Hypertonic Peritoneal Dialysis Solution Research Articles

Association of Prescription With Body Composition and Patient Outcomes in Incident Peritoneal Dialysis Patients.

Objective: The nutritional status of patients on peritoneal dialysis (PD) is influenced by patient- and disease-related factors and lifestyle. This analysis evaluated the association of PD prescription with body composition and patient outcomes in the prospective incident Initiative for Patient Outcomes in Dialysis–Peritoneal Dialysis (IPOD-PD) patient cohort.Design and Methods: In this observational, international cohort study with longitudinal follow-up of 1,054 incident PD patients, the association of PD prescription with body composition was analyzed by using the linear mixed models, and the association of body composition with death and change to hemodialysis (HD) by means of a competing risk analysis combined with a spline analysis. Body composition was regularly assessed with the body composition monitor, a device applying bioimpedance spectroscopy.Results: Age, time on PD, and the use of hypertonic and polyglucose solutions were significantly associated with a decrease in lean tissue index (LTI) and an increase in fat tissue index (FTI) over time. Competing risk analysis revealed a U-shaped association of body mass index (BMI) with the subdistributional hazard ratio (HR) for risk of death. High LTI was associated with a lower subdistributional HR, whereas low LTI was associated with an increased subdistributional HR when compared with the median LTI as a reference. High FTI was associated with a higher subdistributional HR when compared with the median as a reference. Subdistributional HR for risk of change to HD was not associated with any of the body composition parameters. The use of polyglucose or hypertonic PD solutions was predictive of an increased probability of change to HD, and the use of biocompatible solutions was predictive of a decreased probability of change to HD.Conclusion: Body composition is associated with non-modifiable patient-specific and modifiable treatment-related factors. The association between lean tissue and fat tissue mass and death and change to HD in patients on PD suggests developing interventions and patient counseling to improve nutritional markers and, ultimately, patient outcomes.Study Registration: The study has been registered at Clinicaltrials.gov (NCT01285726).

Comparison of mesenchymal stromal cells from peritoneal dialysis effluent with those from umbilical cords: characteristics and therapeutic effects on chronic peritoneal dialysis in uremic rats

BackgroundA long-term of peritoneal dialysis (PD) using a hypertonic PD solution (PDS) leads to patient’s peritoneal membrane (PM) injury, resulting in ultrafiltration failure (UFF) and PD drop-out. Our previous study shows that PD effluent-derived mesenchymal stromal cells (pMSCs) prevent the PM injury in normal rats after repeated exposure of the peritoneal cavity to a PDS. This study was designed to compare the cytoprotection between pMSCs and umbilical cord-derived MSCs (UC-MSCs) in the treatment of both PM and kidney injury in uremic rats with chronic PD.Methods5/6 nephrectomized (5/6Nx) Sprague Dawley rats were intraperitoneally (IP) injected Dianeal (4.25% dextrose, 10 mL/rat/day) and were treated with pMSCs or umbilical cord (UC)-MSCs (approximately 2 × 106/rat/week, IP). Ultrafiltration was determined by IP injection of 30 mL of Dianeal (4.25% dextrose) with 1.5-h dewell time, and kidney failure by serum creatinine (SCr) and blood urea nitrogen (BUN). The structure of the PM and kidneys was assessed using histology. Gene expression was examined using quantitative reverse transcription PCR, and protein levels using flow cytometric and Western blot analyses.ResultsWe showed a slight difference in the morphology between pMSCs and UC-MSCs in plastic dishes, and significantly higher expression levels of stemness-related genes (NANOG, OCT4, SOX2, CCNA2, RAD21, and EXO1) and MSCs surface markers (CD29, CD44, CD90 and CD105) in UC-MSCs than those in pMSCs, but no difference in the differentiation to chondrocytes, osteocytes or adipocytes. pMSC treatment was more effective than UC-MSCs in the protection of the MP and remnant kidneys in 5/6Nx rats from PDS-induced injury, which was associated with higher resistance of pMSCs than UC-MSCs to uremic toxins in culture, and more reduction of peritoneal mesothelial cell death by the secretome from pMSCs than from UC-MSCs in response to PDS exposure. The secretome from both pMSCs and UC-MSCs similarly inactivated NOS2 in activated THP1 cells.ConclusionsAs compared to UC-MSCs, pMSCs may more potently prevent PDS-induced PM and remnant kidney injury in this uremic rat model of chronic PD, suggesting that autotransplantation of ex vivo-expanded pMSCs may become a promising therapy for UFF and deterioration of remnant kidney function in PD patients.

Protection of the Peritoneal Membrane by Peritoneal Dialysis Effluent-Derived Mesenchymal Stromal Cells in a Rat Model of Chronic Peritoneal Dialysis.

