High-volume hemofiltration does not protect human kidney endothelial and tubular epithelial cells from septic plasma-induced injury.

High volume hemofiltration (HVHF) could remove from plasma inflammatory mediators involved in sepsis-associated acute kidney injury (SA-AKI). The IVOIRE trial did not show improvements of outcome and organ dysfunction using HVHF. The aim of this study was to evaluate in vitro the biological effects of plasma of patients treated by HVHF or standard volume hemofiltration (SVHF). We evaluated leukocyte adhesion, apoptosis and functional alterations of endothelial cells (EC) and tubular epithelial cells (TEC). In vitro data were correlated with plasma levels of TNF-α, Fas-Ligand (FasL), CD40-Ligand (CD40L), von Willebrand Factor (vWF) and endothelial-derived microparticles. An experimental model of in vitro hemofiltration using LPS-activated blood was established to assess cytokine mass adsorption during HVHF or SVHF. Plasma concentrations of TNF-ɑ, FasL, CD40L and von Willebrand Factor (vWF) were elevated at the start (d1h0) of both HVHF and SVHF, significantly decreased after 6 h (d1h6), remained stable after 12 h (d1h12) and then newly increased at 48 h (d3h0). Plasma levels of all these molecules were similar between HVHF- and SVHF-treated patients at all time points considered. In addition, the levels of endothelial microparticles remained always elevated, suggesting the presence of a persistent microvascular injury. Plasma from septic patients induced leukocyte adhesion on EC and TEC through up-regulation of adhesion receptors. Moreover, on EC, septic plasma induced a cytotoxic and anti-angiogenic effect. On TEC, septic plasma exerted a direct pro-apoptotic effect via Fas up-regulation and caspase activation, loss of polarity, altered expression of megalin and tight junction molecules with an impaired ability to internalize albumin. The inhibition of plasma-induced cell injury was concomitant to the decrease of TNF-α, Fas-Ligand and CD40-Ligand levels. The protective effect of both HVHF and SVHF was time-limited, since a further increase of circulating mediators and plasma-induced cell injury was observed after 48 h (d3h0). No significant difference of EC/TEC damage were observed using HVHF- or SVHF-treated plasma. The in vitro hemofiltration model confirmed the absence of a significant modulation of cytokine adsorption between HVHF and SVHF. In comparison to SVHF, HVHF did not increase inflammatory cytokine clearance and did not reverse the detrimental effects of septic plasma-induced EC and TEC injury. Further studies using adsorptive membranes are needed to evaluate the potential role of high dose convective therapies in the limitation of the harmful activity of plasma soluble factors involved in SA-AKI.Trial registration IVOIRE randomized clinical trial; ClinicalTrials.gov (NCT00241228) (18/10/2005).

Protein-Bound Uremic Toxins and Inflammation Process in Hemodialysis Patients: Is There a Role for Adsorption Hemodiafiltration?

INTRODUCTION: Despite major advances in the field of dialysis, there are still some unmet needs such as reducing inflammation through adequate depuration. It is well known that the wide spectrum of pro-inflammatory and pro-atherosclerotic uremic toxins are inefficiently removed by current dialysis techniques. Adsorption seems to be an extra tool to remove toxins, but its effect and optimization have not been widely studied. The aim of this report was to present preliminary results regarding the possibility of performing hemodiafiltration with a highly adsorptive polymethylmethacrylate membrane. METHODS: The study was first conducted in 10 patients in which the safety and feasibility of hemodiafiltration with PMMA BG-U 2.1 membrane were tested through measurement of hemolysis indices, transmembrane pressures, and dialysis adequacy. Twenty patients were prospectively observed for 18-month period in which they consecutively underwent standard hemodialysis, standard post-dilution hemodiafiltration, and polymethylmethacrylate-based post-dilution hemodiafiltration. Protein-bound uremic toxins concentrations and inflammatory markers were measured throughout the observed period. RESULTS: HDF-PMMA was inferior to HDF in convective volume, but KT/V was similar, and no differences were noted in operating pressures during the two treatments. During HDF-PMMA period of treatment, we observed a significant reduction of CPR levels, and HDF-PMMA was superior to all other treatments in hepcidin removal even if this did not significantly affect hemoglobin levels. HDF-PMMA could significantly reduce indoxyl sulfate (indoxyl) concentration over a period of 6 months but not for p-cresyl sulfate (p-cresyl). CONCLUSION: PMMA BG-U 2.1 membrane can be safely and efficiently used in hemodiafiltration. Moreover, as these preliminary results show, adding adsorption properties to convection and diffusion enabled an increased removal of indoxyl uremic toxin associated to a reduction in inflammation markers as CRP and hepcidin without any negative impact on albumin levels.

