Yet another in vitro evidence that natural compounds introduced by diet have anti-amyloidogenic activities and can counteract neurodegenerative disease depending on aging.

A major issue in Alzheimer's disease (AD) research is to find some new therapeutic drug which decrease Amyloid-beta (Aß) aggregation. From a therapeutic point of view the major question is whether pharmacological inhibition of inflammation pathways will be able to safely reverse or slow the course of disease. Natural compounds are capable of binding to different targets implicated in AD and exert neuroprotective effects. Aim of this study was to evaluate the in vitro inhibition of Aß1-42 fibrillogenesis in presence of Gallic acid, Rutin, Melatonin and ProvinolsTM . We performed the analysis with Transmission and Scanning Electron Microscopy, and with X-ray microanalysis. Samples treated with Rutin, that arises from phenylalanine via the phenylpropanoid pathway, show the best effective result obtained because a significantly fibril inhibition activity is detectable compared to the other compounds. Melatonin shows a better inhibitory activity than ProvinolsTM and Gallic acid at the considered concentrations.

Induction of Vesicular Trafficking and JNK-Mediated Apoptotic Signaling in Mononuclear Leukocytes Marks the Immuno-Proteostasis Response to Uremic Proteins.

INTRODUCTION: Uremic retention solutes have been alleged to induce the apoptotic program of different cell types, including peripheral blood mononuclear leukocytes (PBL), which may contribute to uremic leukopenia and immune dysfunction. METHODS: The molecular effects of these solutes were investigated in uremic PBL (u-PBL) and mononuclear cell lines (THP-1 and K562) exposed to the high molecular weight fraction of uremic plasma (u-HMW) prepared by in vitro ultrafiltration with 50 kDa cut-off microconcentrators. RESULTS: u-PBL show reduced cell viability and increased apoptotic death compared to healthy control PBL (c-PBL). u-HMW induce apoptosis both in u-PBL and c-PBL, as well as in mononuclear cell lines, also stimulating cellular H2O2 formation and secretion, IRE1-α-mediated endoplasmic reticulum stress signaling, and JNK/cJun pathway activation. Also, u-HMW induce autophagy in THP-1 monocytes. u-PBL were characterized by the presence in their cellular proteome of the main proteins and carbonylation targets of u-HMW, namely albumin, transferrin, and fibrinogen, and by the increased expression of receptor for advanced glycation end-products, a scavenger receptor with promiscuous ligand binding properties involved in leukocyte activation and endocytosis. CONCLUSIONS: Large uremic solutes induce abnormal endocytosis and terminal alteration of cellular proteostasis mechanisms in PBL, including UPR/ER stress response and autophagy, ultimately activating the JNK-mediated apoptotic signaling of these cells. These findings describe the suicidal role of immune cells in facing systemic proteostasis alterations of kidney disease patients, a process that we define as the immuno-proteostasis response of uremia.

ELISPOT assays with pp65 peptides or whole HCMV antigen are reliable predictors of immune control of HCMV infection in seropositive kidney transplant recipients.

Human cytomegalovirus (HCMV) infection represents a major complication for solid organ transplant recipients. The aim of this study was to verify if the measurement of HCMV-specific T-cells could help to identify patients protected against HCMV disease cytokine flow cytometry using infected dendritic cells as stimulus (CFC-iDC, which discriminates between CD4+ and CD8+ T cells), and ELISPOT, using infected cell lysate (ELISPOT-iCL) or pp65 (ELISPOT-pp65) as stimulus, were adopted. Among the 47 kidney transplant recipients (KTR) enrolled, 29 had a self-resolving HCMV infection (Controllers) and 18 required antiviral treatment (Non-Controllers). HCMV-specific T-cell frequency at the peak of HCMV infection identified Controllers and Non-Controllers, although the diagnostic performance of CD8+ CFC-iDC (area under the curve [AUC] of the receiver-operator characteristic curve: 0.65) was lower than that of CD4+ CFC-iDC (AUC: 0.83), ELISPOT-iCL (AUC: 0.83) and ELISPOT-pp65 (AUC: 0.80). CFC-iDC detected a protective immune reconstitution significantly earlier (median time: 38 days) than ELISPOT-iCL and ELISPOT-pp65 (median time: 126 and 133 days, respectively). Time to protective immune reconstitution in Non-Controllers was significantly longer than in Controllers with the ELISPOT and the CD4+ CFC-iDC assays, but not with CD8+ CFC-iDC. The majority of patients did not require antiviral treatment after protective immune reconstitution, with the exception of five patients according to CFC-iDC assay, one patient according to ELISPOT-iCL assay and three patients according to ELISPOT-pp65 assay. Monitoring the HCMV-specific immunological reconstitution with is effective in discriminating KTR at risk of or protected from HCMV disease and the ELISPOT assays are suitable for implementation in the clinical setting.

