available single bag PD solutionsManufacturerPotential drawbacksPotential BenefitsLactate-buffered glucose containing Dianeal®BaxterLow pHHigh GDP contentPoor peritoneal membrane biocompatibilityInfusion painLocal and systemic glucose exposureEase of manufactureLow costIcodextrin-containing Lactate bufferedBaxterHypersensitivityLow pHLicensed for single daily use onlyLactate containingSustained ultrafiltrationPreservation of RRFHypertonic glucose replacementReduced hyperglycemiaImproved short term systemic hemodynamic profileDesirable effects on metabolic profile and body compositionAmino-acid containing Nutrineal®BaxterLow pHLicensed for single daily use only (avoid exacerbation of uremic symptoms and acidosis)No GDPsAvoid systemic and peritoneal glucose exposurePeritoneal membrane protectionEnhance nutritionGDP, glucose degradation product; PD, peritoneal dialysis; RRF, residual renal function. Open table in a new tab GDP, glucose degradation product; PD, peritoneal dialysis. GDP, glucose degradation product; PD, peritoneal dialysis; RRF, residual renal function. The use of icodextrin-based fluids is associated with an improved fluid status in prospective study.25.Davies S.J. Woodrow G. Donovan K. et al.Icodextrin improves the fluid status of peritoneal dialysis patients: results of a double-blind randomized controlled trial.J Am Soc Nephrol. 2003; 14: 2338-2344Crossref PubMed Scopus (286) Google Scholar Extracellular water and total body water were better controlled compared to patients relying exclusively on the use of high glucose concentration fluids. Icodextrin was also associated with better maintenance of residual urine output. Earlier reports that icodextrin use is associated with a more rapid loss of RRF appear to be owing to the effects of inappropriate fluid reduction in a small sub group of patients, resulting in a clinical underhydration.26.Konings C.J. Kooman J.P. Gladziwa U. et al.A decline in residual glomerular filtration during the use of icodextrin may be due to underhydration.Kidney Int. 2005; 67: 1190-1191Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar Icodextrin use is also associated with an increased mass transfer area coefficient and an increased convective contribution to small solute and free water removal.27.Asghar R.B. Diskin A.M. Spanel P. et al.Influence of convection on the diffusive transport and sieving of water and small solutes across the peritoneal membrane.J Am Soc Nephrol. 2005; 16: 437-443Crossref PubMed Scopus (18) Google Scholar Low sodium dialysate, to enhance diffusive removal, is currently under evaluation. Results are not yet available form this therapeutic approach. Initial study of bicarbonate/lactate-buffered PD solutions suggested that net ultrafiltration at peritoneal equilibration test after 6-month follow-up was higher than with conventional-buffered glucose-containing fluid usage.28.Tranaeus A. A long-term study of a bicarbonate/lactate-based peritoneal dialysis solution – clinical benefits. The Bicarbonate/Lactate Study Group.Perit Dial Int. 2000; 20: 516-523Abstract Full Text Full Text PDF PubMed Scopus (154) Google Scholar A combination of bicarbonate/lactate-buffered solutions with icodextrin and amino-acid-containing fluids, when studied against conventional fluids, resulted in a lesser reduction in residual creatinine clearance, after 6 months of use. However this effect on RRF was not seen consistently throughout all components of the study, and some differences in RRF between the groups did exist on inclusion. The overall effects of fluid biocompatibility c.f. glucose exposure reduction is not possible to determine from this study.29.le Poole C.Y. van Ittersum F.J. Weijmer M.C. et al.Clinical effects of a peritoneal dialysis regimen low in glucose in new peritoneal dialysis patients: a randomized crossover study.Adv Perit Dial. 2004; 20: 170-176PubMed Google Scholar The GDP, 3,4-dideoxyglucosone-3-ene is toxic to cultured tubular cells at biologically relevant concentrations,30.Justo P. Sanz A.B. Egido J. et al.3,4-Dideoxyglucosone-3-ene induces apoptosis in renal tubular epithelial cells.Diabetes. 2005; 54: 2424-2429Crossref PubMed Scopus (82) Google Scholar and this may be a potential mechanism in RRF loss. Other than the modulation of overall hydration, the effects that PD fluids are capable of having beyond the membrane are largely determined by the absorption of the osmotic agent (glucose or amino acids) and the systemic exposure to GDPs. These effects result in profound metabolic, body compositional, lipid, endocrine, and cardiovascular structural/ functional perturbations. Intraperitoneal glucose exposure is associated with poorer glycemic control in diabetic continuous ambulatory peritoneal dialysis patients. Substitution of glucose-based conventional fluids for a regimen based on bicarbonate/lactate buffered 1.36% glucose, icodextrin and amino-acid-based solutions resulted in improved blood glucose levels and a reduction in hyperglycemic excursions. The use of similar glucose exposure in a more biocompatible Physioneal® format c.f. standard