Mitochondrial dysfunction is important in the pathogenesis of various kidney diseases and the mitochondria potentially serve as therapeutic targets necessitating further investigation. Alterations in mitochondrial biogenesis, imbalance between fusion and fission processes leading to mitochondrial fragmentation, oxidative stress, release of cytochrome c and mitochondrial DNA resulting in apoptosis, mitophagy, and defects in energy metabolism are the key pathophysiological mechanisms underlying the role of mitochondrial dysfunction in kidney diseases. Currently, various strategies target the mitochondria to improve kidney function and kidney treatment. The agents used in these strategies can be classified as biogenesis activators, fission inhibitors, antioxidants, mPTP inhibitors, and agents which enhance mitophagy and cardiolipin-protective drugs. Several glucose-lowering drugs, such as glucagon-like peptide-1 receptor agonists (GLP-1-RA) and sodium glucose co-transporter-2 (SGLT-2) inhibitors are also known to have influences on these mechanisms. In this review, we delineate the role of mitochondrial dysfunction in kidney disease, the current mitochondria-targeting treatment options affecting the kidneys and the future role of mitochondria in kidney pathology.

Chronic kidney disease (CKD) is one of the most important public health concerns of the century, and is associated with high rates of morbidity, mortality and social costs. CKD evolving towards end-stage kidney disease (ESKD) is on the rise resulting in a greater number of patients requiring peritoneal dialysis (PD) and hemodialysis (HD). The aim of this manuscript is to review the current literature on the interplay of residual renal function (RRF) with clinical outcomes in ESKD. The persistence of RRF is one of the most important predictors of decreased morbidity, mortality, and better quality of life in both PD and HD patients. RRF contributes to the well-being of ESKD patients through various mechanisms including higher clearance of solutes, maintenance of fluid balance, removal of uremic toxins and control of electrolytes. Furthermore, RRF has beneficial effects on inflammation, anemia, malnutrition, diabetes mellitus, obesity, changes in the microbiota, and cardiac diseases. Several strategies have been proposed to preserve RRF, such as blockade of the renin–angiotensin–aldosterone system, better blood pressure control, incremental PD and HD. Several clinical trials investigating the issue of preservation of RRF are ongoing. They are needed to broaden our understanding of the interplay of RRF with clinical outcomes in ESKD. Graphical abstract

Background Acute kidney injury (AKI) in COVID-19 patients is associated with poor prognosis. However, the incidence, risk factors and potential outcomes of AKI in hospitalized patients are not well studied. Materials and methods This is a retrospective cohort study conducted in two major university hospitals. Electronic health records of the patients, 18 years or older, hospitalized between 13 April and 1 June 2020 with confirmed COVID-19 were reviewed. We described the incidence and the risk factors for AKI development in COVID-19 patients. Furthermore, we investigated the effects of AKI on the length of hospital and intensive care unit (ICU) stay, the admission rates to ICU, the percentage of patients with cytokine storm and in-hospital mortality rate. Results Among 770 hospitalized patients included in this study, 92 (11.9%) patients developed AKI. The length of hospitalized days (16 vs 9.9, p < 0.001) and days spent in the hospital until ICU admission (3.5 vs. 2.5, p = 0.003) were higher in the AKI group compared to patients without AKI. In addition, ICU admission rates were also significantly higher in patients with AKI (63% vs. 20.7%, p < 0.001). The percentage of patients with AKI who developed cytokine storm was significantly higher than patients without AKI (25.9% vs. 14%, p = 0.009). Furthermore, the in-hospital mortality rate was significantly higher in patients with AKI (47.2% vs. 4.7%, p < 0.001). Conclusions AKI is common in hospitalized COVID-19 patients. Furthermore, we show that AKI increases the admission rates to ICU and in-hospital mortality. Our findings suggest that AKI should be effectively managed to prevent the adverse outcomes in COVID-19 patients.

Kidney transplant recipients and dialysis patients constitute a risk group for severe COVID-19. They are highly advised to get vaccinated according to the current guidelines. However, data on antibody response, cell responses and protection from events, and factors that might alter this response after a routine full series of vaccination remain incomplete for these populations. The aim of this article was to analyze the antibody responses after a full series of mRNA-based SARS-CoV-2 vaccination in kidney transplantation and dialysis patients and to define the factors that alter seroconversion status in these populations. In this systematic review, 18 studies investigating the antibody response to full vaccination with two doses of COVID-19 mRNA vaccines in hemodialysis, peritoneal dialysis, and kidney transplant patients were included. Kidney transplant and dialysis patients have a lower seroconversion rate after mRNA-based SARS-CoV-2 vaccination than the healthy population: 27.2% for kidney transplantation, 88.5% for dialysis patients while all healthy control in these studies seroconverted. Moreover, anti-S antibody titers were lower in seroconverted kidney transplantation or dialysis patients than in healthy control in all studies that assessed this variable. Older age and dialysis vintage, immunosuppressive or chemotherapy treatment, and lower serum albumin, white blood cell, lymphocyte and hemoglobin counts were associated with lower/no antibody response to vaccination. Dialysis patients and kidney transplant recipients have lower seroconversion rates after a full series of mRNA-based SARS-CoV-2 vaccination than the general population. Several factors are associated with an altered antibody response. A third dose could be considered in this patient group.

The best treatment for patients with end-stage kidney disease is kidney transplantation, which, if successful provides both a reduction in mortality and a better quality of life compared to dialysis. Although there has been significant improvement in short-term outcomes after kidney transplantation, long-term graft survival still remains insufficient. As a result, there has been an increase in the number of individuals who need dialysis again after kidney transplant failure, and increasingly contribute to kidney transplant waiting lists. Starting dialysis after graft failure is a difficult task not only for the patients, but also for the nephrologists and the care team. Furthermore, recommendations for management of dialysis after kidney graft loss are lacking. Aim of this narrative review is to provide a perspective on the role of dialysis in the management of patients with failed kidney allograft. Although numerous studies have reported higher mortality in patients undergoing dialysis following kidney allograft failure, reports are contrasting. A patient-centered, individualized approach should drive the choices of initiating dialysis, dialysis modality, maintenance of immunosuppressive drugs and vascular access. Graphical abstract

E3 ubiquitin ligases mediating turnover of proteins engaged in cancer progression point to key regulatory nodes. To uncover modifiers of metastatic competency, we conducted an in vivo genome-wide CRISPR-inactivation screen using cultured breast circulating tumor cells, following intravascular seeding and lung colonization. We identified HECTD4, a previously uncharacterized gene encoding a conserved potential homologous to E6AP C-terminus domain-containing ubiquitin transferase, as a potent tumor and metastasis suppressor. We show that purified HECTD4 mediates ubiquitin conjugation in vitro, and proteomic studies combined with ubiquitin remnant profiling identify a major degradation target as the prostaglandin synthetic enzyme cyclooxygenase-2 (COX-2; PTGS2). In addition to COX-2 itself, HECTD4 targets its regulatory kinase MKK7. In breast cancer models, HECTD4 expression is induced as cells lose adherence to the matrix, and its depletion massively increases COX-2 expression, enhancing anchorage-independent proliferation and tumorigenesis. Genetic or pharmacologic suppression of COX-2 reverses the protumorigenic and prometastatic phenotype of HECTD4-depleted cells. Thus, HECTD4 encodes an E3 ubiquitin ligase that downregulates COX-2 suppressing anchorage independence in epithelial cancer cells.