Cyclosporine A-Induced Conchal Hyperplasia with Nasal Obstruction in a Patient with Membranous Nephropathy.

BACKGROUND The immunomodulatory and pharmacokinetic effects of cyclosporine A are used to treat diverse disease entities in different medical fields, including organ transplantation and/or autoimmune diseases. It is also applied in patients with nephrotic range proteinuria as an adjunct to steroids and supportive antihypertensive/antiproteinuric medications. Cyclosporine has a small therapeutic window and is dosed with respect to the underlying disease entity and severity via trough level adaptations. Among its most frequent adverse effects are hypertension, nephrotoxicity, neurotoxicity, and electrolyte disturbances. Hypertrichosis and gingival hyperplasia are obvious and widely recognized adverse effects. CASE REPORT We report on a 66-year-old woman who was treated with cyclosporine A for primary membranous nephropathy. During treatment with cyclosporine, she developed hirsutism and gingival hyperplasia. Later, she reported having impaired nasal breathing and dyspnea on mild physical exercise. Clinical, rhinoscopic, and radiological evaluations showed marked conchal hyperplasia as a potential cause of her symptoms. An extensive medical work-up did not show evidence of allergic, immunologic, or other drug adverse effects, suggesting cyclosporine-induced hyperplasia of the turbinates as a hypothetical causative factor. Dose reductions did not lead to resolution of symptoms but resulted in increasing proteinuria. Therefore, cyclosporine was stopped, and the patient was treated with rituximab. Thereafter, hirsutism and gingival and conchal hyperplasia gradually regressed over 2-4 months, showing complete resolution of conchal hyperplasia on computed-tomography follow-up after 6 months. CONCLUSIONS Cyclosporine can not only result in gingival hyperplasia but also in hyperplasia of the turbinates leading to impaired nasal breathing and shortness of breath on exertion. An extensive search for many other known causes of conchal swelling is warranted to finally suggest an adverse effect of cyclosporine. Discontinuation of cyclosporine resulted in complete remission of conchal hyperplasia as well as other adverse effects.

Effect of Third and Fourth mRNA-Based Booster Vaccinations on SARS-CoV-2 Neutralizing Antibody Titer Formation, Risk Factors for Non-Response, and Outcome after SARS-CoV-2 Omicron Breakthrough Infections in Patients on Chronic Hemodialysis: A Prospective Multicenter Cohort Study.

The aim of this study is to determine the effect of repeated vaccinations on neutralizing SARS-CoV-2 IgG antibody titers, evaluate risk factors for immunological non-response, and to report breakthrough infections in chronic hemodialysis patients. METHODS: A prospective, multi-center cohort study in 163 chronic hemodialysis patients was conducted. Antibody titers were measured three months after second, third, and fourth (10 pts) booster vaccinations. SARS-CoV-2 neutralizing antibody titers in BAU/mL and % inhibition were divided into three categories (<216, 216-433, >433 and <33, 33-66, and >66%). Somers's test, paired t-test, and univariable and multivariable logistic regression analysis were applied to evaluate differences in antibody levels and search for risk factors for vaccination failure defined as neutralizing titers <50% and/or need for repeated booster vaccinations. Furthermore, we report on a case series to describe characteristics of patients after four vaccinations (n = 10) and breakthrough infections (n = 20). RESULTS: Third dose boosters resulted in higher proportions of patients with neutralizing antibody levels >66% as compared to after the second dose (64.7% after second dose vs. 88.9% after third dose, p = 0.003), as well as in a respective increase in neutralizing titer levels in % from 68 ± 33% to 89 ± 24 (p <0.001). The proportion of patients with IgG-titers below 216 BAU/mL decreased from 38.6 to 10.5% (p ≤ 0.001). Age (p = 0.004, OR 1.066, 95% CI 1.020-1.114) and presence of immunosuppressive medications (p = 0.002, OR 8.267, 95% CI 2.206-30.975) were identified as major risk factors for vaccination failure. Repeated booster vaccinations ≥4 times were effective in 8 out of 10 former low-responders (80%) without any side effects or safety concerns. Breakthrough infections showed a clinically mild course but were associated with prolonged viral shedding on PCR-testing ranging 7-29 (mean 13) days. CONCLUSIONS: Third and fourth mRNA-based booster vaccinations resulted in higher and longer lasting SARS-CoV-2 antibody levels as compared to after two dosages. The presence of immunosuppressive medication and repeat vaccinations are major potentially modifiable measures to increase antibody levels in non-or low-responders. Breakthrough infections with SARS-CoV-2 Omicron were associated with prolonged viral shedding but clinically mild disease courses.

