What is the cause of Acute Tubular Necrosis? (Select one or more answers)

A. Increased BUN/Creatinine: Elevated BUN and creatinine levels reflect impaired renal function and reduced glomerular filtration. These findings are laboratory consequences of acute tubular necrosis rather than initiating causes. They help confirm kidney injury but do not trigger tubular damage. B. Ischemia: Prolonged renal hypoperfusion leads to oxygen deprivation of tubular cells, resulting in cellular injury and necrosis. Common causes include hypotension, shock, or severe blood loss. Ischemia is one of the most frequent underlying mechanisms of acute tubular necrosis. C. Anemia: Anemia reduces oxygen-carrying capacity but does not directly cause tubular cell necrosis. While severe anemia may contribute to overall tissue hypoxia, it is not a primary or direct cause of acute tubular necrosis. D. Sepsis: Sepsis causes systemic inflammation, hypotension, and impaired microcirculation, all of which reduce renal perfusion. Inflammatory mediators further damage renal tubular cells. This combination places patients at high risk for developing acute tubular necrosis. E. Nephrotoxins: Exposure to nephrotoxic substances such as aminoglycosides, contrast media, or heavy metals can directly injure renal tubular cells. Toxic damage disrupts cellular metabolism and integrity, leading to necrosis. Nephrotoxins are a common non-ischemic cause of acute tubular necrosis.