Safety and Effectiveness of Veno-Venous Extracorporeal Membrane Oxygenation Combined With Continuous Renal Replacement Therapy.

Patients receiving extracorporeal membrane oxygenation (ECMO) often suffer from acute kidney injury (AKI), requiring continuous renal replacement therapy (CRRT). In our clinical practice, we connected the inlet line of a CRRT machine to the postoxygenator Luer port and the outlet line to the inlet Luer port of the oxygenator. In this case series, we analyzed the interaction between the two machines. Between December 31, 2017, and December 31, 2019, we enrolled 15 patients from the ICU of the San Matteo Hospital, Pavia, Italy. All of them suffered from severe acute respiratory distress syndrome and AKI stage 3. We analyzed 570 hours of CRRT combined with venovenous ECMO and collected 261,751 CRRT data. No discontinuation of CRRT occurred before 48 hours. Most of the alarms occurred within 24 hours of the connection: 22/10,831 (0.2%) showed an outranged inlet pressure, 11/10831 (0.11%) showed an outranged transmembrane pressure, 14/10,831 (0.13%) showed an outranged inlet pressure, and 138/10,831 (1.27%) an outranged effluent pressure. The rate per minute set for the ECMO circuit was correlated with the inlet (ß = 5.38; CI, 95% 1.42-9.35; p = 0.008), transmembrane (ß = 4.6; CI, 95% 1.97-7.24; p = 0.001), effluent (ß = 3.02; CI, 95% 1.15-4.90; p = 0.002), and outlet pressures (ß = 597; CI, 95% 2.31-9.63; p = 0.001) of the CRRT circuit. We reported that our configuration could be safe and effective, however well-designed studies would be beneficial for determining the potential risks and benefits.

Impediments to Heart Transplantation in Adults With MELASMT-TL1:m.3243A>G Cardiomyopathy.

BACKGROUND: The heart is commonly involved in maternally inherited mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome caused by the MT-TL1 m.3243A>G mutation of the mitochondrial DNA. Heart transplantation (HTx) is controversial and has rarely been performed with conflicting results. OBJECTIVES: We analyzed factors preventing HTx in consecutive adult patients with MELASMT-TL1:m.3243A>G cardiomyopathy diagnosed and followed during the last 23 years in our HTx referral center. METHODS: The series consists of 14 unrelated adult probands who were referred for evaluation of cardiomyopathy from 1998 to 2021. None had a suspected diagnosis of MELAS before referral. All patients underwent clinical and genetic visit and counseling, mitochondrial DNA sequencing, cardiovascular investigation (including right heart catheterization and endomyocardial biopsy in 10), multidisciplinary assessment, and biochemical tests. Family screening identified 2 affected relatives. RESULTS: The cardiac phenotype was characterized by hypertrophic, concentric, nonobstructive cardiomyopathy that often evolved into a dilated cardiomyopathy-like phenotype. Of the 14 probands, 7 were potential candidates for HTx, 2 for heart and kidney Tx, and 1 was on the active HTx list for 3 years. None of the 10 probands underwent HTx. One is currently being evaluated for HTx. All had diabetes, hearing loss, and myopathy, and 10 had chronic kidney disease and progressive encephalomyopathy. During follow-up, 10 died from heart failure associated with multiorgan failure within 5 years of the genetic diagnosis. CONCLUSIONS: High risk of stroke-like episodes, chronic kidney disease, and wasting myopathy in MELASMT-TL1:m.3243A>G patients prevents activation of plans for HTx. As a result, the management of their cardiomyopathy in this syndromic context remains an unmet clinical need.

