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Background: Controversy surrounds which factors are important for predicting early mortality after dialysis initiation (DI). We investigated associations of predialysis course and circumstances affecting planning and execution of DI with mortality following DI. Methods: Among 1580 patients participating in the Peridialysis study, a study of causes and timing of DI, we registered features of predialysis course, clinical and biochemical data at DI, incidence of unplanned suboptimal DI, contraindications to peritoneal dialysis (PD) or hemodialysis (HD), and modality preference, actual choice, and cause of modality choice. Patients were followed for 12 months or until transplantation. A flexible parametric model was used to identify independent factors associated with all-cause mortality. Results: First-year mortality was 19.33%. Independent factors predicting death were high age, comorbidity, clinical contraindications to PD or HD, suboptimal DI, high eGFR, low serum albumin, hyperphosphatemia, high C-reactive protein, signs of overhydration and cerebral symptoms at DI. Among 1061 (67.2%) patients who could select dialysis modality based on personal choice, 654 (61.6%) chose PD, 368 (34.7%) center HD and 39 (3.7%) home HD. The 12-months survival did not differ significantly between patients receiving PD and in-center HD. Conclusions: First-year mortality in incident dialysis patients was in addition to high age and comorbidity, associated with clinical contraindications to PD or HD, clinical symptoms, hyperphosphatemia, inflammation, and suboptimal DI. In patients with a “free” choice of dialysis modality based on their personal preferences, PD and in-center HD led to broadly similar short-term outcomes.

BackgroundPeripheral arterial disease and vascular calcifications contribute significantly to the outcome of dialysis patients. The aim of this study was to evaluate the prognostic role of severity of abdominal aortic calcifications and peripheral arterial disease on outcome of peritoneal dialysis (PD) patients using methods easily available in everyday clinical practice.MethodsWe enrolled 249 PD patients (mean age 61 years, 67% male) in this prospective, observational, multicenter study from 2009 to 2013. The abdominal aortic calcification score (AACS) was assessed using lateral lumbar X ray, and the ankle-brachial index (ABI) using a Doppler device.ResultsThe median AACS was 11 (range 0 – 24). In 58% of the patients, all 4 segments of the abdominal aorta showed deposits, while 19% of patients had no visible deposits (AACS 0). Ankle-brachial index was normal in 49%, low (< 0.9) in 17%, and high (> 1.3) in 34% of patients. Altogether 91 patients (37%) died during the median follow-up of 46 months. Only 2 patients (5%) with AACS 0 died compared with 50% of the patients with AACS ≥ 7 ( p < 0.001). The adjusted hazard ratio for all-cause mortality was 4.85 (95% confidence interval [CI] 1.94 – 24.46) for aortic calcification (AACS ≥ 7), 2.14 for diabetes (yes/no), 0.93 for albumin (per 1 g/L), and 1.04 for age (per year). A low or high ABI were not independently associated with mortality.ConclusionsSevere aortic calcification was a strong predictor of all-cause mortality in PD patients. The evaluation of aortic calcifications by lateral X ray is a simple method that allows the identification of high-risk patients.

Background The mortality following blood stream infection (BSI) and risk of subsequent BSI in relation to dialysis modality, vascular access, and other potential risk factors has received relatively little attention. Consequently, we assessed these matters in a retrospective cohort study, by use of the Danish nation-wide registries. Methods Patients more than 17 years of age, who initiated dialysis between 1.1.2010 and 1.1.2014, were grouped according to their dialysis modality and vascular access. Survival was modeled in time-dependent Cox proportional hazard analyses. Potential risk factors confined by a modified Charlson comorbidity index (MCCI), were subsequently assessed in stepwise selection models. Results At baseline, 764 patients received peritoneal dialysis (PD), and 434, 479, and 782 hemodialysis (HD) patients were dialyzed by use of arteriovenous fistulas (AVFs), tunneled catheters (TCs), and non-tunneled catheters (NTCs), respectively. We identified 1069 BSIs with an overall incidence rate of 17.7 episodes per 100 person years, and 216 BSIs occurred more than one time in the same patient. HRs of post BSI mortality relative to PD were 3.20 (95% CI 1.86–5.50; p

