Immunomodulatory effect of hemodialysis extracorporeal treatment and comparative study of different high flux membranes

Backgroud. L'infiammazione cronica, fattore di rischio cardiovascolare, dipende da fattori non correlati alla dialisi e correlati, come la biocompatibilità della membrana e la permeabilità alle medie molecole (citochine infiammatorie). L'uremia determina una disfunzione immunitaria con tendenza alle infezioni. Questo studio valuta l'effetto immunomodulatorio della singola sessione di dialisi e confronta tre diverse membrane ad alto flusso. Metodi. Sono stati arruolati 35 pazienti in emodialisi cronica trisettimanale e 10 volontari sani. Per due settimane i gruppi A e C sono stati sottoposti a emodialisi con Filtryzer-BGU 1.6 e THERANOVA, il gruppo B a emofiltrazione con HFR17. Cellule mononucleate del sangue periferico (PBMC) sono state raccolte all'inizio (T0) e alla fine (T1) della 5a sessione e all'inizio della 6a (T2) per eseguire citofluorimetria e saggi di proliferazione cellulare e apoptosi. Risultati. Nei pazienti in dialisi i linfociti CD3+, B e T si riducono, per aumento dell'apoptosi. NK, CD8+CD57+ senescenti e Th17 aumentano. Durante la seduta CD3+ subiscono un calo significativo secondario all'apoptosi, per incrementare, non significativamente, in T2. In T1 CD4+ aumentano per proliferazione, così come il rapporto Treg/Th17 e cala alla sessione successiva. CD8+ diminuiscono in T1 e T2, contestualmente ad una riduzione della produzione di IFN-γ. Il rapporto CD4+/CD8+ aumenta in T1 per diminuire nell'intervallo interdialitico. CD8+CD57+ e la produzione di IFN-γ diminuiscono durante il trattamento. NK e monociti diminuiscono durante la sessione per aumentare nell'intervallo interdialitico. Confrontando i filtri non sono state registrate variazioni statisticamente significative. Conclusioni. L’emodialisi rappresenta un trigger infiammatorio in un sistema immunitario iperattivo e disfunzionale, come testimoniato dall’incremento di sottopopolazioni linfocitarie ad elevato potenziale citotossico ed infiammatorio. Il singolo trattamento tende a correggere questo stato rimovendo mediatori dell’infiammazione, con progressivo ripristino delle condizioni basali nel corso dell’intervallo interdialitico. L’impiego di diverse membrane non influenza le sottopopolazioni linfocitarie né dal punto di visa numerico né funzionale.Introduction. Chronic inflammation is a cardiovascular risk factor observed in hemodialysis patients. It depends both on dialysis-unrelated and related factors, as membrane biocompatibility and permeability to middle molecule, including inflammation cytokines. On the other hand, uremia is associated with immune dysfunction and high prevalence of infections. This study focuses on immunomodulatory effect of single dialysis session and compares three different high flux membranes. Methods. 35 maintenance hemodialysis three times per-week patients and 10 healthy volunteers were enrolled. For two weeks group A and C underwent hemodialysis with Filtryzer BGU 1.6 and THERANOVA respectively, group B hemofiltration with HFR17. Peripherical blood mononuclear cells (PBMC) were collected at the beginning (T0) and the end (T1) of the 5th session and starting the 6th session (T2). Previous sessions allowed wash-out from usual treatment. Cytofluorimetry, cellular proliferation and apoptosis essay were performed. Results. CD3+, B and T lymphocytes reduce, according to increased apoptosis in dialysis patients, compared to healthy volunteers. NK, senescence CD8+ CD57+ and Th17 increase. During session CD3+ suffer a significant drop secondary to apoptosis, to rise again, not significantly, on T2. On T1 CD4+ increase due to proliferation, as well as Treg/Th17 ratio and drop on next session. CD8+ decrease on T1 and T2 according to IFN-γ production. CD4+/CD8+ ratio is increased in T1 to decrease in interdialytic interval. CD8+ CD57+ and IFN-γ production drop during treatment, persisting on 6th dialysis. NK and monocytes decrease during session to rise in interdialytic interval. Comparing the three different dialyzer no statistically significant variations were recorded. Conclusions. Replacement therapy represents an acute inflammatory trigger in terminal uremia hyperactive and dysfunctional immune system, as evidenced by the increase in cytotoxic lymphocyte subpopulations compared to healthy population. Single dialysis session attempts to correct dysfunctional inflammatory state, removing mediators, with restoration of basal conditions in interdialytic interval

Impact of Single Hemodialysis Treatment on immune Cell Subpopulations

: Hemodialysis (HD) is known to trigger a chronic inflammatory status, affecting the innate and acquired immune response. This study was aimed at a comparative analysis of immune cell subsets, proliferation, and apoptosis in subjects receiving chronic HD treatment with respect to a healthy control. Regardless of the dialysis filter used, we observed a reshaping of the acquired immune component both with respect to healthy patients and between the various sessions of dialysis treatment, with an impairment of CD3 cells, along with an increase in CD4 and CD8 cell populations producing pro-inflammatory factors such as IL-17 and IFN-gamma. The population of B cells, monocytes and NK cells were not impaired by the dialysis procedure. These results confirmed the high impact of the HD treatment on the patient's immune system, underlying the imbalance of T cell counterparts