Long-Term Bone Mineral Density Changes in Kidney Transplant Recipients Treated with Denosumab: A Retrospective Study with Nonequivalent Control Group.

Data on the effectiveness of denosumab on osteoporosis after kidney transplantation are limited. We investigated the long-term bone mineral density (BMD) changes in kidney transplant recipients (KTRs) treated with denosumab compared to untreated KTRs. We enrolled KTRs treated with denosumab 60 mg/6 months for 4 years. An untreated group of sex and age-matched KTRs with a 1:1 ratio was included. The primary outcome was BMD changes assessed by Dual-energy X-ray Absorptiometry over 4 years. Data on serum creatinine, alkaline phosphatase (ALP), parathyroid hormone, and 25-hydroxyvitamin D were collected. All patients received oral cholecalciferol and calcium supplementation. 23 denosumab-treated KTRs were enrolled, and 23 untreated KTRs. The median time from transplant to the start of denosumab was 4 years (range 0:24). The denosumab group showed a significant increase from baseline in BMD at the lumbar spine (LS) (9.0 ± 10.7%, p < 0.001), and total hip (TH) (3.8 ± 7.9%, p = 0.041). The untreated group showed a significant decrease at all sites (- 3.0 ± 7%, p = 0.041 at the LS; - 6.3 ± 9.2%, p = 0.003 at the TH; - 6.7 ± 9.3%, p = 0.003 at the FN). The between-group differences in percent BMD changes were statistically significant at all sites. Similar results were found for the respective Z-scores. The ALP serum levels significantly decreased from baseline only in the denosumab group, with a significant between-group difference (p = 0.032). No significant differences in serum creatinine, hypocalcaemic events or acute graft rejection rates were observed. Four years of denosumab therapy were associated with increased BMD in KTRs, while untreated KTRs showed significant BMD losses at all sites.

Role of the CD40-CD40 Ligand Pathway in Cardiovascular Events, Neurological Alterations, and Other Clinical Complications of Chronic Hemodialysis Patients: Protective Role of Adsorptive Membranes.

Despite the recent advances in dialysis technology, mortality rate of chronic uremic patients still remains excessively high: of note, in comparison to age- and sex-matched healthy controls, this frail population shows a higher incidence of infections, cancer, cognitive decline, and, in particular, major adverse cardiovascular events (MACE) that represent nowadays the first cause of mortality. Several traditional and nontraditional factors contribute to this increased risk for MACE and accelerated cellular senescence: among these, inflammation has been shown to play a key role. The costimulatory pathway CD40-CD40 Ligand (CD40L) is harmfully activated during inflammation and uremia-associated clinical complications: in particular, the soluble form of CD40L (sCD40L) can bind to the CD40 receptor triggering a cascade of detrimental pathways in immune and nonimmune cells. In this narrative review, we summarize the current concepts of the biological role of the CD40-CD40L pathway in uremia-associated organ dysfunction, focusing on the above-described main causes of mortality. Moreover, we discuss the interaction of the CD40-CD40L pathway with extracellular vesicles, microparticles recently identified as new uremic toxins. The biological effects of sCD40L in MACE, cognitive decline, infections, and cancer will be also briefly commented. Last, based on recent studies and ongoing clinical trials, we herein describe the modulatory activity of adsorptive dialysis membranes in polymethylmethacrylate on CD40-CD40L detrimental activation.

Intervention with EMDR on a sample of healthcare workers in the nephrology and dialysis service during the COVID-19 emergency: from immediate treatment effect to long-term maintenance.