CD73-Adenosinergic Axis Mediates the Protective Effect of Extracellular Vesicles Derived from Mesenchymal Stromal Cells on Ischemic Renal Damage in a Rat Model of Donation after Circulatory Death.

We propose a new organ-conditioning strategy based on mesenchymal stromal cell (MSCs)/extracellular vesicle (EVs) delivery during hypothermic perfusion. MSCs/EVs marker CD73 is present on renal proximal tubular cells, and it protects against renal ischemia-reperfusion injury by converting adenosine monophosphate into adenosine (ADO). In this study, after checking if CD73-silenced EVs (EVsi) would impact in vitro tubular-cell proliferation, we perfused kidneys of a rat model of donation after circulatory death, with Belzer solution (BS) alone, BS supplemented with MSCs, EVs, or EVsi. The ADO and ATP levels were measured in the effluents and tissues. Global renal ischemic damage score (GRS), and tubular cell proliferation index (IPT) were evaluated in the tissue. EVsi did not induce cell proliferation in vitro. Ex vivo kidneys perfused with BS or BS + EVsi showed the worst GRS and higher effluent ADO levels than the MSC- and EV-perfused kidneys. In the EV-perfused kidneys, the tissue and effluent ATP levels and IPT were the highest, but not if CD73 was silenced. Tissue ATP content was positively correlated with tissue ADO content and negatively correlated with effluent ADO level in all groups. In conclusion, kidney conditioning with EVs protects against ischemic damage by activating the CD73/ADO system.

SARS-CoV-2-specific IgG and NCP in vulnerable patients without symptoms.

Patients with severe COVID-19 both seroconvert earlier and develop higher concentrations of SARS- CoV-2-specific IgG than patients with mild symptoms. In this retrospective study we considered different categories of patients defined as "vulnerable" because affected by other pathologies, such as patients with genetic and cardiovascular diseases; patients with autoimmune dermatological dis- ease; kidney and lung transplant patients, and pregnant women because the prevalence of Covid-19 infection during pregnancy is not known. This study was performed at IRCCS San Matteo Hospital in Pavia, North Italy, a zone considered at high risk during the COVID-19 pandemic from June to December 2020. None of the positive screened patients had symptoms of COVID-19 infection at the time of inclusion in this study.

Liposome Formulation and In Vitro Testing in Non-Physiological Conditions Addressed to Ex Vivo Kidney Perfusion.

This work focuses on formulating liposomes to be used in isolated kidney dynamic machine perfusion in hypothermic conditions as drug delivery systems to improve preservation of transplantable organs. The need mainly arises from use of kidneys from marginal donors for transplantation that are more exposed to ischemic/reperfusion injury compared to those from standard donors. Two liposome preparation techniques, thin film hydration and microfluidic techniques, are explored for formulating liposomes loaded with two model proteins, myoglobin and bovine serum albumin. The protein-loaded liposomes are characterized for their size by DLS and morphology by TEM. Protein releases from the liposomes are tested in PERF-GEN perfusion fluid, 4 °C, and compared to the in vitro protein release in PBS, 37 °C. Fluorescent liposome uptake is analyzed by fluorescent microscope in vitro on epithelial tubular renal cell cultures and ex vivo on isolated pig kidney in hypothermic perfusion conditions. The results show that microfluidics are a superior technique for obtaining reproducible spherical liposomes with suitable size below 200 nm. Protein encapsulation efficiency is affected by its molecular weight and isoelectric point. Lowering incubation temperature slows down the proteins release; the perfusion fluid significantly affects the release of proteins sensitive to ionic media (such as BSA). Liposomes are taken up by epithelial tubular renal cells in two hours' incubation time.