Encapsulating peritoneal sclerosis (EPS) is a potentially devastating complication of peritoneal dialysis\ud (PD). Diagnosis is often delayed due to the lack of effective and accurate diagnostic tools. We\ud therefore examined peritoneal effluent for potential biomarkers that could predict or confirm the\ud diagnosis of EPS and would be valuable in stratifying at-risk patients, and driving appropriate\ud interventions. Using prospectively collected samples from the Global Fluid Study and a cohort of\ud Greek PD patients, we utilized 2D SDSPAGE/ MS and iTRAQ to identify changes in the peritoneal\ud effluent proteome from patients diagnosed with EPS and controls matched for treatment exposure. We\ud employed a combinatorial peptide ligand library to compress the dynamic range of protein\ud concentrations, to aid identification of low-abundance proteins. In patients with stable membrane\ud function, fibrinogen γ-chain and heparan sulphate proteoglycan core protein progressively\ud increased over time on PD. In patients who developed EPS, collagen-α1(I), γ-actin and Complement\ud factors B and I were elevated up to five years prior to diagnosis. Orosomucoid-1 and a2-HSglycoprotein chain-B were elevated about one year before diagnosis, while apolipoprotein A-IV and\ud α1-antitrypsin were decreased compared to controls. Dynamic range compression resulted in an\ud increased number of proteins detected with improved resolution of protein spots, compared to the full\ud fluid proteome. Intelectin-1, dermatopontin, gelsolin and retinol binding protein-4 were elevated in\ud proteome-mined samples from patients with EPS compared to patients that had just commenced\ud peritoneal dialysis. Thus, prospective analysis of peritoneal effluent uncovered proteins indicative of\ud inflammatory and pro-fibrotic injury worthy of further evaluation as diagnostic/prognostic markers.

Peritoneal dialysis (PD)-induced peritonitis leads to dysfunction of the peritoneal membrane. During peritonitis, neutrophils are recruited to the inflammation site by rolling along the endothelium, adhesion, and transmigration through vessel walls. In a rat PD-model, long-term effects of PD-fluids (PDF) on leukocyte-endothelium interactions and neutrophil migration were studied under baseline and inflammatory conditions. Rats received daily conventional-lactate-buffered PDF (Dianeal), bicarbonate/lactate-buffered PDF (Physioneal) or bicarbonate/lactate buffer (Buffer) during five weeks. Untreated rats served as control. Baseline leukocyte rolling and N-formylmethionyl-leucyl-phenylalanine (fMLP) induced levels of transmigration in the mesentery were evaluated and quantified by intra-vital videomicroscopy and immunohistochemistry. Baseline leukocyte rolling was unaffected by buffer treatment, approximately 2-fold increased after Physioneal and 4-7-fold after Dianeal treatment. After starting fMLP superfusion, transmigrated leukocytes appeared outside the venules firstly after Dianeal treatment (15 minutes), thereafter in Physioneal and Buffer groups (20-22 minutes), and finally in control rats (>25 minutes). Newly formed vessels and total number of transmigrated neutrophils were highest in Dianeal-treated animals, followed by Physioneal and Buffer, and lowest in control rats and correlated for all groups to baseline leukocyte rolling (r = 0.78, P < 0.003). This study indicates that the start of inflammatory neutrophil transmigration is related to PDF bio(in)compatibility, whereas over time neutrophil transmigration is determined by the degree of neo-angiogenesis.

Peritoneal dialysis (PD) is associated with functional and structural changes of the peritoneal membrane. In this review we describe factors contributing to peritoneal tissue remodeling, including uremia, peritonitis, volume loading, the presence of a catheter, and the PD fluid itself. These factors initiate recruitment and activation of peritoneal cells such as macrophages and mast cells, as well as activation of peritoneal cells, including mesothelial cells, fibroblasts, and endothelial cells. We provide an overview of cytokines, growth factors, and other mediators involved in PD-associated changes. Activation of downstream pathways of cellular modulators can induce peritoneal tissue remodeling, leading to ultrafiltration loss. Identification of molecular pathways, cells, and cytokines involved in the development of angiogenesis, fibrosis, and membrane failure may lead to innovative therapeutic strategies that can protect the peritoneal membrane from the consequences of long-term PD.