Background: During the COVID-19 pandemic, psychological support was provided to healthcare workers in Nephrology and Dialysis Operative Unit of the Azienda Ospedaliera Bassini using an EMDR group protocol to decrease posttraumatic stress symptoms in the medium and long term. The aim of this study was to demonstrate the effectiveness of EMDR treatment to reduce post-traumatic stress symptoms at the end of the first pandemic wave and its progress over time in the subsequent phases of the health emergency. Methods: The sample of study consisted of 43 healthcare workers from the Nephrology and Dialysis Service who spontaneously decided to take part in the Brief EMDR treatment. Statistical analyses were carried out to compare the data collected with the IES-R, the Emotion Thermometer and the Post-Traumatic Growth Scale. The comparisons covered pre-treatment, post-treatment and follow-up. Results: The results show a significant clinical improvement in reducing PTSD symptoms following the Brief EMDR group treatment. The comparison between PRE and POST treatment (DELTA1) regarding the scores from IES-R and Emotion Thermometer, highlighted the important statistically change that occurred in terms of symptomatology reduction (p < 0.001). By comparing POST and FU (DELTA2), it was observed that all variables except avoidance show a significant weakening of the effect with time (p < 0.001), but the magnitude of this effect is much smaller than the improvement found in DELTA1. DELTA 3 analysis finally made it possible to highlight how the treatment effect is maintained almost intact at follow-up. In fact, the maintenance of a better situation at follow-up was observed, in the course of re-traumatization linked to the new wave, compared to the initial data (p < 0.001). Conclusion: The COVID-19 health emergency has significantly impacted hospital healthcare workers, leading to a high risk of developing PTSD symptoms. A psychological intervention aimed at the operators themselves is therefore of great importance.

The Next Evolution of HemoDialysis eXpanded: From a Delphi Questionnaire-Based Approach to the Real Life of Italian Dialysis Units.

INTRODUCTION: Impact assessment of new technologies in chronic hemodialysis (HD) is challenging due to HD patient frailty, the complexity of HD clinical trials and practice variability among countries. Among the most recent HD innovations, medium cut-off (MCO) dialyzers present an optimized membrane geometry that provides enhanced clearances for middle and large molecular weight uremic toxins (UT). These toxins are poorly cleared by available HD techniques and largely contribute to patient morbidity and mortality. The aim of this paper is to assess the available clinical evidence about MCO membranes and to identify the next steps needed to generate conclusive data on their use in HD. METHODS: With this purpose, we first reviewed and compared the current HD technologies aimed to improve the clearance of middle and large UT; subsequently, we used a Delphi questionnaire to identify and discuss the consensus about MCO efficacy within a large sample of the Italian Nephrology community. RESULTS AND CONCLUSIONS: Our investigation gathered a significant degree of consensus on the beneficial role of MCO membrane and expanded HD. Finally, we used our results to propose future trial designs and clinical investigations aimed to improve evidence quality about the use of these membranes in the present clinical scenario of dialysis units.

[Utility of computerized vascular access monitoring: a pilot study].

The surveillance of a vascular access (VA) is of primary importance for its outcome and for the patients' survival. However, there is still confusion about its usefulness, who should make it (physician or nurse) and when, and what is the best functional test to use. This retrospective analysis reports our experience of VA monitoring; it is based on the collaboration between concept doctors and nurses and on parameters integration, realized with the help of a software for vascular access monitoring (SMAV) designed by us. The analysis confronts the data gathered on a group of 100 patients, 13 months before the adoption of the SMAV, and another 100 patients, 19 months after. Of these patients, 13 belonged to both groups and were "controls of themselves". The number of thrombosis and angioplasties (PTA) plummeted in the 19 months in which the SMAV was used, from 10 (10%; 0.008 thrombosis/patient month) to 1 (1%; 0.0005 thrombosis/patient month) (p <0.01) and from 49 (49%; 0.037 PTA/patient month) to 27 (27%; 0.014PTA/patient month) (p <0.05) respectively. In the 13 control patients, a reduction of 70% in the number of PTA (from 26 to 8) was observed. SMAV allowed us to integrate the many functional parameters, making it easy to share information, encouraging teamwork, strengthening professional skills, and favouring the best management of AVs. The result was a reduction in thrombotic events and, surprisingly, a reduction of the need for PTA, most likely thanks to the higher level of attention in the evaluation and puncture of AV.