Effect of a Third Dose of SARS-CoV-2 mRNA BNT162b2 Vaccine on Humoral and Cellular Responses and Serum Anti-HLA Antibodies in Kidney Transplant Recipients.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has severely impacted on public health, mainly on immunosuppressed patients, including solid organ transplant recipients. Vaccination represents a valuable tool for the prevention of severe SARS-CoV-2 infection, and the immunogenicity of mRNA vaccines has been evaluated in transplanted patients. In this study, we investigated the role of a third dose of the BNT162b2 vaccine in a cohort of kidney transplant recipients, analyzing both humoral and cell-mediated responses. We observed an increased immune response after the third dose of the vaccine, especially in terms of Spike-specific T cell response. The level of seroconversion remained lower than 50% even after the administration of the third dose. Mycophenolate treatment, steroid administration and age seemed to be associated with a poor immune response. In our cohort, 11/45 patients experienced a SARS-CoV-2 infection after the third vaccine dose. HLA antibodies appearance was recorded in 7 out 45 (15.5%) patients, but none of the patients developed acute renal rejection. Further studies for the evaluation of long-term immune responses are still ongoing, and the impact of a fourth dose of the vaccine will be evaluated.

Early remdesivir to prevent severe COVID-19 in recipients of solid organ transplant: a real-life study from Northern Italy.

OBJECTIVES: The effectiveness of a 3-day course of remdesivir to prevent severe disease in patients with COVID-19 who received solid organ transplant (SOT) is unknown. We wanted to study the efficacy of this therapeutic option in patients with COVID-19 who received SOT in preventing both hospitalizations for outpatients and clinical worsening due to COVID-19 for those already hospitalized for other reasons. METHODS: This is a single-center, retrospective, observational study conducted in the Fondazione IRCSS Policlinico San Matteo of Pavia, Northern Italy. We extracted all the data of patients with COVID-19 receiving SOT who received and did not receive pre-emptive remdesivir between December 23, 2021, and February 26, 2022. We used a Cox proportional hazard model to assess whether receiving pre-emptive remdesivir was associated with lower rates of hospitalization. RESULTS: A total of 24 patients who received SOT were identified. Among these, seven patients (29, 1%) received pre-emptive remdesivir, whereas 17 (70, 9%) patients did not. Receiving remdesivir significantly reduced the hospitalization rate in outpatients who received SOT and the clinical worsening of the condition of already hospitalized patients who received SOT (hazard ratio 0.05; confidence interval [0.00-0.65], P-value = 0.01). CONCLUSION: In our cohort of patients infected with SARS-CoV-2 who received SOT, pre-emptive remdesivir was effective in reducing the hospitalization rate due to COVID-19 and in preventing the clinical worsening of the condition of patients who received SOT who were hospitalized for reasons other than COVID-19.

Extracellular Vesicles Derived from Mesenchymal Stromal Cells Delivered during Hypothermic Oxygenated Machine Perfusion Repair Ischemic/Reperfusion Damage of Kidneys from Extended Criteria Donors.

The poor availability of kidney for transplantation has led to a search for new strategies to increase the donor pool. The main option is the use of organs from extended criteria donors. We evaluated the effects of hypothermic oxygenated perfusion (HOPE) with and without extracellular vesicles (EV) derived from mesenchymal stromal cells on ischemic/reperfusion injury of marginal kidneys unsuitable for transplantation. For normothermic reperfusion (NR), we used artificial blood as a substitute for red blood cells. We evaluated the global renal ischemic dam-age score (GRS), analyzed the renal ultrastructure (RU), cytochrome c oxidase (COX) IV-1 (a mitochondrial distress marker), and caspase-3 renal expression, the tubular cell proliferation index, hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) tissue levels, and effluent lactate and glucose levels. HOPE+EV kidneys had lower GRS and better RU, higher COX IV-1 expression and HGF and VEGF levels and lower caspase-3 expression than HOPE kidneys. During NR, HOPE+EV renal effluent had lower lactate release and higher glucose levels than HOPE renal effluent, suggesting that the gluconeogenesis system in HOPE+EV group was pre-served. In conclusion, EV delivery during HOPE can be considered a new organ preservation strategy for increasing the donor pool and improving transplant outcome.