BACKGROUND: Peritoneal dialysis (PD) is associated with functional and structural alterations of the peritoneal membrane, particularly new vessel formation and fibrosis. In addition to anticoagulant effects, heparin displays anti-inflammatory and angiostatic properties. Therefore, the effects of administration of heparins on function and morphology of the peritoneal membrane were studied in a rat PD model.METHODS: Rats received 10 mL conventional PD fluid (PDF) daily, with or without the addition of unfractionated heparin (UFH) or low molecular weight heparin (LMWH) in the PDF (1 mg/10 mL intraperitoneally) via a mini access port. Untreated rats served as controls. After 5 weeks, a 90-minute functional peritoneal transport test was performed and tissues and peritoneal leukocytes were taken.RESULTS: PD treatment induced loss of ultrafiltration (pCONCLUSION: Within 5 weeks, PD treatment induces a chronic inflammatory condition in the peritoneum, evidenced by high transport, leukocyte recruitment, tissue remodeling, and induction of spindle-shaped cells in the mesothelium. Addition of LMWH or UFH to the PDF did not prevent these adverse PDF-induced peritoneal changes.

BACKGROUND: In experimental peritoneal dialysis (PD) studies, the occurrence of peritonitis is a confounder in the interpretation of effects of chronic peritoneal exposure to dialysis solutions. Since fluid cannot be drained in most experimental PD models in the rat, it is impossible to diagnose peritonitis based on dialysate white blood cell counts. To study the value of serum markers for the presence of peritonitis, alpha-2-macroglobulin (alpha2M) and albumin were measured in rats with and without peritonitis after chronic exposure to dialysis solutions. To further investigate the time course of these markers in relation to the severity of peritonitis, nondialyzed rats were challenged with increasing numbers of bacteria and followed for 28 days.METHODS: In the first study, alpha2M and albumin were measured in rats exposed to glucose/lactate-based dialysis fluid before sacrifice. A comparison was made between animals with peritonitis, as judged from the presence of extensive infiltrates after sacrifice (gold standard) and/or clinical signs of peritonitis, or absence of peritonitis and infiltrates. In the second study, rats were intraperitoneally (IP) injected with 3 different concentrations of Staphylococcus aureus, and serum alpha2M and albumin were measured at various time points.RESULTS: In the first study, serum alpha2M was higher and serum albumin was lower in animals with peritonitis compared to animals without peritonitis (both p < 0.05). In the second study, induction of alpha2M was clearly dependent on the inoculum concentration. Peak values of alpha2M were found at days 1 and 3. At all time points after inoculation, alpha2M was higher in all injected groups compared to the control group. Serum albumin values decreased in the highest inoculum group and remained decreased until 28 days after IP injection. Despite a low sensitivity, serum alpha2M > 40 mg/L and albumin < 32 g/L had a specificity of 100% for peritonitis.CONCLUSIONS: Measurement of alpha2M and albumin once per month is an additional tool in the diagnosis of silent peritonitis in the chronic peritoneal exposure model in the rat. Levels of alpha2M > 40 mg/L and albumin < 32 g/L are strong indicators for peritonitis. However, normal values do not exclude infectious peritonitis.

BACKGROUND: Chronic exposure to conventional peritoneal dialysis fluid (PDF) is associated with functional and structural alterations of the peritoneal membrane. The bioincompatibility of conventional PDF can be due to hypertonicity, high glucose concentration, lactate buffering system, presence of glucose degradation products (GDPs) and/or acidic pH. Although various investigators have studied the sole effects of hyperosmolarity, high glucose, GDPs and lactate buffer in experimental PD, less attention has been paid to the chronic impact of low pH in vivo.METHODS: Rats received daily 10 ml of either conventional lactate-buffered PDF (pH 5.2; n=7), a standard bicarbonate/lactate-buffered PDF with physiological pH (n=8), bicarbonate/lactate-buffered PDF with acidic pH (adjusted to pH 5.2 with 1 N hydrochloride, n=5), or bicarbonate/lactate buffer, without glucose, pH 7.4 (n=7). Fluids were instilled via peritoneal catheters connected to implanted subcutaneous mini vascular access ports for 8 weeks. Control animals with or without peritoneal catheters served as control groups (n=8/group). Various functional (2 h PET) and morphological/cellular parameters were analyzed.RESULTS: Compared with control groups and the buffer group, conventional lactate-buffered PDF induced a number of morphological/cellular changes, including angiogenesis and fibrosis in various peritoneal tissues (all parameters PCONCLUSION: The bicarbonate/lactate-buffered PDF, acidity per se did not contribute substantially to peritoneal worsening in our in vivo model for PD, which might be explained by the buffering capacity of the peritoneum.