Belimumab may decrease flare rate and allow glucocorticoid withdrawal in lupus nephritis (including dialysis and transplanted patient).

BACKGROUND: Belimumab (Benlysta) is currently approved for the treatment of active Lupus despite standard therapy. Few data are available on the efficacy of this drug in lupus nephritis (LN). METHODS: 17 LN female followed in two Nephrology Italian Unit received belimumab for a median period of 36 months (range 6-42 months). The indications were: arthralgia in 3 patients, cutaneous manifestations in 2, residual proteinuria in 8, and the need to reduce steroids for severe side effects in 4. Of interest, 1 patient started therapy during Peritoneal Dialysis and continued after kidney transplantation due to non-responsive arthralgias. RESULTS: Arthralgia and skin manifestations resolved in all patients. Proteinuria normalized in three patients and stabilized in all but one of the others. Steroids were indefinitely stopped in six patients (35%) and reduced to around 40% of the basal dosage in the other patients. During belimumab therapy, three extrarenal and one renal SLE flares were diagnosed accounting for a rate of renal flares of 0.02/patient/year. No major adverse events leading to therapy withdrawal occurred. CLINICAL CASE: Arthralgia resolved, immunological parameters improved and prednisone could be reduced within few months in the patient who started belimumab during peritoneal dialysis. After kidney transplantation belimumab was stopped but due to arthralgias unresponsive to standard immunosuppressive therapy it was restarted with success. CONCLUSIONS: Belimumab allows the achievement of complete response together with the withdrawal or the reduction of corticosteroids in almost all our patients. Of interest its satisfactory use in a patient in peritoneal dialysis and after kidney transplantation.

Recurrent intradialytic paroxysmal atrial fibrillation: hypotheses on onset mechanisms based on clinical data and computational analysis.

Atrial fibrillation (AF) incidence is high in end-stage renal disease (ESRD) patients, and haemodialysis (HD) session may induce paroxysmal AF episodes. Structural atrium remodelling is common in ESRD patients, moreover, HD session induces rapid plasma electrolytes and blood volume changes, possibly favouring arrhythmia onset. Therefore, HD session represents a unique model to study in vivo the mechanisms potentially inducing paroxysmal AF episodes. Here, we present the case report of a patient in which HD regularly induced paroxysmal AF. In four consecutive sessions, heart rate variability analysis showed a progressive reduction of low/high frequency ratio before the AF onset, suggesting a relative increase in vagal activity. Moreover, all AF episodes were preceded by a great increase of supraventricular ectopic beats. We applied computational modelling of cardiac cellular electrophysiology to these clinical findings, using plasma electrolyte concentrations and heart rate to simulate patient conditions at the beginning of HD session (pre-HD) and right before the AF onset (pre-AF), in a human atrial action potential model. Simulation results provided evidence of a slower depolarization and a shortened refractory period in pre-AF vs. pre-HD, and these effects were enhanced when adding acetylcholine effect. Paroxysmal AF episodes are induced by the presence of a trigger that acts upon a favourable substrate on the background of autonomic nervous system changes and in the described case report all these three elements were present. Starting from these findings, here we review the possible mechanisms leading to intradialytic AF onset.

A case series of chronic haemodialysis patients: mortality, sudden death, and QT interval.