solutions was also associated with a small improvement in mean blood glucose levels.31.Marshall J. Jennings P. Scott A. et al.Glycemic control in diabetic CAPD patients assessed by continuous glucose monitoring system (CGMS).Kidney Int. 2003; 64: 1480-1486Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar The mechanisms for this are unknown. Intraperitoneal glucose exposure results in significant amounts of absorption. This results in loss of the osmotic gradient (with impaired ultrafiltration). Furthermore higher glucose concentration use also results in hyperglycemia with associated hyperinsulinemia (even in non-diabetic patients).32.Delarue J. Maingourd C. Acute metabolic effects of dialysis fluids during CAPD.Am J Kidney Dis. 2001; 37: S103-S107Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar Hyperinsulinemia is a well-recognized additional cardiovascular risk factor. It is also associated with systemic cardiovascular functional changes and results in increased stroke volume with a significant hypertensive response. These changes seen with hypertonic glucose are not related to alterations in cardiac filling.33.Selby N.M. Fialova J. McIntyre C.W. The systemic haemodynamic and metabolic effects of peritoneal dialysis fluids.Nephrol Dial Transplant. 2006Google Scholar In the longer term the increased carbohydrate load also predisposes to abnormalities of lipid metabolism, and increased insulin resistance. The substitution of hypertonic glucose with icodextrin appears to be capable of ameliorating these effects.34.Bredie S.J. Bosch F.H. Demacker P.N. et al.Effects of peritoneal dialysis with an overnight icodextrin dwell on parameters of glucose and lipid metabolism.Perit Dial Int. 2001; 21: 275-281PubMed Google Scholar Use of higher concentrations of glucose in PD regimens is associated with an increase in drained body weight, as a result of increased fat mass.25.Davies S.J. Woodrow G. Donovan K. et al.Icodextrin improves the fluid status of peritoneal dialysis patients: results of a double-blind randomized controlled trial.J Am Soc Nephrol. 2003; 14: 2338-2344Crossref PubMed Scopus (286) Google Scholar Avoidance of hypertonic glucose, with substitution by either icodextrin or amino-acid-based PD fluids, has been reported to abrogate most of these effects. Patients with chronic kidney disease exhibit muscle wasting,35.McIntyre C.W. Selby N.M. Sigrist M. et al.Patients receiving maintenance dialysis have more severe functionally significant skeletal muscle wasting than patients with dialysis-independent chronic kidney disease.Nephrol Dial Transplant. 2006; 8: 2210-2216Crossref Scopus (118) Google Scholar and this is associated with poorer long-term outcomes. PD patients exhibit greater degrees of muscle mass loss over a 12 month follow-up period than chronic kidney disease 4 or established hemodialysis patients of similar dialysis vintage.36.McIntyre C.W. Sigrist M. Selby N.M. Functionally significant progressive skeletal muscle wasting in CKD 4 and CKD 5 (PD and HD) patients.. 2005; 16 (ASN PO832): 301AGoogle Scholar Furthermore, initiation of dialysis with PD resulted in a greater incremental decline in functionally significant muscle mass than those commencing hemodialysis. Patients with PD regimens with a higher exposure to glucose had proportionately more muscle wasting and increased fat accumulation than those with lower weekly glucose exposure. This may be as a result of altered intramuscular insulin-like growth factor signalling in the setting of hyperinsulinemia. Whether or not this is amenable to glucose substitution awaits further prospective study. Amino-acid-containing PD solution usage increases muscular amino-acid utilization37.Delarue J. Maingourd C. Objois M. et al.Effects of an amino acid dialysate on leucine metabolism in continuous ambulatory peritoneal dialysis patients.Kidney Int. 1999; 56: 1934-1943Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar and is related to an increase in serum albumin, in short to medium term study of hypoalbuminemic PD patients.38.Kopple J.D. Bernard D. Messana J. et al.Treatment of malnourished CAPD patients with an amino acid based dialysate.Kidney Int. 1995; 47: 1148-1157Abstract Full Text PDF PubMed Scopus (202) Google Scholar Whether or not this is capable of meaningfully retaining muscle mass and improving outcomes in malnourished PD patients has not been directly studied. The undesirable cardiovascular status of PD patients is further worsened by a deleterious increase in serum leptin and relative reduction in adiponectin.39.Perez-Fontan M. Cordido F. Rodriguez-Carmona A. et al.Acute plasma ghrelin and leptin responses to oral feeding or intraperitoneal hypertonic glucose-based dialysate in patients with chronic renal failure.Kidney Int. 2005; 68: 2877-2885Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar These are modulated by visceral fat in particular, but significant changes occur early after therapy initiation before significant changes in body composition.40.Kim D.J. Oh D.J. Kim B. et al.The effect of continuous ambulatory peritoneal dialysis on change in serum leptin.Perit Dial Int. 1999; 19: S172-S175PubMed Google Scholar In vitro work has suggested that high glucose PD fluids are capable of directly modulating adipokine release from adipocytes41.Teta D. Tedjani A. Burnier M. et al.Glucose-containing peritoneal dialysis fluids regulate leptin secretion from 3T3-L1 adipocytes.Nephrol Dial Transplant. 