Angiogenic Role of Mesothelium-Derived Chemokine CXCL1 During Unfavorable Peritoneal Tissue Remodeling in Patients Receiving Peritoneal Dialysis as Renal Replacement Therapy.

Peritoneal dialysis (PD) is a valuable 'home treatment' option, even more so during the ongoing Coronavirus pandemic. However, the long-term use of PD is limited by unfavourable tissue remodelling in the peritoneal membrane, which is associated with inflammation-induced angiogenesis. This appears to be driven primarily through vascular endothelial growth factor (VEGF), while the involvement of other angiogenic signaling pathways is still poorly understood. Here, we have identified the crucial contribution of mesothelial cell-derived angiogenic CXC chemokine ligand 1 (CXCL1) to peritoneal angiogenesis in PD. CXCL1 expression and peritoneal microvessel density were analysed in biopsies obtained by the International Peritoneal Biobank (NCT01893710 at www.clinicaltrials.gov), comparing 13 children with end-stage kidney disease before initiating PD to 43 children on chronic PD. The angiogenic potential of mesothelial cell-derived CXCL1 was assessed in vitro by measuring endothelial tube formation of human microvascular endothelial cells (HMECs) treated with conditioned medium from human peritoneal mesothelial cells (HPMCs) stimulated to release CXCL1 by treatment with either recombinant IL-17 or PD effluent. We found that the capillary density in the human peritoneum correlated with local CXCL1 expression. Both CXCL1 expression and microvessel density were higher in PD patients than in the age-matched patients prior to initiation of PD. Exposure of HMECs to recombinant CXCL1 or conditioned medium from IL-17-stimulated HPMCs resulted in increased endothelial tube formation, while selective inhibition of mesothelial CXCL1 production by specific antibodies or through silencing of relevant transcription factors abolished the proangiogenic effect of HPMC-conditioned medium. In conclusion, peritoneal mesothelium-derived CXCL1 promotes endothelial tube formation in vitro and associates with peritoneal microvessel density in uremic patients undergoing PD, thus providing novel targets for therapeutic intervention to prolong PD therapy.

A Rare Cause of Left Shoulder Pain in a Peritoneal Dialysis Patient.

BACKGROUND Non-specific pain of connective tissues and joints is one of the most frequently expressed patient concerns in everyday practice. The most common cause is osteo-degenerative changes in the cartilage and/or joint system. Metastatic calcification is a rare and initially often overlooked cause of persistent, therapy-resistant pain of connective tissues and joint apparatus in end-stage renal disease (ESRD) patients on dialysis therapy. These calcifications are induced by persistent hyperphosphatemia/hyperparathyroidism and can occur in various organs, including joints, tendons, heart valves, soft tissues, and blood vessels. CASE REPORT We report on a 46-year-old male patient with ESRD due to cANCA-associated systemic vasculitis. The patient evolved unfavorably to end-stage renal failure and started continuous ambulatory peritoneal dialysis (CAPD). Four years after initiation of CAPD, the patient reported having painful motion of the left shoulder, and symptomatic physiotherapy and non-steroidal-anti-inflammatory-drugs (NSAIDs) were prescribed. An X-ray examination of the left shoulder showed severe periarticular calcifications. Repeated nutritional counselling was offered, and intensive phosphate-binder therapy was administered, resulting in a reduction in phosphate levels from 2.10 mmol at the time of diagnosis to 1.26 mmol/l 16 months later. Radiological reevaluation showed a near complete resolution of the periarticular calcifications. CONCLUSIONS Metastatic calcifications may arise in ESRD patients despite only moderately elevated blood phosphate levels. Intensive measures to reduce the phosphate load to normal levels should be implemented and can lead to almost complete resolution of ectopic calcifications in affected patients.