AIMS: A high prevalence of prolonged QT interval duration has been observed among haemodialysis (HD) patients. The aim of this cases series was to describe the association of various risk factors with total mortality and sudden cardiac death (SCD) in this population. METHODS AND RESULTS: One hundred and twenty-two patients undergoing HD, [median: age 71.3 years [interquartile ratio (IQR) 62.9-76.6], HD duration 3.0 years (IQR 1.3-7.8) and 64.8% male], of which 37.7% with ischaemic cardiac disease, 41.8% with dilated cardiomyopathy (DC), 84.4% with hypertension, and 27.1% with diabetes, were studied. Median left ventricular ejection fraction (LVEF) was 60.0% (IQR 52-64) and left ventricular mass index (LVMI) was 147.3 g/m(2) (IQR 128.0-179.9). QT interval duration corrected for heart rate (QTc) was measured by electrocardiogram Holter recording and considered prolonged when longer than 450 ms in men and 460 ms in women. Forty-four patients (36.0%) had a prolonged QTc. Female gender (P < 0.001) and DC (P = 0.018) were associated with a longer QTc, while LVEF (P = 0.012) was inversely related. During the study period (median follow-up 3.9 years), 51 patients died (41.8%), of whom 12 died for SCD. In multivariate analysis age at recruitment [HR = 1.07, 95% confidence interval (CI): 1.03-1.11, P < 0.001], prolonged QTc (HR = 2.16, 95% CI: 1.20-3.91, P = 0.011) and presence of DC (HR = 3.75, 95% CI: 1.01-7.00, P < 0.001) were independently associated with total mortality, while only a prolonged QTc (HR = 8.33, 95% CI: 1.71-40.48, P = 0.009) and increasing LVMI (HR = 1.01, 95% CI: 1.00-1.02, P = 0.022) were associated with SCD. CONCLUSIONS: In a case series of HD patients, QTc was associated with total mortality and SCD. Further studies to test this hypothesis in a larger population are necessary.

Alterations of atrial electrophysiology related to hemodialysis session: insights from a multiscale computer model.

BACKGROUND: The prevalence of atrial fibrillation is increased in patients with end-stage renal disease. Previous studies suggested that extracellular electrolyte alterations caused by hemodialysis (HD) therapy could be proarrhythmic. METHODS: Multiscale models were used for a consequent analysis of the effects of extracellular ion concentration changes on atrial electrophysiology. Simulations were based on measured electrolyte concentrations from patients with end-stage renal disease. RESULTS: Simulated conduction velocity and effective refractory period are decreased at the end of an HD session, with potassium having the strongest influence. P-wave is prolonged in patients undergoing HD therapy in the simulation as in measurements. CONCLUSIONS: Electrolyte concentration alterations impact atrial electrophysiology from the action potential level to the P-wave and can be proarrhythmic, especially because of induced hypokalemia. Analysis of blood electrolytes enables patient-specific electrophysiology modeling. We are providing a tool to investigate atrial arrhythmias associated with HD therapy, which, in the future, can be used to prevent such complications.

Peritoneal dialysis fluid bioincompatibility and new vessel formation promote leukocyte-endothelium interactions in a chronic rat model for peritoneal dialysis.

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.

Alterations of atrial electrophysiology induced by electrolyte variations: combined computational and P-wave analysis.

AIMS: Haemodialysis (HD) therapy represents a unique model to test in vivo, in humans, the effects of changes in plasma ionic concentrations. Episodes of paroxysmal atrial fibrillation (AF) often occur during the treatment. We investigated the effects of HD-induced electrolyte variations on atrial electrophysiology by analysing ECG P-wave duration (PWd), which reflects atrial conduction velocity (CV), and simulated atrial action potential (AP). METHODS AND RESULTS: In 20 end-stage renal disease patients PWd (signal-averaged ECG), heart rate (HR), blood pressure, Na(+), K(+), Ca(2+), and Mg(2+) plasma concentrations were measured before and after HD session. The Courtemanche computational model of human atrial myocyte was used to simulate the atrial AP. AP upstroke duration (AP(ud)), AP duration and atrial cell effective refractory period (ERP) were computed. Extracellular electrolyte concentrations and HR were imposed to the average values measured in vivo. HD decreased K(+) (from 4.9 +/- 0.5 to 3.9 +/- 0.4 mmol/L, P < 0.001) and Mg(2+) (0.92 +/- 0.08 to 0.86 +/- 0.05 mmol/L, P < 0.05), and increased Na(+) (139.8 +/- 3.4 to 141.6 +/- 3.1 mmol/L, P < 0.05) and Ca(2+) (1.18 +/- 0.09 to 1.30 +/- 0.07 mmol/L, P < 0.001) plasma concentrations. PWd systematically increased in all the patients after HD (131 +/- 11 to 140 +/- 12 ms, P < 0.001), indicating an intra-atrial conduction slowing. PWd increments were inversely correlated with K(+) variations (R = 0.73, P < 0.01). Model-based analysis indicated an AP(ud) increase (from 2.58 to 2.94 ms) after HD, coherent with experimental observations on PWd, and a reduction of ERP by 12 ms. CONCLUSION: Changes of plasma ionic concentrations may lead to modifications of atrial electrophysiology that can favour AF onset, namely a decrease of atrial CV and a decrease of atrial ERP.