2005; 20: 1329-1335Crossref PubMed Scopus (21) Google Scholar and use of glucose-free alternatives may modulate these levels in vivo.42.Furuya R. Odamaki M. Kumagai H. et al.Beneficial effects of icodextrin on plasma level of adipocytokines in peritoneal dialysis patients.Nephrol Dial Transplant. 2006; 21: 494-498Crossref PubMed Scopus (56) Google Scholar Vascular calcification is increasingly appreciated as being an important driver of cardiovascular mortality in chronic kidney disease patients. PD is associated with a lower calcification burden as compared with matched hemodialysis patients.43.Sigrist M. Bungay P. Taal M.W. McIntyre C.W. Vascular calcification and cardiovascular function in chronic kidney disease.Nephrol Dial Transplant. 2006; 21: 707-714Crossref PubMed Scopus (166) Google Scholar Indeed progression over a 1-year period was similar to that seen in chronic kidney disease 4 patients, and significantly less than those on hemodialysis. These changes in peripheral vascular calcification were proportional to changes in arterial stiffness over the corresponding period.44.Sigrist M. Bungay P. McIntyre C.W. Functionally significant vascular calcification is rapidly progressive in CKD 4 and 5 patients.. 2005; 16 (ASN PO311): 187AGoogle Scholar Multivariate assessment of the factors associated with the change in calcification score revealed that not only dialysis modality was important, but also a maintained ability to eliminate calcium. Maintenance of RRF and sustained peritoneal removal of calcium (highly dependant on ultrafiltration volumes) may be important.45.Sigrist M. Bungay P. McIntyre C.W. Determinants of progressive vascular calcification in CKD 4 and 5 patients.. 2006; 17 (Abstract submitted ASN): 507AGoogle Scholar Use of icodextrin-based fluids may have an advantage in this respect over conventional choices. Serum phosphate is also a major risk factor in the development of arterial calcification. Provision of dietary protein with intraperitoneal amino acids (around 30% of daily requirement), without the delivered phosphate load attendant with oral complex protein may also be potentially significant.46.Tjiong H.L. van den Berg J.W. Wattimena J.L. et al.Dialysate as food: combined amino acid and glucose dialysate improves protein anabolism in renal failure patients on automated peritoneal dialysis.J Am Soc Nephrol. 2005; 16: 1486-1493Crossref PubMed Scopus (85) Google Scholar The systemic effects of absorbed GDPs are largely unknown. They appear to have some ability to modulate cardiovascular performance though. Our group has demonstrated significant differences in the cardiac output changes associated with PD exposure to 3.86% glucose dependant on the biocompatibility of the fluid presentation. No differences in venous bicarbonate were observed. GDP content was therefore the only significant differences between the two phases of study.33.Selby N.M. Fialova J. McIntyre C.W. The systemic haemodynamic and metabolic effects of peritoneal dialysis fluids.Nephrol Dial Transplant. 2006Google Scholar The clinical significance of these observations is still to be determined. Registry-based study does suggest survival benefit associated with the use of low GDP biocompatible glucose-based solutions.47.Lee H.Y. Park H.C. Seo B.J. et al.Superior patient survival for continuous ambulatory peritoneal dialysis patients treated with a peritoneal dialysis fluid with neutral pH and low glucose degradation product concentration (balance).Perit Dial Int. 2005; 25: 248-255PubMed Google Scholar There are a plethora of peritoneal and systemic structural, metabolic, and functional abnormalities that are related to the use of conventional fluids. Many of these adverse profiles can be addressed by the use of some or all of the expanding range of PD fluids. Potentially the optimal therapeutic approach may involve the combination of a variety of products, to gain the maximum potential benefits of high biocompatibility and maximum glucose substitution. The evidence is compelling that there are clear benefits for the patient. The major barrier to more widespread adoption of the current generation of PD fluids is related to increased acquisition costs. The difficult choices that health-care providers need to make are severely hampered by the lack of quality prospective outcome-based studies of these solutions directly compared to conventional glucose/lactate-based products. The design and execution of such appropriately powered hard outcome-based studies remains an urgent priority." @default.
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• W2016605436 title "Update on peritoneal dialysis solutions" @default.
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