Renal Outcomes of Dialysis-Dependent Acute Kidney Injury in Noncritically Ill Patients: A Retrospective Study.

INTRODUCTION: Acute kidney injury (AKI) is a common complication among hospitalized patients, potentially affecting short- and long-term clinical outcomes. In this retrospective study, we evaluated renal outcomes in noncritically ill patients who required acute hemodialysis (HD) because of an AKI episode occurring during hospitalization. METHODS: Sixty-three hemodynamically stable patients with AKI undergoing acute intermittent HD were included. Kidney function was evaluated at baseline control (pre-AKI), at AKI diagnosis and during the follow-up. According to serum creatinine and the estimated glomerular filtration rate (eGFR), we defined three clinical conditions: renal recovery, different stages of acute kidney disease (AKD), and chronic kidney disease (CKD). RESULTS: Among the 63 patients evaluated, 34 patients (54%) had a history of CKD. Six patients (10%) presented early full renal recovery. HD treatment was stopped in 38 patients (60%), while 25 patients (40%) required maintenance HD. Dialysis-independent patients presented lower comorbidity and higher baseline eGFR and delta creatinine, compared to dialysis-dependent patients. Baseline CKD, previous AKI episodes, and parenchymal causes of AKI were associated with a significant risk of dialysis dependence. At 1-month control, 15 patients (39%) presented AKD stage 0, 6 patients (16%) AKD stage 1, and 17 patients (44%) AKD stage 2-3. At 3-month control, 29 out of 38 patients recovering from AKI (76%) presented CKD. AKD stage was significantly correlated with the risk of CKD development, which, resulted higher in patients with lower baseline eGFR. CONCLUSIONS: AKI might represent a risk factor for the development of chronic kidney damage, even in noncritically ill patients.

The innate immune system in human kidney inflammaging.

Elderly individuals with chronic disorders tend to develop inflammaging, a condition associated with elevated levels of blood inflammatory markers, and increased susceptibility to chronic disease progression. Native and adaptive immunity are both involved in immune system senescence, kidney fibrosis and aging. The innate immune system is characterized by a limited number of receptors, constantly challenged by self and non-self stimuli. Circulating and kidney resident myeloid and lymphoid cells are all equipped with pattern recognition receptors (PRRs). Recent reports on PRRs show kidney overexpression of toll-like receptors (TLRs) in inflammaging autoimmune renal diseases, vasculitis, acute kidney injury and kidney transplant rejection. TLR upregulation leads to proinflammatory cytokine induction, fibrosis, and chronic kidney disease progression. TLR2 blockade in a murine model of renal ischemia reperfusion injury prevented the escape of natural killer cells and neutrophils by inflammaging kidney injury. Tumor necrosis factor-α blockade in endothelial cells with senescence-associated secretory phenotype significantly reduced interleukin-6 release. These findings should encourage experimental and translational clinical trials aimed at modulating renal inflammaging by native immunity blockade.

Immune Response to BNT162b2 in Solid Organ Transplant Recipients: Negative Impact of Mycophenolate and High Responsiveness of SARS-CoV-2 Recovered Subjects against Delta Variant.