[Present practise patterns of renal replacement therapy in German intensive care medicine]. / Aktueller Stand der Durchführung von Nierenersatztherapien auf deutschen Intensivstationen.

About 50% of all critically ill patients develop acute kidney injury (AKI) and approximately 15% receive renal replacement therapy (RRT). Although RRT is frequently used in intensive care units in Germany, it is currently unknown which RRT procedures are available, which qualification the involved staff has, which anticoagulation strategies are used and how RRT doses are prescribed. To investigate quality and structural characteristics of the performance of RRT in intensive care units throughout Germany, the German Interdisciplinary Society of Intensivists (Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin [DIVI]) performed an inquiry among their members. A total of 897 members participated in the survey in which practical aspects were queried. In 69.1% of the cases, RRT was performed in hospitals with more than 400 beds and in 74.5% in university hospitals or other primary care hospitals. Furthermore, 93.3% of clinics are equipped with continuous and 75.8% with intermittent renal replacement devices. In 91.9%, indication for initiation of RRT was performed by trained physicians specialized in intensive care medicine or nephrologists. Intermittent as well as continuous modalities are both present in three-quarters of cases, which allows for individualized therapy. However, the documentation of dialysis dose needs to be improved.

Lactate-Based Scoring System in the Diagnosis of Necrotizing Fasciitis.

Necrotizing fasciitis (NF) is a rare and quickly progressing infection and leads to 100% mortality if untreated. Quick diagnosis and an early and radical surgical treatment are essential for stopping bacterial progression. Unfortunately, the absence of clear clinical signs makes the diagnosis often challenging. Therefore, we searched for easy determinable predictive laboratory markers for NF. This is the first study which includes lactate values in a new score. A retrospective analysis of patients with NF (n = 44) and patients with erysipelas (n = 150) was performed. Lactate values, patients' demographics, clinical presentations, site of infection, comorbidities, microbiological and laboratory findings, antibiotic therapies, and LRINEC and modified LRINEC scores were analyzed. Logistic regression analysis was used to derive adjusted weights, and final simple point score was assessed with a ROC curve analysis. Patients with NF had a mean age of 57 years and patients with erysipelas 65 years. The median hospital length of stay was 8 and 49 days in patients with erysipelas and NF, respectively. Although only one patient (0.7%) in the group of erysipelas died, the mortality rate of patients with NF was 9/44 (20.5%). The lactate values were statistically significant higher in the NF group, 4.1 vs 2.0 mmol/l (P < .001). The new created CologNe-FaDe-score shows the highest AUC-value with 0.907. With the help of lactate values, the CologNe-FaDe-score consists of easily practicable and highly available parameters, which could sensitize diagnosis.

Efficacy and Safety of Vilobelimab (IFX-1), a Novel Monoclonal Anti-C5a Antibody, in Patients With Early Severe Sepsis or Septic Shock-A Randomized, Placebo-Controlled, Double-Blind, Multicenter, Phase IIa Trial (SCIENS Study).