Celecoxib treatment reduces peritoneal fibrosis and angiogenesis and prevents ultrafiltration failure in experimental peritoneal dialysis.

BACKGROUND: Daily peritoneal exposure to peritoneal dialysis fluid (PDF) induces severe morphological alterations including fibrosis and angiogenesis that lead to a loss of peritoneal ultrafiltration (UF) capacity. Since cyclooxygenase (COX)-2 is involved in fibrosis and angiogenesis, we investigated the in vivo effects of a selective COX-2 inhibitor (celecoxib) in a rat-PD model. METHODS: Sixteen rats daily received 10 ml of conventional PDF for 4-5 weeks intraperitoneally. Half of them (n = 8) daily received celecoxib (20 mg/kg BW) via oral gavage, and the other half (n = 8) received vehicle via oral gavage. The study also included two control groups (no PDF instillations), each consisting of n = 8 animals that daily received celecoxib or vehicle, respectively, via oral gavage. Functional, morphological and cellular parameters were analysed. RESULTS: PDF exposure induced an inflammatory condition evidenced by the increased leucocyte number and synthesis of MCP-1, VEGF and hyaluronic acid. After PDF exposure, the omentum showed intense angiogenesis and milky spots formation. Parietal peritoneum showed increased angiogenesis, lymphangiogenesis, submesothelial matrix thickness and enhanced expression of mesothelial aquaporin1 (Aqp1). Concomitant PDF and celecoxib exposure drastically reduced PGE2 levels, angiogenesis, lymphangiogenesis, fibrosis and milky spot formation in studied tissues, but did not modify mesothelial Aqp1 expression nor the tissue expression of VEGF and inflammatory markers. PDF exposure induced severe UF failure that celecoxib treatment completely prevented. CONCLUSIONS: Altogether, celecoxib treatment improves UF capacity and reduces morphological alterations in our rat PD model.

The first weeks on peritoneal dialysis: effects on clinical parameters.

Initiation of peritoneal dialysis (PD) induces several changes both locally in the peritoneum and systemically. We performed a pilot study to generate insights into the early clinical and systemic changes after catheter insertion and the first weeks of PD. The study included 11 new PD patients (7 men, 4 women). The study period started just before implantation of the Tenckhoff catheter and finished 6 weeks after the start of PD. All patients were treated with lactate-buffered dialysis solutions. Clinical parameters, routine laboratory tests and markers of systemic inflammation were determined. The mean (+/- standard deviation) age of the patients was 52.6 +/- 12.1 years, mean weight was 81.3 +/- 14.7 kg, and mean blood pressure was 143.3/ 87.8 +/- 18.5/8.2 mmHg. Weight and blood pressure did not change significantly during the first weeks of PD. Throughout the study, 24-hour urine production declined by 6.9 mL/day (p = 0.006). Daily residual creatinine clearance (CCr) decreased by 0.036 mL/min (p = 0.008). High-sensitivity C-reactive protein (hs-CRP) was significantly higher in patients who had undergone hemodialysis before the start of the study (p < 0. 0001) and declined during the study in that group (p = 0.001). No significant change in hs-CRP was found in the group that started dialysis with PD. In this pilot study, we found no significant changes in the clinical parameters of weight and blood pressure during the first weeks of PD. However, urine production and residual CCr declined significantly during the study period, starting from the moment of catheter insertion. Levels of the systemic inflammatory marker hs-CRP were higher in patients who had previously undergone hemodialysis; its level in those patients decreased after hemodialysis ended.

Differences in heart rate variability during haemodialysis and haemofiltration.