The immunogenicity of severe acute respiratory syndrome 2 virus (SARS-CoV-2) vaccines in immunocompromised patients remains to be further explored. Here, we evaluated the immunogenicity elicited by complete vaccination with BNT162b2 vaccine in solid organ transplant recipients (SOTRs). A cohort of 110 SOTRs from Northern Italy were vaccinated with two doses of BNT162b2 mRNA vaccine and prospectively monitored at baseline and after 42 days. Both SARS-CoV-2 naïve and recovered subjects were included. Humoral response elicited by vaccination, including SARS-CoV-2 neutralizing antibodies (SARS-CoV-2 NT Abs), was evaluated; additionally, ex-vivo ELISpot assay was performed for the quantification of Spike-specific T-cell response. Results were compared with those obtained in a cohort of healthy subjects. In a subset of patients, humoral and T-cell responses against delta variant were also evaluated. Less than 20% of transplanted subjects developed a positive humoral and cell-mediated response after complete vaccination schedule. Overall, median levels of immune response elicited by vaccination were significantly lower with respect to controls in SARS-CoV-2 naïve transplant, but not in SARS-CoV-2 recovered transplanted patients. Additionally, a significant impairment of both humoral and cell-mediated response was observed in mycophenolate-treated patients. Positive delta-SARS-CoV-2 NT Abs levels were detected in almost all the SARS-CoV-2 recovered subjects but not in previously uninfected patients. Our study supports previous observations of a low level of seroconversion after vaccination in transplanted patients.

Kidney transplant rejection rate in screened patients for anti-SARS-CoV-2 antibodies, during COVID-19 pandemic in Northern Italy.

Coronavirus is a high-risk pathogen for kidney transplant recipients receiving immunosuppressive therapy; Coronavirus disease 2019 (COVID-19) is an infection causing severe acute respiratory syndrome (SARS-CoV2), and progressive withdrawal of immunosuppressive drugs has been suggested in transplanted patients. At IRCCS San Matteo Hospital in Pavia, Northern Italy, during the pandemic we performed a screening and all transplanted patients were evaluated for IgG anti SARS-CoV-2; 12 of 201 kidney transplant recipients (6%) screened for IgG anti SARS-CoV-2 (s) developed kidney transplant rejection; 10 (83%) were negative and 2 (17%) resulted positive for SARS-CoV-2 IgG, while among 189 patients without rejection, 162 (86%) resulted negative and 27 (14%) positive (P=0.69). COVID 19 course may be more severe in kidney transplant recipients but it does not significantly increase risk of kidney rejection.

Robust and Persistent B- and T-Cell Responses after COVID-19 in Immunocompetent and Solid Organ Transplant Recipient Patients.

The development and persistence of SARS-CoV-2-specific immune response in immunocompetent (IC) and immunocompromised patients is crucial for long-term protection. Immune response to SARS-CoV-2 infection was analysed in 57 IC and 15 solid organ transplanted (TX) patients. Antibody responses were determined by ELISA and neutralization assay. T-cell response was determined by stimulation with peptide pools of the Spike, Envelope, Membrane, and Nucleocapsid proteins with a 20-h Activation Induced Marker (AIM) and 7-day lymphoproliferative assays. Antibody response was detected at similar levels in IC and TX patients. Anti-Spike IgG, IgA and neutralizing antibodies persisted for at least one year, while anti-Nucleocapsid IgG declined earlier. Patients with pneumonia developed higher antibody levels than patients with mild symptoms. Similarly, both rapid and proliferative T-cell responses were detected within the first two months after infection at comparable levels in IC and TX patients, and were higher in patients with pneumonia. T-cell response persisted for at least one year in both IC and TX patients. Spike, Membrane, and Nucleocapsid proteins elicited the major CD4+ and CD8+ T-cell responses, whereas the T-cell response to Envelope protein was negligible. After SARS-CoV-2 infection, antibody and T-cell responses develop rapidly and persist over time in both immunocompetent and transplanted patients.

Characterization of Varicella-Zoster (VZV) Specific T Cell Response in Healthy Subjects and Transplanted Patients by Using Enzyme Linked Immunospot (ELISpot) Assays.

Solid organ transplant recipients, due to the administration of post-transplant immunosuppressive therapies, are at greater risk of viral reactivation episodes, mainly from herpes viruses, including varicella-zoster virus (VZV). The aim of this pilot study was to develop functional immunological assays (VZV-ELISpot) for the quantification and characterization of the VZV-specific effector-memory and central-memory responses in healthy subjects and transplanted patients. Glycoprotein gE and immediate-early 63 (IE-63) were used as antigens for in vitro stimulation. VZV-seropositive healthy subjects showed higher responses in respect to seronegative subjects. Even if differences were observed between VZV-seropositive healthy subjects and transplanted subjects at pre-transplant, the VZV-specific T-cell response was reduced at 60 days after transplant, mainly for the high level of immunosuppression. Phenotypical characterization revealed that response against VZV was mainly mediated by CD4 T cells. The results obtained in this study might be useful for the definition of personalized follow-up of the transplanted patients, providing useful information on the status of the patient potentially at risk of viral reactivation or other opportunistic infections.

