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      Effect of peritoneal dialysis fluid containing osmo-metabolic agents on human endothelial cells

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          The use of glucose as the only osmotic agent in peritoneal dialysis (PD) solutions (PDSs) is believed to exert local (peritoneal) and systemic detrimental actions, particularly in diabetic PD patients. To improve peritoneal biocompatibility, we have developed more biocompatible PDSs containing xylitol and carnitine along with significantly less amounts of glucose and have tested them in cultured Human Vein Endothelial Cells (HUVECs) obtained from the umbilical cords of healthy (C) and gestational diabetic (GD) mothers.


          Primary C- and GD-HUVECs were treated for 72 hours with our PDSs (xylitol 0.7% and 1.5%, whereas carnitine and glucose were fixed at 0.02% and 0.5%, respectively) and two glucose-based PDSs (glucose 1.36% or 2.27%). We examined their effects on endothelial cell proliferation (cell count), viability (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay), intracellular nitro-oxidative stress (peroxynitrite levels), Vascular Cell Adhesion Molecule-1 and Intercellular Adhesion Molecule-1 membrane exposure (flow cytometry), and HUVEC-monocyte interactions (U937 adhesion assay).


          Compared to glucose-based PDSs, our in vitro studies demonstrated that the tested PDSs did not change the proliferative potential both in C- and GD-HUVECs. Moreover, our PDSs significantly improved endothelial cell viability, compared to glucose-based PDSs and basal condition. Notably, glucose-based PDSs significantly increased the intracellular peroxynitrite levels, Vascular Cell Adhesion Molecule-1 and Intercellular Adhesion Molecule-1 membrane exposure, and endothelial cell–monocyte interactions in both C- and GD-HUVECs, as compared with our experimental PDSs.


          Present results show that in control and diabetic human endothelial cell models, xylitol–carnitine-based PDSs do not cause cytotoxicity, nitro-oxidative stress, and inflammation as caused by hypertonic glucose-based PDSs. Since xylitol and carnitine are also known to favorably affect glucose homeostasis, these findings suggest that our PDSs may represent a desirable hypertonic solution even for diabetic patients in PD.

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          Most cited references 44

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          Relative contribution of residual renal function and peritoneal clearance to adequacy of dialysis: a reanalysis of the CANUSA study.

          Studies of the adequacy of peritoneal dialysis and recommendations have assumed that renal and peritoneal clearances are comparable and therefore additive. The CANUSA data were reanalyzed in an effort to address this assumption. Among the 680 patients in the original CANUSA study, 601 had all of the variables of interest for this report. Adequacy of dialysis was estimated from GFR (mean of renal urea and creatinine clearance) and from peritoneal creatinine clearance. The Cox proportional-hazards model was used to evaluate the time-dependent association of these independent variables with patient survival. For each 5 L/wk per 1.73 m(2) increment in GFR, there was a 12% decrease in the relative risk (RR) of death (RR, 0.88; 95% confidence interval [CI], 0.83 to 0.94) but no association with peritoneal creatinine clearance (RR, 1.00; 95% CI, 0.90 to 1.10). Estimates of fluid removal (24-h urine volume, net peritoneal ultrafiltration, and total fluid removal) then were added to the Cox model. For a 250-ml increment in urine volume, there was a 36% decrease in the RR of death (RR, 0.64; 95% CI, 0.51 to 0.80). The association of patient survival with GFR disappeared (RR, 0.99; 95% CI, 0.94 to 1.04). However, neither net peritoneal ultrafiltration nor total fluid removal was associated with patient survival. Although these results may be explained partly, statistically, by less variability in peritoneal clearance than in GFR, the latter seems to be physiologically more important than the former. The assumption of equivalence of peritoneal and renal clearances is not supported by these data. Recommendations for adequate peritoneal dialysis need to be reevaluated in light of these observations.
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            Predictors of loss of residual renal function among new dialysis patients.

            Residual renal function (RRF) in end-stage renal disease is clinically important as it contributes to adequacy of dialysis, quality of life, and mortality. This study was conducted to determine the predictors of RRF loss in a national random sample of patients initiating hemodialysis and peritoneal dialysis. The study controlled for baseline variables and included major predictors. The end point was loss of RRF, defined as a urine volume <200 ml/24 h at approximately 1 yr of follow-up. The adjusted odds ratios (AOR) and P values associated with each of the demographic, clinical, laboratory, and treatment parameters were estimated using an "adjusted" univariate analysis. Significant variables (P < 0.05) were included in a multivariate logistic regression model. Predictors of RRF loss were female gender (AOR = 1.45; P < 0.001), non-white race (AOR = 1.57; P = <0.001), prior history of diabetes (AOR = 1.82; P = 0.006), prior history of congestive heart failure (AOR = 1.32; P = 0.03), and time to follow-up (AOR = 1.06 per month; P = 0.03). Patients treated with peritoneal dialysis had a 65% lower risk of RRF loss than those on hemodialysis (AOR = 0.35; P < 0.001). Higher serum calcium (AOR = 0.81 per mg/dl; P = 0.05), use of an angiotensin-converting enzyme inhibitor (AOR = 0.68; P < 0.001). and use of a calcium channel blocker (AOR = 0.77; P = 0.01) were independently associated with decreased risk of RRF loss. The observations of demographic groups at risk and potentially modifiable factors and therapies have generated testable hypotheses regarding therapies that may preserve RRF among end-stage renal disease patients.
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              (7) Approaches to glycemic treatment.


                Author and article information

                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                28 November 2016
                : 10
                : 3925-3932
                [1 ]Unit of Nephrology and Dialysis
                [2 ]Department of Medicine and Aging Sciences
                [3 ]Department of Medical, Oral and Biotechnological Sciences
                [4 ]Aging Research Center and Translational Medicine, CeSI-MeT, University “G. d’Annunzio”, Chieti-Pescara
                [5 ]Department DiBEST (Biologia, Ecologia, Scienze della Terra), Unit of Biochemistry and Molecular Biotechnology, University of Calabria, Arcavacata di Rende CS, Italy
                [6 ]CoreQuest, Manno, Switzerland
                Author notes
                Correspondence: Mario Bonomini, Unit of Nephrology and Dialysis, SS. Annunziata Hospital, Via dei Vestini, 66013 Chieti, Italy, Tel +39 0871 540 120, Fax +39 0871 574 736, Email m.bonomini@ 123456nephro.unich.it
                © 2016 Bonomini et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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