Anaphylatoxin C5a, a proinflammatory complement split product, plays a central role in mediating organ dysfunction. OBJECTIVES: This phase II clinical trial was conducted to study safety, tolerability, pharmacokinetics, and pharmacodynamics of vilobelimab, a recombinant monoclonal antibody against C5a, in patients with severe sepsis or septic shock. DESIGN: Multicenter, randomized, and placebo-controlled study. SETTING AND PARTICIPANTS: Eleven multidisciplinary ICUs across Germany. Adult patients with severe sepsis or septic shock and with early onset of infection-associated organ dysfunction. MAIN OUTCOMES AND MEASURES: Patients were randomly assigned in a ratio of 2:1 to three subsequent dosing cohorts for IV vilobelimab or placebo receiving either 2 × 2 mg/kg (0 and 12 hr), 2 × 4 mg/kg (0 and 24 hr), and 3 × 4 mg/kg (0, 24, and 72 hr). Co-primary endpoints were pharmacodynamics (assessed by C5a concentrations), pharmacokinetics (assessed by vilobelimab concentrations), and safety of vilobelimab. Preliminary efficacy was evaluated by secondary objectives. RESULTS: Seventy-two patients were randomized (16 patients for each vilobelimab dosing cohort and eight patients for each placebo dosing cohort). Vilobelimab application was associated with dosing dependent decrease in C5a compared with baseline (p < 0.001). Duration of C5a decrease increased with more frequent dosing. Membrane attack complex lysis capacity measured by 50% hemolytic complement was not affected. Vilobelimab was well tolerated with similar safety findings in all dose cohorts. No vilobelimab-specific adverse events emerged. For vilobelimab-treated patients, investigators attributed less treatment-emergent adverse events as related compared with placebo. Dosing cohorts 2 and 3 had the highest ICU-free and ventilator-free days. There was no difference in mortality, vasopressor-free days, or renal replacement therapy-free days between the groups. CONCLUSIONS AND RELEVANCE: Administration of vilobelimab in patients with severe sepsis and septic shock selectively neutralizes C5a in a dose-dependent manner without blocking formation of the membrane attack complex and without resulting in detected safety issues. The data warrant further investigation of C5a inhibition in sepsis.

Hashimoto's Thyroiditis-Associated Acute Renal Failure and Pitfalls of eGFR Interpretation in Thyroid Diseases.

The authors describe a patient with severe hypothyroidism due to Hashimoto's thyroiditis and describe the pitfalls of estimated glomerular filtration rate interpretation in such cases. LEARNING POINTS: Manifest hypothyroidism can lead to a functional reduction in glomerular filtration rates (GFRs).Restoration of a normal thyroid stimulating hormone (TSH) will also restore kidney function.Cystatin C-based GFR formulas will overestimate renal filtration rates in cases of hypothyroidism and underestimate GFRs in cases of hyperthyroidism.

Validation of a Prospective Urinalysis-Based Prediction Model for ICU Resources and Outcome of COVID-19 Disease: A Multicenter Cohort Study.

In COVID-19, guidelines recommend a urinalysis on hospital admission as SARS-CoV-2 renal tropism, post-mortem, was associated with disease severity and mortality. Following the hypothesis from our pilot study, we now validate an algorithm harnessing urinalysis to predict the outcome and the need for ICU resources on admission to hospital. Patients were screened for urinalysis, serum albumin (SA) and antithrombin III activity (AT-III) obtained prospectively on admission. The risk for an unfavorable course was categorized as (1) "low", (2) "intermediate" or (3) "high", depending on (1) normal urinalysis, (2) abnormal urinalysis with SA ≥ 2 g/dL and AT-III ≥ 70%, or (3) abnormal urinalysis with SA or AT-III abnormality. Time to ICU admission or death served as the primary endpoint. Among 223 screened patients, 145 were eligible for enrollment, 43 falling into the low, 84 intermediate, and 18 into high-risk categories. An abnormal urinalysis significantly elevated the risk for ICU admission or death (63.7% vs. 27.9%; HR 2.6; 95%-CI 1.4 to 4.9; p = 0.0020) and was 100% in the high-risk group. Having an abnormal urinalysis was associated with mortality, a need for mechanical ventilation, extra-corporeal membrane oxygenation or renal replacement therapy. In conclusion, our data confirm that COVID-19-associated urine abnormalities on admission predict disease aggravation and the need for ICU (ClinicalTrials.gov number NCT04347824).

[Quality improvement measures in the care of critically ill intensive care patients with renal replacement therapy for acute kidney injury : Position paper of the Kidney Section of DIVI in collaboration with DGAI and DGIIN]. / Qualitätsverbessernde Maßnahmen in der Versorgung von kritisch kranken Intensivpatienten mit Nierenersatztherapie bei akuter Nierenschädigung : Positionspapier der Sektion Niere der DIVI unter Mitarbeit von DGAI und DGIIN.

Renal replacement therapy is after mechanical ventilation one of the most important and frequently used organ replacement therapies in daily routine intensive care practice. In contrast to mechanical ventilation, quality standards for renal replacement therapy are less well known and defined. In this position paper of the German Interdisciplinary Association for Intensive Care and Emergency Medicine, we describe quality standards of renal replacement procedures in order to improve therapy of patients with severe acute kidney injury.