BACKGROUND: The aim of our study was to evaluate whether convective (haemofiltration, Hf) and diffusive (haemodialysis, Hd) dialysis techniques induce different patterns of long- and short-term autonomic adjustments in haemodynamically stable dialysis patients. METHODS: Ten haemodynamically stable Hd patients were studied. Each patient underwent a block of six Hd sessions, then was switched to six Hf. During the last session of each dialytic treatment, continuous beat to beat measurements of systolic arterial pressure (SAP) and heart rate (HR) were performed. Spectral analysis of heart rate variability (HRV) was made before and during the treatment to evaluate the modification of autonomic nervous system activity. RESULTS: Baseline values of plasma sodium, body weight, HR and SAP were not different for the two considered methods of dialysis, while the baseline values of normalized LF were significantly higher in Hf as compared to Hd and the opposite was observed for HF powers (P < 0.001). Sodium balance and body weight loss per hour did not differ between Hd and Hf while body temperature was kept constant in all sessions. Throughout the dialytic procedures, with both techniques, SAP was constant, while HR diminished from the first hour till the end of the procedure (P < 0.05). An increase in LF (and decrease in HF) was noticed only in the case of Hd, considering normalized units (P < 0.05). These selective changes were maintained also during the recovery after the procedure. CONCLUSIONS: The spectral analysis of RR interval variability during Hd and Hf suggests a potential autonomic advantage with Hf, to be added to the well-recognized intrinsic greater haemodynamic stability.

Novel role for mast cells in omental tissue remodeling and cell recruitment in experimental peritoneal dialysis.

Because of its dynamic structure, the omentum plays a key role in the immunity of the peritoneal cavity by orchestrating peritoneal cell recruitment. Because mast cells accumulate in the omentum upon experimental peritoneal dialysis (PD) and may produce angiogenic/profibrotic factors, it was hypothesized that mast cells mediate omental tissue remodeling during PD. Daily treatment with conventional PD fluid (PDF) for 5 wk resulted in a strong omental remodeling response, characterized by an approximately 10-fold increase in mast cell density (P < 0.01), an approximately 20-fold increase in vessel density (P < 0.02), an approximately 20-fold increase in the number of milky spots (P < 0.01), and a four-fold increase in submesothelial matrix thickness (P < 0.0003) in wild-type rats. In contrast, all PDF-induced omental changes were significantly reduced in mast cell-deficient Ws/Ws rats or in wild-type rats that were treated orally with a mast cell stabilizer cromoglycate. A time-course experiment showed mast cell accumulation immediately before the formation of blood vessels and milky spots. Functionally, PDF evoked a peritoneal cell influx, which was significantly reduced in Ws/Ws rats (P < 0.04) and in wild-type rats that were treated with cromoglycate (P < 0.03). Cromoglycate treatment also completely prevented PDF-induced omental adhesions to the catheter tip (P = 0.0002). Mesothelial damage, angiogenesis, and fibrosis of mesentery and parietal peritoneum as well as glucose absorption rate and ultrafiltration capacity proved to be mast cell independent. Data strongly support the hypothesis that mast cells mediate PDF-induced omental tissue remodeling and, subsequently, peritoneal cell influx and adhesion formation, providing therapeutic possibilities of modulating omental function.

Peritoneal exposure model in the rat as a tool to unravel bio(in)compatibility of PDF.

Patients treated with peritoneal dialysis (PD) are at risk for development of ultrafiltration failure and peritonitis. The relative unphysiologic composition of the currently used peritoneal dialysis fluids (PDF) is a major cause for the development of morphologic changes of the peritoneal membrane such as fibrosis and new vessel formation, ultimately resulting in ultrafiltration failure. In recent years, a major research focus has become the development of new and improved PDF. Typically, the first phase of biocompatibility testing of new PDF involves in vitro testing, using cell culture systems such as primary mesothelial cells or peritoneal macrophages. In vivo studies using animal models permit the analysis of biocompatibility under conditions that allow for cell-to-cell interactions and dynamic changes in solution composition that more closely mimic the clinical situation. In this paper, we will review the applicability of a peritoneal exposure model in the rat to study PDF biocompatibility-related issues.