Clinical Outcomes of Remdesivir in COVID-19 Patients with Acute Kidney Injury or Chronic Kidney Disease: A Randomized Clinical Trial

Background: remdesivir is an RNA polymerase inhibitor approved to treat moderate to severe Coronavirus Disease 2019 (COVID-19); however, it has not yet been authenticated to apply to patients with acute kidney injury (AKI) or chronic kidney disease (CKD). Regarding some positive results obtained from previous studies, we aimed to evaluate the efficacy and safety of remdesivir in patients with COVID-19 with severe renal impairment.  Methods: In a randomized clinical trial, remdesivir was added to the standard regimen of treating patients with COVID-19 with AKI or CKD. 200 mg remdesivir was given on the first day of admission to 50 patients followed by 100 mg every other day until resolution of the symptoms. Clinical and paraclinical evaluation was performed daily and the findings were compared with the 50 patients on standard treatment regimen. Results: the rates of intensive care unit (ICU) admission (P: 0.02), and mortality (P: 0.007) were significantly reduced in patients who received remdesivir. Moreover, a substantial decrease of aspartate transaminase (AST) (P: 0.004), lactate dehydrogenase (LDH) (P: 0.004), ferritin (P: 0.007), erythrocyte sedimentation rate (ESR) (P<0.0001), alkaline phosphatase (ALP) (P: 0.006) were observed in the patients receiving remdesivir compared to the baseline values which was absent in case of non-remdesivir group. No serious side effects were observed, except for one patient who showed elevated liver enzymes. Conclusion: remdesivir appears to be well tolerated in patients with AKI and CKD. Administration of this drug resulted in reduced mortality and ICU admission as well as clinical and paraclinical improvement in these patients

Eculizumab in kidney diseases

The C5 inhibitor monoclonal antibody, eculizumab, has been approved for the treatment of atypical hemolytic uremic syndrome (aHUS) and paroxysmal nocturnal hemoglobinuria (PNH); however, the efficacy and safety of this drug in treating other complement-related renal diseases has not yet been elucidated. The high cost of eculizumab therapy and the rare adverse effects have created a paradox in conducting large clinical trials. Therefore, there is a need to increase clinicians’ awareness of the available data on the efficacy/safety of this drug in treating renal diseases. Herein, we have reviewed the outcomes of the administration of eculizumab in aHUS, PNH, lupus erythematosus nephritis, C3 glomerulonephritis, IgA nephropathy, and antibody-mediated rejection (AMR) in highly sensitized patients. Initial findings suggest its efficacy in treating acute injuries but lower effectiveness in preventing chronic lesions. Besides, early diagnosis and timely initiation of eculizumab are of particular importance

Toll-like receptor 4 in renal transplant

Toll-like receptor 4 is a member of the cell surface pattern recognition receptors involved in pathogenesis of several infectious and autoimmune diseases. The wide range of Toll-like receptor 4 extrinsic and intrinsic ligands means that it has considerable ability to trigger infectious and sterile inflammation, the latter assumed to be the principal cause of ischemia-reperfusion injury. With the rising number of renal transplant procedures using deceased donors, in addition to prolonged ischemia time due to organ transport and consequently increased risk of ischemia-induced injuries, the prevention of detrimental immune responses and/or overcoming these after they initiate could be beneficial for graft survival. This review aims to summarize past and present studies conducted about the role of Toll-like receptor 4 in early and late phases of transplant, including gene expression and polymorphism evaluations. © Başkent University 2018 Printed in Turkey. All rights reserved

Antiapoptotic Molecule Survivin in Transplantation: Helpful or Harmful?

Survivin, an antiapoptotic molecule from inhibitor of apoptosis protein (IAP) family, is most known for its implication in cancer as there are some efforts to apply it for diagnostic as well as therapeutic purposes in oncology. On the other hand, it could be a useful molecule to be positively targeted when trying to save tissue and promote cells viability. Since protecting the allograft from ischemia reperfusion injury and inflammation-induced damage is a considerable objective in transplantation, it is reasonable to take advantage from antiapoptotic agents like survivin in order to achieve this goal. However, survivin’s potential ability to induce malignancies makes some concerns about its use in clinic. The other barrier is this molecule’s involvement in lymphocytes development and proliferation which might increase the risk of graft rejection due to adaptive immune system overactivation. In this review we summarize the few studies carried out about survivin’s effect on graft survival and probable advantages and disadvantages of its overexpression in transplantation

Cytokines in Liver Transplantation

International audienc

Sirtuin 1: A Dilemma in Transplantation

Sirtuin 1, a member of sirtuin family of histone deacetylase enzymes, has been implicated in a variety of physiologic and pathologic events, including energy metabolism, cell survival, and age-related alterations. In view of the anti-inflammatory properties of sirtuin 1 along with its protective role in ischemia reperfusion injury, it might be considered as contributing to the promotion of transplantation outcome. However, the potential ability of sirtuin 1 to induce malignancies raises some concerns about its overexpression in clinic. Moreover, despite the findings of sirtuin 1 implication in thymic tolerance induction and T regulatory (Treg) cells survival, there is also evidence for its involvement in Treg suppression and in T helper 17 cells differentiation. The identification of sirtuin 1 natural and synthetic activators leads to the proposal of sirtuin 1 as an eligible target for clinical interventions in transplantation. All positive and negative consequences of sirtuin 1 overactivation/overexpression in the allograft should therefore be studied thoroughly. Herein, we summarize previous findings concerning direct and indirect influences of sirtuin 1 manipulation on transplantation

MicroRNAs-mediated regulation pathways in rheumatic diseases

Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are two common rheumatic disorders marked by persistent inflammatory joint disease. Patients with RA have osteodestructive symptoms, but those with AS have osteoproliferative manifestations. Ligaments, joints, tendons, bones, and muscles are all affected by rheumatic disorders. In recent years, many epigenetic factors contributing to the pathogenesis of rheumatoid disorders have been studied. MicroRNAs (miRNAs) are small, non-coding RNA molecules implicated as potential therapeutic targets or biomarkers in rheumatic diseases. MiRNAs play a critical role in the modulation of bone homeostasis and joint remodeling by controlling fibroblast-like synoviocytes (FLSs), chondrocytes, and osteocytes. Several miRNAs have been shown to be dysregulated in rheumatic diseases, including miR-10a, 16, 17, 18a, 19, 20a, 21, 27a, 29a, 34a, 103a, 125b, 132, 137, 143, 145, 146a, 155, 192, 203, 221, 222, 301a, 346, and 548a.The major molecular pathways governed by miRNAs in these cells are Wnt, bone-morphogenic protein (BMP), nuclear factor (NF)-kappa B, receptor activator of NF-kappa B (RANK)-RANK ligand (RANKL), and macrophage colony-stimulating factor (M-CSF) receptor pathway. This review aimed to provide an overview of the most important signaling pathways controlled by miRNAs in rheumatic diseases