BACKGROUND: Peritoneal dialysis (PD) is associated with functional and structural alterations of the peritoneal membrane. However, the (ir)reversibility of these pathological changes of the peritoneum is not understood fully.METHODS: In an experimental PD model, rats (n = 15) received daily 10 ml conventional glucose containing PD fluid, via peritoneal catheters connected to implanted subcutaneous mini vascular access ports. After 5 weeks of treatment, the first group of animals (PDF; n = 10) was sacrificed, while peritoneal catheters of the remaining group of rats (PD-rest; n = 5) were removed 1 week later. The latter group (PD-rest) was sacrificed 12 weeks after removing catheters. At both time points, untreated rats were included as controls. Cellular and morphological parameters were analysed by light and electron microscopy.RESULTS: Rats exposed to PD fluid for 5 weeks showed a severe angiogenesis in various peritoneal tissues. Peritoneal rest resulted in a significant reduction in blood vessel density in visceral (mesentery, PCONCLUSIONS: We show that PD fluid-induced cellular and morphological alterations of the peritoneal membrane are generally reversible.

OBJECTIVES: Mesothelial cell (MC) injury caused by continuous exposure to unphysiological peritoneal dialysis (PD) fluid and by episodes of peritonitis can eventually lead to peritoneal adhesions and peritoneal fibrosis. In the present study, we evaluated the possibility of using autologous genetically modified MCs for transplantation after the induction of peritoneal injury by acute inflammatory mediators or chronic instillation of PD fluid. METHODS: Rats were injected intraperitoneally either once with N-formyl-methionyl-leucyl-phenylalanine (fMLP), or thioglycollate, or PD fluid [i.e., Dianeal (Baxter Healthcare, Deerfield, Illinois, USA) or Physioneal (Baxter, Nivelles, Belgium)], or chronically (up to 8 weeks) with Dianeal. From 2 to 48 hours later, animals were injected with syngeneic MCs genetically modified to express the LacZ reporter gene. Rats were sacrificed 2 days later and expression of beta-galactosidase (beta-Gal) was visualized by X-Gal staining of excised tissues. Quantification of the percent area of beta-Gal-positive MCs on part of the parietal peritoneum was performed using computerized image analysis. RESULTS: The highest numbers of repopulated genetically modified MCs were observed 8 hours after a single thioglycollate injection, approximately 0.66% of a representative 2-cm2 area selected for study (corresponding to approximately 10% of the peritoneal surface). The number of genetically modified MCs found to repopulate the peritoneal surface following short-term injury varied with inflammatory mediator (thioglycollate > PD fluid > fMLP) and duration of exposure. No obvious differences were observed between the two PD fluids tested. Reimplantation of syngeneic genetically modified MCs was also observed after chronic instillation of PD fluid. CONCLUSIONS: These data demonstrate that transplanted genetically modified MCs repopulate the denuded areas on the peritoneal surface that were caused by acute or chronic inflammation. This technique opens possibilities of MC transplantation and gene therapy in order to prevent complications relevant to the continuous ambulatory PD setting.

