Fecal Microbiota Transplantation in Reducing Uremic Toxins Accumulation in Kidney Disease: Current Understanding and Future Perspectives.

During the past decades, the gut microbiome emerged as a key player in kidney disease. Dysbiosis-related uremic toxins together with pro-inflammatory mediators are the main factors in a deteriorating kidney function. The toxicity of uremic compounds has been well-documented in a plethora of pathophysiological mechanisms in kidney disease, such as cardiovascular injury (CVI), metabolic dysfunction, and inflammation. Accumulating data on the detrimental effect of uremic solutes in kidney disease supported the development of many strategies to restore eubiosis. Fecal microbiota transplantation (FMT) spread as an encouraging treatment for different dysbiosis-associated disorders. In this scenario, flourishing studies indicate that fecal transplantation could represent a novel treatment to reduce the uremic toxins accumulation. Here, we present the state-of-the-art concerning the application of FMT on kidney disease to restore eubiosis and reverse the retention of uremic toxins.

Acute Kidney Injury in Kidney Transplant Patients in Intensive Care Unit: From Pathogenesis to Clinical Management.

Kidney transplantation is the first-choice treatment for end-stage renal disease (ESRD). Kidney transplant recipients (KTRs) are at higher risk of experiencing a life-threatening event requiring intensive care unit (ICU) admission, mainly in the late post-transplant period (more than 6 months after transplantation). Urosepsis and bloodstream infections account for almost half of ICU admissions in this population; in addition, potential side effects related to immunosuppressive treatment should be accounted for cytotoxic and ischemic changes induced by calcineurin inhibitor (CNI), sirolimus/CNI-induced thrombotic microangiopathy and posterior reversible encephalopathy syndrome. Throughout the ICU stay, Acute Kidney Injury (AKI) incidence is common and ranges from 10% to 80%, and up to 40% will require renal replacement therapy. In-hospital mortality can reach 30% and correlates with acute illness severity and admission diagnosis. Graft survival is subordinated to baseline estimated glomerular filtration rate (eGFR), clinical presentation, disease severity and potential drug nephrotoxicity. The present review aims to define the impact of AKI events on short- and long-term outcomes in KTRs, focusing on the epidemiologic data regarding AKI incidence in this subpopulation; the pathophysiological mechanisms underlying AKI development and potential AKI biomarkers in kidney transplantation, graft and patients' outcomes; the current diagnostic work up and management of AKI; and the modulation of immunosuppression in ICU-admitted KTRs.

Methods to Study Posttranslational Modification Patterns in Cytotoxic T-Cells and Cancer.

Protein posttranslational modifications (PTMs) regulate intracellular signaling associated with development and progression of many diseases; thus, they are key to understanding pathological mechanisms and set up more tailored therapies. In addition, many posttranslationally modified proteins are released into biological fluids and can be used as new and more specific biomarkers. Based on this evidence, we analyzed the role of some PTMs in cancer and described the correlation between specific PTMs and T-cells activation/inhibition in cancer microenvironment. In the second part of this chapter, we analyzed the most commonly used approaches for qualitative and quantitative determination of PTMs. The comparison of three distinct but often complementary methodologies such as immunoblotting, mass spectrometry, and ELISA assays has allowed to highlight the pros and cons of each approach with a focus on their current application and their future developments to obtain more confident biomarkers and therapeutic targets useful for diagnosis, prognosis, and monitoring of the response to therapy.