Acute kidney injury (AKI) is one of the most common serious complications for all hospital admissions, with its incidence increasing among hospitalized patients, particularly those in the intensive care unit. Despite significant improvements in critical care and dialysis technology, AKI is associated with an increased risk of short- and long-term mortality, prolonged hospital stays, and dialysis dependence. These risks are particularly relevant for critically ill patients with AKI severe enough to require renal replacement therapy (RRT). No specific pharmacologic treatment has been established to treat AKI. Hence, the mainstay treatment for patients with AKI is RRT even though there are still several problematic issues regarding its use including RRT modality, dose, and timing. Recently, the impact of AKI on an increased risk of progression to chronic kidney disease (CKD) and end-stage renal disease requiring dialysis or transplantation is attracting increased attention.
The annual incidence of acute kidney injury (AKI) has been increasing as the population ages. Despite advances in critical care and dialysis technology, the mortality remains unacceptably high in patients with AKI during the past few decades. Renal replacement therapy (RRT) is performed to treat patients with severe AKI and multiple organ failures, as well as to remove fluid in patients with fluid overload including those with acute heart failure and lung edema in the intensive care unit (ICU). The mortality in patients with AKI requiring RRT is higher than 50 %. RRT strategies in patients with AKI depend on various conditions. However, there is little consensus on when to start and stop RRT, its optimal dose, and the choice of different RRT modalities (intermittent versus (vs.) continuous) in patients with AKI. Patients with AKI in the ICU are preferentially treated with continuous rather than intermittent RRT (IRRT), usually because of hemodynamic stability and steady of solute clearance. At present, the type and dose of RRT are dependent on the experience of the attending clinicians, including intensivists and nephrologists.
Oxysterols, important regulators of cholesterol homeostasis in the brain, are affected by neurodegenerative diseases. Early-onset Alzheimer’s disease is associated with higher levels of circulating brain-derived 24S-hydroxycholesterol (24S-OHC). Conversion of cholesterol to 24S-OHC is mediated by cholesterol 24S-hydroxylase in the brain, which is the major pathway for oxysterol elimination, followed by oxidation through hepatic first-pass metabolism by CYP39A1. Abnormal CYP39A1 expression results in accumulation of 24S-OHC, influencing neurodegenerative disease-related deterioration; thus, it is important to understand the normal elimination of 24S-OHC and the system regulating CYP39A1, a selective hepatic metabolic enzyme of 24S-OHC. We examined the role of transcriptional regulation by retinoic acid receptor-related orphan receptor α (RORα), a nuclear receptor that responds to oxysterol ligands. In humans, the promoter and first intronic regions of CYP39A1 contain two putative RORα response elements (ROREs). RORα binding and responses of these ROREs were assessed using electrophoretic mobility shift, chromatin immunoprecipitation, and luciferase reporter assays. CYP39A1 was upregulated by RORα overexpression in HEK293 cells, while RORα knockdown by siRNA significantly downregulated CYP39A1 expression in human hepatoma cells. Additionally, CYP39A1 was induced by RORα agonist treatment, suggesting that CYP39A1 expression is activated by RORα nuclear receptors. This may provide a way to increase CYP39A1 activity using RORα agonists, and help halt 24S-OHC accumulation in neurodegenerative illnesses.
A 29-year-old woman was diagnosed with Henoch-Schönlein purpura nephritis (HSPN) based on the presence of purpura and histopathological findings showing crescent formation, mesangial proliferation and IgA deposition in the glomerular mesangium. She was treated with high-dose steroids; however, the nephritic syndrome persisted. Therefore, we diagnosed her with steroid-resistant HSPN and decided to add treatment with cyclosphamide pulse therapy. After one year of treatment, the histopathological findings, including crescent formation and IgA deposition, improved, as confirmed on a renal biopsy, and the patient fulfilled the criteria for complete remission. Cyclophosphamide pulse therapy may be considered an effective treatment for intractable HSPN.
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