CytoResc - "CytoSorb" Rescue for critically ill patients undergoing the COVID-19 Cytokine Storm: A structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: Approximately 8 - 10 % of COVID-19 patients present with a serious clinical course and need for hospitalization, 8% of hospitalized patients need ICU-treatment. Currently, no causal therapy is available and treatment is purely supportive. The main reason for death in critically ill patients is acute respiratory failure. However, in a number of patients a severe hyperinflammatory response with excessively elevated proinflammatory cytokines causes vasoplegic shock resistant to vasopressor therapy. A new polystyrene-based hemoadsorber (CytoSorb®, Cytosorbents Inc., New Jersey, USA) has been shown to adsorb effectively cytokines and other middle molecular weight toxins this way reducing their blood concentrations. This has been routinely used in clinical practice in the EU for other conditions where a cytokine storm occurs and an observational study has just been completed on COVID-19 patients. We hypothesized that the extracorporeal elimination of cytokines in critically ill COVID-19 patients with suspected hyperinflammation and shock may stabilize hemodynamics and improve outcome. The primary endpoint is time until resolution of vasoplegic shock, which is a well implemented, clinically relevant endpoint in critical care studies. TRIAL DESIGN: Phase IIb, multicenter, prospective, open-label, randomized, 1:1 parallel group pilot study comparing the additional use of "CytoSorb" to standard of care without "CytoSorb". PARTICIPANTS: Patients are recruited from the Intensive Care Units (ICUs) of 7 participating centers in Germany (approximately 10 ICUs). All patients aged 18- 80 with positive polymerase chain reaction (PCR) test for SARS-CoV-2, a C-reactive protein (CRP) ≥ 100 mg/l, a Procalcitonin (PCT) < 2 ng/l, and suspected cytokine storm defined via a vasoplegic shock (Norepinephrine > 0.2 µg/min/kg to achieve a Mean Arterial Pressure ≥ 65mmHg). Patients are included irrespective of indication for renal replacement therapy. Suspected or proven bacterial cause for vasoplegic shock is a contraindication. INTERVENTION AND COMPARATOR: Within 24 hours after meeting the inclusion criteria patients will be randomized to receive either standard of care or standard of care and additional "CytoSorb" therapy via a shaldon catheter for 3-7 days. Filter exchange is done every 24 hours. If patients receive antibiotics, an additional dose of antibiotics is administered after each change of "CytoSorb" filter in order to prevent underdosing due to "CytoSorb" treatment. MAIN OUTCOMES: Primary outcome is time to resolution of vasoplegic shock (defined as no need for vasopressors for at least 8 hours in order to sustain a MAP ≥ 65mmHg) in days. Secondary outcomes are 7 day mortality after fulfilling the inclusion criteria, mortality until hospital discharge, Interleukin-6 (IL-6) measurement on day 1 and 3, need for mechanical ventilation, duration of mechanical ventilation, duration of ICU-stay, catecholamine dose on day 1/2/3 after start of "CytoSorb" and acute kidney injury. RANDOMIZATION: An electronic randomization will be performed using the study software secuTrial® administered by the Clinical Study Center (CSC) of the Charité - Universitätsmedizin Berlin, Germany. Randomization is done in blocks by 4 stratified by including center. BLINDING (MASKING): The trial will be non-blinded for the clinicians and patients. The statistician will receive a blinded data set, so that all analyses will be conducted blinded. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): As this is a pilot study with the goal to examine the feasibility of the study design as well as the intervention effect, no formal sample size calculation was conducted. A total number of approximately 80-100 patients is planned (40-50 patients per group). Safety assessment is done after the inclusion of each 10 patients per randomization group. TRIAL STATUS: Please see the study protocol version from April 24 2020. Recruitment of patients is still pending. TRIAL REGISTRATION: The study was registered on April 27 2020 in the German Registry of Clinical Trials (DRKS) under the number DRKS00021447. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Control of neutrophil influx during peritonitis by transcriptional cross-regulation of chemokine CXCL1 by IL-17 and IFN-γ.