Introduction: The aim of the study was to identify biomarkers of alteration in bone mineral density (BMD) in patients on haemodialysis (HD) and peritoneal dialysis (PD). Materials and methods: In a cross-sectional, longitudinal study dual-energy X-ray absorptiometry scans were performed in 146 HD-patients and 28 PD-patients. Follow-up after 14 months (mean) was conducted in 73 patients. As potential biomarkers we investigated parathyroid hormone (PTH), 25-hydroxy vitamin-D, ionised calcium, albumin, phosphate, and total alkaline phosphatases (t-ALP). Results: Both groups of dialysis patients had lower BMD in the femoral neck (BMD neck) (P < 0.001) and forearm (BMD forearm) (P < 0.001) compared to healthy controls, but comparable BMD in the lumbar spine (BMD spine). BMD did not differ between dialysis types, but patients ever-treated with glucocorticoids had significantly lower BMD, while patients with polycystic kidney disease had higher BMD. BMD correlated with body weight, actual age, age at initiation of dialysis, duration of dialysis and levels of PTH and t-ALP. However, t-ALP only remained associated with low BMD spine after adjusting for other factors (P = 0.001). In the follow-up study all patients had decreased BMD in all three locations, but only for the lumbar spine there was a significant association between BMD and the bone markers t-ALP (P = 0.009) and PTH (P = 0.013). Conclusions: Both HD and PD patients have low BMD, and increased concentrations of t-ALP is associated BMD spine after adjustment, while PTH and t-ALP is associated with decrease in BMD spine over time. This substantiates the use of these biomarkers in both types of dialysis patients.

Peritoneal dialysis (PD)-induced peritonitis leads to dysfunction of the peritoneal membrane. During peritonitis, neutrophils are recruited to the inflammation site by rolling along the endothelium, adhesion, and transmigration through vessel walls. In a rat PD-model, long-term effects of PD-fluids (PDF) on leukocyte-endothelium interactions and neutrophil migration were studied under baseline and inflammatory conditions. Rats received daily conventional-lactate-buffered PDF (Dianeal), bicarbonate/lactate-buffered PDF (Physioneal) or bicarbonate/lactate buffer (Buffer) during five weeks. Untreated rats served as control. Baseline leukocyte rolling and N-formylmethionyl-leucyl-phenylalanine (fMLP) induced levels of transmigration in the mesentery were evaluated and quantified by intra-vital videomicroscopy and immunohistochemistry. Baseline leukocyte rolling was unaffected by buffer treatment, approximately 2-fold increased after Physioneal and 4-7-fold after Dianeal treatment. After starting fMLP superfusion, transmigrated leukocytes appeared outside the venules firstly after Dianeal treatment (15 minutes), thereafter in Physioneal and Buffer groups (20-22 minutes), and finally in control rats (>25 minutes). Newly formed vessels and total number of transmigrated neutrophils were highest in Dianeal-treated animals, followed by Physioneal and Buffer, and lowest in control rats and correlated for all groups to baseline leukocyte rolling (r = 0.78, P < 0.003). This study indicates that the start of inflammatory neutrophil transmigration is related to PDF bio(in)compatibility, whereas over time neutrophil transmigration is determined by the degree of neo-angiogenesis.

Background Peritoneal dialysis (PD) is associated with functional and structural alterations of the peritoneal membrane, particularly new vessel formation and fibrosis. In addition to anticoagulant effects, heparin displays anti-inflammatory and angiostatic properties. Therefore, the effects of administration of heparins on function and morphology of the peritoneal membrane were studied in a rat PD model. Methods Rats received 10 mL conventional PD fluid (PDF) daily, with or without the addition of unfractionated heparin (UFH) or low molecular weight heparin (LMWH) in the PDF (1 mg/10 mL intraperitoneally) via a mini access port. Untreated rats served as controls. After 5 weeks, a 90-minute functional peritoneal transport test was performed and tissues and peritoneal leukocytes were taken. Results PD treatment induced loss of ultrafiltration ( p < 0.01), a twofold increase in glucose absorption ( p < 0.03), increased urea transport ( p < 0.02), and loss of sodium sieving ( p < 0.03), which were also found in the PDF + heparin groups. Increased peritoneal cell influx and hyaluronan production ( p < 0.02) as well as an exchange of mast cells and eosinophils for neutrophils after PD treatment were observed in PD rats; addition of heparin did not affect those changes. Mesothelial regeneration, submesothelial blood vessel and matrix formation, and accumulation of tissue macrophages were seen in PD animals. Spindle-shaped vimentin-positive and cytokeratin-negative cells indicated either partial injury and denudation of mesothelial cells or epithelial-to-mesenchymal transition. Neither UFH nor LMWH affected any of these morphological changes. Conclusion Within 5 weeks, PD treatment induces a chronic inflammatory condition in the peritoneum, evidenced by high transport, leukocyte recruitment, tissue remodeling, and induction of spindle-shaped cells in the mesothelium. Addition of LMWH or UFH to the PDF did not prevent these adverse PDF-induced peritoneal changes.