Peritoneal dialysis (PD) is a renal replacement option for patients with end-stage renal disease. However, a long-term exposure to hypertonic PD solutions leads to peritoneal membrane (PM) injury, resulting in ultrafiltration (UF) failure. This study was designed to primarily evaluate efficacy of PD effluent-derived mesenchymal stromal cells (pMSCs) in the prevention of PM injury in rats. The pMSCs were isolated from PD effluent. Male Wistar rats received daily intraperitoneal (IP) injection of 10 mL of Dianeal (4.25% dextrose) and were treated with pMSCs (1.2‐1.5 × 106/rat/wk, IP). UF was determined by IP injection of 30 mL of Dianeal (4.25% dextrose) with dwell time of 1.5 h, and PM injury was examined by histology. Apoptosis was quantitated by using flow cytometric analysis, and gene expression by using the PCR array and Western blot. Here, we showed that as compared to naive control, daily IP injection of the Dianeal PD solution for 6 weeks without pMSC treatment significantly reduced UF, which was associated with an increase in both PM thickness and blood vessel, while pMSC treatment prevented the UF loss and reduced PM injury and blood vessels. In vitro incubation with pMSC-conditioned medium prevented cell death in cultured human peritoneal mesothelial cells (HPMCs) and downregulated proinflammatory (i.e., CXCL6, NOS2, IL1RN, CCL5, and NR3C1) while upregulated anti-inflammatory (i.e., CCR1, CCR4, IL9, and IL-10) gene expression in activated THP1 cells. In conclusion, pMSCs prevent bioincompatible PD solution-induced PM injury and UF decline, suggesting that infusing back ex vivo-expanded pMSCs intraperitoneally may have therapeutic potential for reduction of UF failure in PD patients.

Comparison of sirolimus and colchicine treatment on the development of peritoneal fibrozis in rats having peritoneal dialysis.

Continuous ambulatory peritoneal dialysis is a successful treatment modality for patients with end-stage renal disease. Peritoneal fibrosis (PF) is the most critical complication of long-term peritoneal dialysis (PD). In our study, we aimed to compare the effects of colchicine and sirolimus on PF induced by hypertonic peritoneal dialysis solutions in rats. Animal experiment. Twenty-four rats were randomly divided into three groups. The control group received an intraperitoneal injection (ip) of saline. The sirolimus group received the PD solution, plus 1.0 mg/kg/day Rapamune®. The colchicine group received the PD solution ip plus 1.0 mg/kg/day of colchicine. Blood samples were taken to measure the serum levels of VEGF, TGF-β, and TNF-α. Peritoneal tissue samples were taken for histopathological evaluation. TGF-β and TNF-α values in the sirolimus group were found to be statistically significantly lower than in the control and colchicine groups, but the differences between the control and colchicine groups were not statistically significant. No statistically significant differences were found between the groups regarding the VEGF values. Vascular neogenesis and peritoneal thickness were compared; the values in the sirolimus group were statistically reduced compared to the values in the control group. Mild fibrosis developed in 75% of all animals in the sirolimus group; there was no moderate or severe fibrosis observed. Fibrosis developed to varying degrees in 100% of the animals in the control and colchicine groups. The present study demonstrates that sirolimus might be beneficial for preventing or delaying the progression of PF and neoangiogenesis. These alterations in the peritoneal membrane may be connected with reduced TNF-α and TGF-β levels.