Neutrophil infiltration is a hallmark of peritoneal inflammation, but mechanisms regulating neutrophil recruitment in patients with peritoneal dialysis (PD)-related peritonitis are not fully defined. We examined 104 samples of PD effluent collected during acute peritonitis for correspondence between a broad range of soluble parameters and neutrophil counts. We observed an association between peritoneal IL-17 and neutrophil levels. This relationship was evident in effluent samples with low but not high IFN-γ levels, suggesting a differential effect of IFN-γ concentration on neutrophil infiltration. Surprisingly, there was no association of neutrophil numbers with the level of CXCL1, a key IL-17-induced neutrophil chemoattractant. We investigated therefore the production of CXCL1 by human peritoneal mesothelial cells (HPMCs) under in vitro conditions mimicking clinical peritonitis. Stimulation of HPMCs with IL-17 increased CXCL1 production through induction of transcription factor SP1 and activation of the SP1-binding region of the CXCL1 promoter. These effects were amplified by TNFα. In contrast, IFN-γ dose-dependently suppressed IL-17-induced SP1 activation and CXCL1 production through a transcriptional mechanism involving STAT1. The SP1-mediated induction of CXCL1 was also observed in HPMCs exposed to PD effluent collected during peritonitis and containing IL-17 and TNFα, but not IFN-γ. Supplementation of the effluent with IFN-γ led to a dose-dependent activation of STAT1 and a resultant inhibition of SP1-induced CXCL1 expression. Transmesothelial migration of neutrophils in vitro increased upon stimulation of HPMCs with IL-17 and was reduced by IFN-γ. In addition, HPMCs were capable of binding CXCL1 at their apical cell surface. These observations indicate that changes in relative peritoneal concentrations of IL-17 and IFN-γ can differently engage SP1-STAT1, impacting on mesothelial cell transcription of CXCL1, whose release and binding to HPMC surface may determine optimal neutrophil recruitment and retention during peritonitis. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Quality of design and reporting of animal research in peritoneal dialysis: A scoping review.

The concerns about reproducibility and validity of animal studies are partly related to poor experimental design and reporting. Here, we undertook a scoping review of the literature to determine the extent and quality of reporting of animal studies on peritoneal dialysis (PD). Online databases were searched to identify 567 relevant original articles published between 1979 and 2018. These were analyzed with respect to bibliographic parameters and general aspects of animal experimentation. A subgroup of 120 studies was analyzed in detail in terms of the impact on the reporting quality of the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines for animal studies. The number of animal studies on PD increased continuously over the years with a thematic shift toward long-term preservation of the peritoneum as a dialyzing organ. There were significant deficiencies in research design with the lack of sample size estimation, randomization, and blinding being the commonest shortcomings. The description of animal numbers, housing conditions, use of medication, and statistical analysis was incomplete. The introduction in 2010 of the ARRIVE guidelines produced very little improvement in the completeness of reporting regardless of journal impact factor. The animal studies on PD suffer from deficits in experimental protocols and transparent reporting. These drawbacks need to be corrected to ensure high-quality and much-needed animal research in PD.

Elimination of glutamate using CRRT for 72 h in patients with post-cardiac arrest syndrome: A randomized clinical pilot trial.