Background/Aims: Oxidative damage has been reported to be involved in the pathophysiology of chronic kidney disease (CKD) as well as in the pathogenesis of cardiovascular complications of CKD patients. The aim of the present investigation was to evaluate the levels of plasma carbonyl formation, a sensitive marker of enhanced oxidative stress in predialysis, hemodialysis (HD) and peritoneal dialysis (PD) patients. Methods: Plasma samples from 20 apparently healthy control individuals and 127 CKD (stages 2, 3, 4, HD and PD) patients were evaluated by Western blot analysis for the estimation of the levels of protein carbonyl formation. Results: Albumin represented the main plasma carbonylated protein. Increasing carbonylation of albumin was detected along with the severity of CKD, reaching significance at stages 3 and 4 (p < 0.01, compared to healthy controls). The carbonylation of albumin was even higher in the plasma of HD patients (p < 0.001), while in PD patients it was not statistically significant compared to controls (p = 0.224). Conclusions: The data presented in this work indicate that oxidative stress in CKD patients gradually increased during the development of the disease. This stress is probably intensified during HD, but not in PD subjects.

BackgroundIn experimental peritoneal dialysis (PD) studies, the occurrence of peritonitis is a confounder in the interpretation of effects of chronic peritoneal exposure to dialysis solutions. Since fluid cannot be drained in most experimental PD models in the rat, it is impossible to diagnose peritonitis based on dialysate white blood cell counts. To study the value of serum markers for the presence of peritonitis, alpha-2-macroglobulin (α2M) and albumin were measured in rats with and without peritonitis after chronic exposure to dialysis solutions. To further investigate the time course of these markers in relation to the severity of peritonitis, nondialyzed rats were challenged with increasing numbers of bacteria and followed for 28 days.MethodsIn the first study, α2M and albumin were measured in rats exposed to glucose/lactate-based dialysis fluid before sacrifice. A comparison was made between animals with peritonitis, as judged from the presence of extensive infiltrates after sacrifice (gold standard) and/or clinical signs of peritonitis, or absence of peritonitis and infiltrates. In the second study, rats were intraperitoneally (IP) injected with 3 different concentrations of Staphylococcus aureus, and serum α2M and albumin were measured at various time points.ResultsIn the first study, serum α2M was higher and serum albumin was lower in animals with peritonitis compared to animals without peritonitis (both p < 0.05). In the second study, induction of α2M was clearly dependent on the inoculum concentration. Peak values of α2M were found at days 1 and 3. At all time points after inoculation, α2M was higher in all injected groups compared to the control group. Serum albumin values decreased in the highest inoculum group and remained decreased until 28 days after IP injection. Despite a low sensitivity, serum α2M >40 mg/L and albumin ConclusionsMeasurement of α2M and albumin once per month is an additional tool in the diagnosis of silent peritonitis in the chronic peritoneal exposure model in the rat. Levels of α2M >40 mg/L and albumin