Plasmapheresis in the Intensive Care: The Word Goes to the Nephrologist

Abstract. Nowadays, apheresis treatments include a wide variety of extracorporeal treatments that are advisable in different pathological conditions, ranging from immunological diseases to sepsis, from liver failure to toxic pathologies. Since treatments can be scheduled and repeated at specific intervals, they are usually entrusted to the Transfusion Services. However, in the event of emergency conditions with a quoad vitam prognosis, these special treatments should be performed also in the Intensive Care Units. Nephrologists dispose of the complete know-how to directly perform apheresis in the critical area, where patients with intoxications, poisoning, acute hepatitis, and any other extremely severe clinical status need intensive support to their vital functions (pulmonary, cardiac, neurologic, etc.) An urgent plasmapheresis can be defined as an apheretic treatment that should be started as early as possible, and never more than 24-36 hours after diagnosis, in case of a life-threatening situation and no other valid alternative available. Some neurologic diseases, intoxications, and hemolysis are recognized situations for which plasmapheresis is advisable in association with the pharmacological therapy. Today, the equipment used for the extracorporeal treatments for acute renal failure can also be used for the classical plasma-exchange treatments. The substantial technological familiarity and expertise of nephrologists and nurses make apheresis treatments safe. Moreover, thanks to technological progress, new instruments are now available to treat plasma onto resins rather than replacing it. Such treatments are now applied, among others, especially in sepsis and liver failure, and should be part of the professional training of the nephrological staff working in the critical area

Coupled Plasma Filtration Adsorption Application for Liver and Thyroid Toxins

none6noCoupled plasma filtration and adsorption (CPFA) is a detoxification system that combines a plasma adsorption circuit and a continuous renal replacement therapy circuit. Its main application is for sepsis and septic shock with or without acute renal failure. Several recent studies have suggested that CPFA can reduce the mortality when the volume of plasma absorbed on the styrenic resin is at least >0.18 L/kg/day. At present, new applications for CPFA are under investigation, also in patients without significant kidney failure. We report here a successful case of CPFA use during acute liver failure, with a complete recovery of liver function in a patient after severe cholangitis and relapsing hemolytic anemia. The resin enabled the removal of bilirubin and protein-bound toxins, while the hemofilter removed the hydrophilic toxins such as ammonia and non-protein-bound toxins as free bilirubin. We also describe a second case of CPFA application during thyrotoxicosis to achieve free triiodothyronine (FT3) and free thyroxin (FT4) adsorptions. The CPFA efficacy seems to exceed that obtained by plasma exchange (PEX) as to FT3 and FT4 adsorptions. The resin allowed the adsorption of FT3 and FT4. The role of the hemofilter is to enhance the hemodynamic tolerance of the extracorporeal treatment and remove water-soluble toxins. The reduced duration of CPFA treatments, in case of normal renal function, is confirmed by the assessment of the resin cartridge saturation. Thus, multipurpose CPFA can play a role in the case of resistance to current medical therapy or as a bridge to liver transplantation or thyroidectomy.mixedmixedDonati, Gabriele; Capelli, Irene; Chiocchini, Anna Laura Croci; Natali, Nicolò; Scrivo, Anna; La Manna, GaetanoDonati, Gabriele; Capelli, Irene; Chiocchini, Anna Laura Croci; Natali, Nicolò; Scrivo, Anna; La Manna, Gaetan

SP477HEPATIC REGENERATION WITH COUPLED PLASMAFILTRATION AND ADSORPTION FOR LIVER EXTRACORPOREAL DETOXIFICATION (HERCOLE STUDY)

n/

Rituximab as First-Line Therapy in Severe Lupus Erythematosus with Neuropsychiatric and Renal Involvement: A Case-Report and Review of the Literature

Neuropsychiatric and renal involvement are common in systemic lupus erythematosus with negative impact on patient survival. Glucocorticoids, antiproliferative and cytotoxic agents represent first-line therapies, but are often ineffective and are burdened by significant toxicities. Despite the negative results of two randomized controlled trials, rituximab is still widely used as second- or third-line therapy in similar cases. No case has been reported so far where rituximab has been used as first-line therapy. We report the case of a 60-year-old cCaucasian woman with concurrent neuropsychiatric and renal lupus erythematous treated with one cycle of rituximab therapy at disease onset. Treatment was well tolerated and at 24 months the patient is in complete remission and free of immunosuppression. To the best of our knowledge, this is the first case of neuropsychiatric and renal lupus erythematosus successfully treated with rituximab as first-line therapy

HEPATIC REGENERATION WITH COUPLED PLASMAFILTRATION AND ADSORPTION FOR LIVER EXTRACORPOREAL DETOXIFICATION (HERCOLE STUDY)