AIM: Glutamine and glutamate are major mediators of secondary brain cell death during post-cardiac arrest syndrome. As there is an equilibrium between brain tissue and plasma concentrations of glutamine and glutamate, their elimination from systemic circulation by extracorporeal blood purification may ultimately lead to reduced secondary cell death in the brain. We hypothesized that systemic glutamine and glutamate can be significantly reduced by continuous venovenous hemodiafiltration (CVVHDF). METHODS: This was a prospective, randomized clinical trial in post cardiac-arrest survivors evaluating standard of care or additional CVVHDF over 72 h immediately after admission. Glutamine and glutamate plasma concentrations were analyzed at eight time points in both groups. Primary endpoint was reduction of glutamine and glutamate plasma concentrations. The trial has been registered at clinical trial.gov (NCT02963298). RESULTS: In total, 41 patients were randomized over a period of 12 months (control n = 21, CVVHDF n = 20). The primary aim reduction of glutamine and glutamate plasma concentrations by CVVHDF, was not achieved; both groups-maintained concentrations within a normal range over the study period (glutamate: 4.7-11.1 mg/dL; glutamine: 0.2-3.7 mg/dL). However, post-filter concentrations of glutamine and glutamate in CRRT patients were significantly decreased as compared to pre-filter concentrations (glutamate: pre-filter median 8.85 mg/dL IQR 7.1-9.6; post-filter 0.95 mg/dL IQR 0.5-2; p < 0.001; glutamine: pre-filter 0.7 mg/dL IQR 0.6-1; post-filter 0.2 mg/dL IQR 0-0.2; p < 0.001). CONCLUSION: In this trial, CVVHDF was not able to statistically significantly lower systemic plasma glutamine and glutamate levels. Post-cardiac arrest patients had plasma glutamine and glutamate levels within the normal range.

Epithelial-to-Mesenchymal Transition and Migration of Human Peritoneal Mesothelial Cells Undergoing Senescence.

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) of human peritoneal mesothelial cells (HPMCs) contributes to fibrotic thickening of the peritoneum that develops in patients on peritoneal dialysis (PD). The process is thought to be largely mediated by transforming growth factor-beta (TGF-ß). As TGF-ß has also been implicated in senescence of HPMCs, we have performed an exploratory study to examine if senescent HPMCs can undergo EMT. METHODS: Omentum-derived HPMCs were rendered senescent by repeated passages in culture. Features of EMT were assessed by immunostaining and quantitative polymerase chain reaction (qPCR) at various stages of the HPMC lifespan and after treatment with or without TGF-ß. The motility of HPMCs was assessed in a scratch wound migration assay. RESULTS: Replicative senescence of HPMCs was associated with a gradual increase in the constitutive expression of EMT markers, including increased production of extracellular matrix proteins. However, senescent HPMCs also retained epithelial cell features such as cytokeratin, calretinin, and E-cadherin and showed decreased, rather than increased, motility. In contrast, exposure to TGF-ß resulted in an up-regulation of mesenchymal markers and down-regulation of epithelial markers. Such effects of TGF-ß occurred both in young and senescent cells, although they were less pronounced in senescence. CONCLUSIONS: Senescence of HPMCs is associated with spontaneous development of several EMT features. At the same time, senescent HPMCs preserve epithelial cell-like characteristics and are less prone to develop a full EMT phenotype in response to TGF-ß. These observations may support the concept of cellular senescence being antagonistically pleiotropic with regard to EMT.

IL-17 in Peritoneal Dialysis-Associated Inflammation and Angiogenesis: Conclusions and Perspectives.

Long-term peritoneal dialysis (PD) is associated with peritoneal membrane remodeling. This includes changes in peritoneal vasculature, which may ultimately lead to inadequate solute and water removal and treatment failure. The potential cause of such alterations is chronic inflammation induced by repeated episodes of infectious peritonitis and/or exposure to bioincompatible PD fluids. While these factors may jeopardize the peritoneal membrane integrity, it is not clear why adverse peritoneal remodeling develops only in some PD patients. Increasing evidence points to the differences that occur between patients in response to the same invading microorganism and/or the differences in the course of inflammatory reaction triggered by different species. Such differences may be related to the involvement of different inflammatory mediators. Here, we discuss the potential role of IL-17 in these processes with emphasis on its impact on peritoneal mesothelial cells and peritoneal vascularity.

Peritoneal dialysis catheter leakage following intermittent vacuum therapy.

Peripheral arterial disease and diabetic foot syndrome are common comorbidities in dialysis patients. These conditions are treated with intermittent vacuum therapy in order to increase angiogenesis and perfusion. Some devices encase the lower extremities up to the abdomen. Here we report the case of a patient who had performed peritoneal dialysis for 2 years without complications. Following postoperative intermittent vacuum therapy, he presented with extensive catheter leakage. Ultimately the patient had to be switched to haemodialysis and the catheter had to be removed. This case exemplifies that peritoneal dialysis patients have a substantial risk for noninfectious catheter-related complications using vacuum therapy.