Photopheresis Abates the Anti-HLA Antibody Titer and Renal Failure Progression in Chronic Antibody-Mediated Rejection.

OBJECTIVE: Chronic renal antibody-mediated rejection (ABMR) is a common cause of allograft failure, but an effective therapy is not available. Extracorporeal photopheresis (ECP) has been proven successful in chronic lung and heart rejection, and graft versus host disease. The aim of this study was to evaluate the effectiveness of ECP in chronic ABMR patients. PATIENTS AND METHODS: We investigated ECP treatment in 14 patients with biopsy-proven chronic ABMR and stage 2-3 chronic renal failure. The primary aim was to e valuate the eGFR lowering after 1 year of ECP therapy. The ECP responders (R) showed eGFR reduction greater than 20% vs the basal levels. We also evaluated the effectiveness of ECP on proteinuria, anti-HLA antibodies (HLAab), interleukin 6 (IL-6) serum levels, and CD3, CD4, CD8, CD19, NK, Treg and T helper 17 (Th17) circulating cells. RESULTS: Three patients dropped out of the study. The R patients were eight (72.7%) out of the 11 remaining patients. Because ECP was not associated with any adverse reaction, the R patients continued such treatment for up to 3 years, showing a persisting eGFR stabilization. Twenty four hour proteinuria did not increase in the R patients over the follow-up when compared to the non-responder patients (NR). In the R patients, the HLAab levels were reduced and completely cleared in six out of eight patients when compared with the NR patients. The NR HLAab levels also increased after the discontinuation of the ECP. The ECP in the R patients showed a decrease in CD3, CD4, CD8, CD19, and NK circulating cells. The ECP treatment in the R patients also induced Tregs and Th17 cell increases, and a decrease of the IL-6 serum levels. CONCLUSIONS: ECP abates the HLAab titer and renal failure progression in patients with chronic renal ABMR, modulating the immune cellular and humoral responses.

Effects of Different Dialysis Strategies on Inflammatory Cytokine Profile in Maintenance Hemodialysis Patients with COVID-19: A Randomized Trial.

Uncontrolled inflammation plays a relevant role in the pathogenesis of coronavirus disease-19 (COVID-19). Here, we studied the time trend of inflammatory markers in a population of hemodialysis (HD) patients affected by COVID-19, undergoing two different dialysis approaches. In a prospective study, thirty-one maintenance HD patients with COVID-19 were randomized to expanded HD (HDx), performed using a medium cut-off membrane, or standard treatment using a protein-leaking dialyzer (PLD). Circulating levels of interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), soluble TLR4 (sTLR4), and interferon-gamma (IFN-γ), were collected at diagnosis, and one and two weeks after. Compared with 14 non-infected HD patients, COVID-19 patients showed lymphopenia and higher ferritin and lactate dehydrogenase levels. Moreover, COVID-19 patients had higher levels of IL-10 (15.2 (12.5) vs. 1.2 (1.4) pg/mL, p = 0.02). Twenty-nine patients were randomized to HDx (n = 15) or PLD (n = 14). After a single treatment, IL-8 showed a significant reduction in both groups, whereas IL-10 decreased only in HDx. All over the study, there were no significant modifications in circulating cytokine levels between the two groups, except for a parallel increase of IL-8 and IL-10 at one week control in the HDx group. No correlations were found between cytokine levels and clinical outcomes. In maintenance HD patients, COVID-19 is not related to a sustained inflammatory response. Therefore, modulation of inflammation seems not to be a suitable therapeutic target in this specific population.