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Introduction: Adjunctive direct peritoneal resuscitation (DPR) with hypertonic peritoneal dialysis solution in addition to conventional resuscitation from hemorrhagic shock (HS) mitigates visceral organ injury via improved visceral blood flow (VBF) but the effect on remote organs has not been evaluated. Hypothesis: We hypothesized that DPR would decrease acute lung injury (ALI) after hemorrhagic shock. Methods: Anesthetized rats were bled to 40% MAP for 60 min to induce HS and were randomly assigned to resuscitation with shed blood + NS (CR, n=8), or CR + 30 ml of IP 2.5% Delflex (DPR, n=8). Protein expression was measured using multiplex array and individual ELISA, mRNA expression via PcR and organ injury graded in blinded manner. One way ANOVA with Tukey-Kramer was performed at a significance at p<0.01. Results: Enhanced VBF was seen in the DPR group (not shown). Lung sections from DPR animals had less edema and enhanced structural integrity. Wet to dry weight ratios for the DPR group were decreased compared to CR. (Sham 4.92 ± 0.08; CR 5.37+0.12; DPR 4.91 ± 0.07, p<0.01) Cytosolic migration of HMGB-1 (a nuclear regulatory protein) confirmed the breakdown of nuclear/cellular integrity in CR animals. Nuclear sequestration of HMGB-1 was preserved in the DPR and sham. Serum HMGB-1 levels were increased in CR compared to DPR indicating cellular necrosis with cytosolic release. (1.2 ± 0.2 vs. 6.88 ± 0.9 ng/ml, DPR vs. CR, p<0.01) Th1 serum cytokine levels were reduced in DPR animals when compared to CR. (IL1a: 10.7 ± 0.7 vs. 26.7 ± 2.7 mg/ml; INFg: 1148+23 vs. 1213 ± 88 ng/ml, DPR vs. CR; p<0.01) CR increased lung IL18 and IL12p70 protein (IL18: 5255 ± 535 vs. 6948 ± 545 ng/g; IL12p70: 19.6 ± 0.5 vs. 21.3 ± 0.7 ng/g; DPR vs. CR p<0.01) and increased mRNA expression of IL18 (+1.2 DPR/sham vs. +3.8 CR/sham, P<0.01) indicating activation and expression of these proteins in lung tissue. This correlated with increase serum level in CR compared to DPR. (IL18: 117 ± 17 vs. 213 ± 15 ng/ml; IL-12p70: 14.4 ± 0.9 vs. 13.1 ± 0.5; DPR vs. CR, p<0.01) Conclusions: DPR reduces pulmonary edema and maintains lung cellular and nuclear architecture after HS. DPR decreases shock-induced ALI possibly due to attenuating the Th1 inflammatory response.

The Effect of Weather on Peritoneal Dialysis (PD) Prescription: Seasonal Variation in PD Dialysate Utilization

There have been no reports on peritoneal dialysis (PD) solution utilization since this treatment was developed in the 1920s. The aim of the present investigation was to investigate if weather affects PD prescription. This 10-year observational study used the Taiwan National Health Insurance Research Database. Claims for different concentrate PD dialysate were analyzed monthly. 2.5% and 4.25% PD solutes were defined as hypertonic solutions. Monthly outdoor mean temperature. Outcome and Measurement: The relationship between monthly mean of PD dialysate utilization and monthly outdoor temperature was analyzed by linear regression. Monthly mean PD dialysate utilization amount in 4 quarters was analyzed by ANOVA. During the 10-year study period, a clear seasonal variation in PD dialysate was observed. This seasonal variation was present regardless of age, gender, and the presence of hypertension, diabetes, and dyslipidemia. Monthly mean temperature was positively correlated to 1.5% dialysate utilization amount (r = 0.559, p < 0.001) and negatively correlated to 2.5% (r = -0.533, p < 0.001) and 4.25% (r = -0.410, p < 0.001) dialysate utilization amount. In longitudinal follow-up, hypertonic PD fluid utilization was higher in diabetic patients than in nondiabetic patients from the beginning of treatment. Thereafter, it increased rapidly and reached a plateau within 1 year. Analysis of ultrafiltration amount, blood pressure, and body weight was unfeasible due to the nature of the database. The utilization of differential strengths of PD solutions has a seasonal cyclic pattern, with more hypertonic PD solution utilized in winter and more hypotonic PD solution in summer.

Volume Control Associated with Better Cardiac Function in Long-Term Peritoneal Dialysis Patients

This study was undertaken to investigate the effect of long-term blood pressure (BP) reduction, achieved with salt restriction and strict volume control, on frequency and regression of left ventricular hypertrophy (LVH) in long-term peritoneal dialysis (PD) patients. 56 patients who had been treated for more than 2 years under our care were enrolled. After echocardiographic (Echo) evaluation, 46 patients were included in the follow-up study. In our unit, we aim to keep patients' BP below 130/85 mmHg and cardiothoracic index below 0.50. To reach these targets, moderate salt restriction is advised, and if necessary, hypertonic PD solutions are used. Echo was performed at the beginning of the study (after a mean period of 36 months on PD) and at the end of the prospective follow-up period (24 months later). At the time of the first Echo, LVH was detected in only 8 (21%) patients. Residual urine volume was significantly decreased compared to data taken when they first started PD (658 +/- 795 vs 236 +/- 307 mL/day). Mean left ventricular mass index (LVMI) was 107 +/- 26.5 g/m2. LVMI was significantly decreased at the end of the follow-up in patients who had LVH at baseline. No LVH developed in patients who had normal LVMI at baseline. Our results indicate that control of hypertension is possible when extracellular fluid volume is kept under control using hypertonic PD solutions in case of recruitment in addition to salt restriction in long-term PD patients. Sustained normovolemia is associated with low incidence and regression of LVH.