We analyzed abnormalities in serum potassium ([K]) in 40 episodes of diabetic ketoacidosis (DKA)--6 episodes in peritoneal dialysis (PD) and 34 episodes in hemodialysis (HD)--and in 245 episodes of nonketotic hyperglycemia (NKH)--70 episodes in PD and 175 episodes in HD. Serum glucose ([Glu]) was 25 mmol/L or higher in all episodes. We compared the PD and HD hyperglycemic episodes separately for DKA and NKH. For DKA, [Glu] was 55.5 + 4.8 mmol/L in PD and 51.9 +/- 12.2 mmol/L in HD [p = nonsignificant (NS)], and [K] was 6.4 +/- 1.5 mmol/L in PD and 6.3 +/- 1.1 mmol/L in HD (p=NS). Also for DKA, [K] was 5.5 mmol/L or higher in 4 episodes (66.7%) in PD and in 26 episodes (76.5%) in HD (p=NS), and 6.0 mmol/L or higher in 3 episodes (50.0%) in PD and in 22 (episodes 64.7%) in HD (p=NS). For NKH, [Glu] was 39.4 +/- 14.7 mmol/L in PD and 37.8 +/- 12.4 mmol/L in HD (p=NS), and [K] was 4.3 +/- 0.9 mmol/L in PD and 5.1 +/- 0.8 mmol/L in HD (p < 0.001). Also for NKH, [K] was 5.5 mmol/L or higher in 7 episodes (10.0%) in PD and in 55 episodes (31.4%) in HD (p < 0.001), and 6.0 mmol/L or higher in 4 episodes (5.7%) in PD and in 31 episodes (17.7%) in HD (p = 0.023). Serum sodium, tonicity, urea, osmolality, creatinine, chloride and anion gap, and arterial blood pH and partial pressure of carbon dioxide did not differ between PD and HDfor either DKA or NKH episodes, but serum total carbon dioxide content was lower in PD than in HD DKA episodes (6.5 + 3.8 mmol/L vs. 9.5 + 2.8 mmol/L, p = 0.038), and higher in PD than in HD NKH episodes (22.5 + 6.0 mmol/L vs. 20.9 + 4.4 mmol/L, p = 0.004). Although PD and HD DKA episodes appear not to differ in [K], the mean [K] and the frequency of hyperkalemia are both lower in PD than in HD NKH episodes. Differences between PD and HD in acid-base balance and, probably, in other factors affecting [K] (such as mineralocorticoid metabolism and blood levels) may account for the differences in [K] between PD and HD NKH episodes. Adv Perit Dial

BACKGROUND: The formation of glucose degradation products (GDPs) and accumulation of advanced glycation end products (AGEs) partly contribute to the bioincompatibility of peritoneal dialysis fluids (PDF). Aminoguanidine (AG) scavenges GDPs and prevents the formation of AGEs.METHODS: In a peritoneal dialysis (PD) rat model, we evaluated the effects of the addition of AG to the PDF on microcirculation and morphology of the peritoneum, by intravital microscopy and quantitative morphometric analysis.RESULTS: AG-bicarbonate effectively scavenged different GDPs from PDF. Daily exposure to PDF for 5 weeks resulted in a significant increase in leucocyte rolling in mesenteric venules, which could be reduced for approximately 50% by addition of AG-bicarbonate (PCONCLUSION: The supplementation of either AG reduced a number of PDF-induced alterations in our model, emphasizing the involvement of GDPs and/or AGEs in the PDF-induced peritoneal injury.

♦ Objectives Mesothelial cell (MC) injury caused by continuous exposure to unphysiological peritoneal dialysis (PD) fluid and by episodes of peritonitis can eventually lead to peritoneal adhesions and peritoneal fibrosis. In the present study, we evaluated the possibility of using autologous genetically modified MCs for transplantation after the induction of peritoneal injury by acute inflammatory mediators or chronic instillation of PD fluid. ♦ Methods Rats were injected intraperitoneally either once with N-formyl-methionyl-leucyl-phenylalanine (fMLP), or thioglycollate, or PD fluid [ i.e., Dianeal (Baxter Healthcare, Deerfield, Illinois, USA) or Physioneal (Baxter, Nivelles, Belgium)], or chronically (up to 8 weeks) with Dianeal. From 2 to 48 hours later, animals were injected with syngeneic MCs genetically modified to express the LacZ reporter gene. Rats were sacrificed 2 days later and expression of β-galactosidase (β-Gal) was visualized by X-Gal staining of excised tissues. Quantification of the percent area of β-Gal–positive MCs on part of the parietal peritoneum was performed using computerized image analysis. ♦ Results The highest numbers of repopulated genetically modified MCs were observed 8 hours after a single thioglycollate injection, approximately 0.66% of a representative 2-cm2 area selected for study (corresponding to approximately 10% of the peritoneal surface). The number of genetically modified MCs found to repopulate the peritoneal surface following short-term injury varied with inflammatory mediator (thioglycollate > PD fluid > fMLP) and duration of exposure. No obvious difference's were observed between the two PD fluids tested. Reimplantation of syngeneic genetically modified MCs was also observed after chronic instillation of PD fluid. ♦ Conclusions These data demonstrate that transplanted genetically modified MCs repopulate the denuded areas on the peritoneal surface that were caused by acute or chronic inflammation. This technique opens possibilities of MC transplantation and gene therapy in order to prevent complications relevant to the continuous ambulatory PD setting.