INTRODUCTION AND AIMS: CPFA (Coupled plasma filtration and adsorption) is currently used in the treatment of severe sepsis with the intention of removing the proinflammatory mediators from the systemic circulation. Some evidence exist about the bilirubin adsorbing ability of the neutral styrenic resin which is part of the extracorporeal circuit of CPFA. The aim of this study is to assess efficacy and safety of CPFA in extracorporeal detoxification of liver toxins in patients affected by acute or acute-onchronic liver failure (Figure 1). METHODS: Twelve patients (age 23 - 73 years) with acute (n \ubc 3) or acute-on-chronic (n \ubc 9) liver failure were enrolled. A total of 31 CPFA treatments were carried out. Each CPFA treatment lasted 6 hours. Unfractionated heparin was used as anticoagulation of the extracorporeal circuit in 19 CPFA sessions; citrate anticoagulation with the concomitant infusion of calcium chloride in 12 CPFA sessions. The number of treatment for each patient was established on his/her clinical status. The reduction ratios per session of bilirubin and bile acids were considered. Hemoglobin, platelets, white blood cells, coagulation tests, urea, creatinine and electrolytes were also checked on starting CPFA and at the end of CPFA, as biocompatibility measures. RESULTS: All sessions were well tolerated by the patients. Alcohol was the most common etiology of the liver injury (n \ubc 9), 1 patient was affected by acute cholangitis and Fisher-Evans syndrome, 1 had a viral etiology, and 1 patient had a postoperative jaundice. Median reduction rate per session for total bilirubin was 28.8% (range 2.2 - 40.5); for direct bilirubin was 32.7 (range 8.3 - 48.9); for indirect bilirubin was 29.5% (range 6.5 - 65.4); for bile acids was 28.9% (16.7 - 59.7); for lactic acid was 30% (range -57.2%- 55.6%). In 10 out of 12 patients was observed a recovery of liver function. At one year of follow-up 2 patients died during the hospitalization; 6 patients are followed like outpatients, recovered their basal liver function and 1 of them is no more in the waiting list for the transplant. As to the remaining 4 patients who have not yet completed the one year follow-up, 2 out of 4 are still alive after a 6-month follow-up and recovered their basal liver function, 1 patient underwent a successful liver transplantation, the last patient is still alive after a 3-month follow up. CONCLUSIONS: Although CPFA is a non-standardized technique for the liver failure, its use in patients with acute or acute-on-chronic liver failure has shown favorable effects on safety and efficacy in terms of detoxification. Thus it is considerable a \u201cbridge technique\u201d toward the liver transplant and the recovery of basal liver function

An in vitro model of renal inflammation after ischemic oxidative stress injury: nephroprotective effects of a hyaluronan ester with butyric acid on mesangial cells

Background: Acute kidney injury, known as a major trigger for organ fibrosis and independent predictor of chronic kidney disease, is characterized by mesangial cell proliferation, inflammation and unbalance between biosynthesis and degradation of extracellular matrix. Therapeutic approaches targeting the inhibition of mesangial cell proliferation and matrix expansion may represent a promising opportunity for the treatment of kidney injury. An ester of hyaluronic acid and butyric acid (HB) has shown vasculogenic and regenerative properties in renal ischemic-damaged tissues, resulting in enhanced function recovery and minor degree of inflammation in vivo. This study evaluated the effect of HB treatment in mesangial cell cultures exposed to H2O2-induced oxidative stress. Materials and methods: Lactate dehydrogenase release and caspase-3 activation were measured using mesangial cells prepared from rat kidneys to assess necrosis and apoptosis. Akt and p38 phosphorylation was analyzed to identify the possible mechanism underlying cell response to HB treatment. The relative expressions of matrix metallopeptidase 9 (MPP-9) and collagen type 1 alpha genes were also analyzed by quantitative real-time polymerase chain reaction. Cell proliferation rate and viability were measured using thiazolyl blue assay and flow cytometry analysis of cell cycle with propidium iodide. Results: HB treatment promoted apoptosis of mesangial cells after H2O2-induced damage, decreased cellular proliferation and activated p38 pathway, increasing expression of its target gene MPP-9. Conclusion: This in vitro model shows that HB treatment seems to redirect mesangial cells toward apoptosis after oxidative damage and to reduce cell proliferation through p38 MAPK pathway activation and upregulation of MPP-9 gene expression involved in mesangial matrix remodeling

Vitamin D and the Kidney: Two Players, One Console

Vitamin D belongs to the group of liposoluble steroids mainly involved in bone metabolism by modulating calcium and phosphorus absorption or reabsorption at various levels, as well as parathyroid hormone production. Recent evidence has shown the extra-bone effects of vitamin D, including glucose homeostasis, cardiovascular protection, and anti-inflammatory and antiproliferative effects. This narrative review provides an overall view of vitamin D’s role in different settings, with a special focus on chronic kidney disease and kidney transplant