The Effect of Colchicine on the Peritoneal Membrane

Peritoneal dialysis (PD) is a treatment modality for patients with renal failure. Peritoneal fibrosis is one of the most serious complications after long-term continuous ambulatory peritoneal dialysis (CAPD). Histological studies in both humans and animals show that chronic peritoneal dialysis results in fibrosis of the peritoneal membrane. In our study, we investigated the effect of colchicine on peritoneal alterations induced by hypertonic PD solution in rats. Sprague-Dawley rats intraperitoneally received saline (control group) once daily, for 28 days, or 3.86% glucose (PDF group), or 3.86% glucose plus colchicine (colchicine group). Animals from each group were sacrificed after 28 days with anesthetized ketamine (60 mg/kg BW). For the PD fluid assessment, 1 h before the sacrifice of animals, 10 mL PD fluid of 2.27% glucose was given, and this fluid was obtained after the sacrifice. The levels of transforming endothelial growth factor β (TGF-β), tumor necrosis factor α (TNF-α) and albumin were investigated both in the peritoneal dialysate and blood, and the levels of malondialdehyde (MDA) were investigated only in peritoneal dialysate. The peritoneal membrane was evaluated histologically by light microscopy. When groups were compared in terms of body weight change, the colchicine group significantly lost weight compared to controls and PDF group (−4.7% ± 4.5, 3.5% ± 7.2, 3.0% ± 1.3, respectively, p = 0.018). Also, the blood albumin level was significantly lower for these in the colchicine group compared to those in the PDF group (2.7 ± 0.35 versus 3.2 ± 0.3 g/dL, respectively, p = 0.048). The blood TGF-β level was significantly lower in the control group, and no difference was observed between the PDF and colchicine groups (294.4 ± 67.5 versus 787.4 ± 237.4 versus 615.3 ± 235.1 pg/mL, respectively, p = 0.004). The mesothelial thickness found in groups was as follows: control group 102 ± 18.9 µm, PDF group 128.33 ± 33.1 µm, colchicine group 117 ± 35.6 µm (p = 0.34). In conclusion, a rat model for peritoneal dialysis associated peritoneal derangement without fibrosis could be induced. Colchicine could not prevent peritoneal derangement in this model.

By Reducing Production of Vascular Endothelial Growth Factor Octreotide Improves the Peritoneal Vascular Alterations Induced by Hypertonic Peritoneal Dialysis Solution

Chronic peritoneal dialysis (PD) may eventually result in vascular alterations of varying degree, which lead to progressive reduction in dialytic efficacy. Although the pathogenesis has not been elucidated yet, vascular endothelial growth factor (VEGF) has been proposed to play a central role in the process leading to vascular alterations. Rats were allocated to three groups: no treatment, intraperitoneal introduction of hypertonic PD solution alone, and intraperitoneal introduction of hypertonic PD solution plus octreotide. After 4 weeks, a 1-hour peritoneal equilibration test (PET) was performed. Dialysate-to-plasma urea ratio (D/P urea), glucose reabsorption (D1/D0 glucose), ultrafiltration volume (UF), and levels of dialysate protein and VEGF were determined. Peritoneal membrane histology was evaluated by light microscopy. Compared with the control group, rats treated with hypertonic PD solution showed dramatically deranged peritoneal function tests (UF: 5.8 +/- 0.9 mL vs 1.3 +/- 0.6 mL; D/P urea: 0.49 +/- 0.1 vs 0.74 +/- 0.04; D1/D0 glucose: 0.55 +/- 0.05 vs 0.34 +/- 0.06) and morphology (thickness: 4.6 +/- 0.4 mu vs 62 +/- 12 mu; neovascularisation: 0.1 +/- 0.3 vessels per field vs 2.2 +/- 0.3 vessels per field). Similarly, a higher level of VEGF was found in the rats treated with hypertonic PD solution. In rats treated with hypertonic solution plus octreotide, peritoneal thickness was not completely reduced (25 +/- 5 mu), but peritoneal functions were protected (UF: 4.0 +/- 0.5 mL; D/P urea: 0.58 +/- 0.02; D1/D0 glucose: 0.51 +/- 0.02). Moreover, VEGF level and neoangiogenesis were significantly less in the octreotide group than in the group treated with hypertonic dextrose alone. Our data document that, by increasing the production of VEGF, a high glucose concentration can cause vascular alterations within the peritoneal membrane. Octreotide can protect against the vascular alterations and preserve peritoneal function by inhibiting overexpression of VEGF and regulating the inflammatory response in the peritoneum.

Effects of Hypertonic Peritoneal Dialysis Solutions on Neutrophil Superoxide Production

Superoxide produced by neutrophils plays an important role in the killing of bacterial pathogens. The effects of glucose-containing peritoneal dialysis solutions on superoxide production by canine and human neutrophils were studied. A significant decrement in superoxide generation was noted with the 2.27% and 3.86% glucose solutions. The results suggest that hypertonic peritoneal dialysis solutions curtail neutrophil superoxide generation.