Acute Tubular Necrosis

• Intrarenal pathology.
• Can cause acute kidney injury, which is characterized by increased creatinine and decreased urine volume.

Tubule necrosis leads to impaired filtration and increased NaCl delivery to the macula densa. As a result, the tubuloglomerular feedback mechanism of GFR regulation is activated, and GFR is reduced. Recall that reduced GFR can lead to azotemia and uremia (see the links in our notes for more information). Acute tubular necrosis can be caused by low blood flow to the kidneys or exposure to toxic substances. Ischemic causes include hypotension, surgery, and sepsis; essentially, any event that contributes to pre-renal acute kidney injury can also contribute to acute tubular necrosis. Be aware that, in addition to hemodynamic effects, sepsis also has detrimental inflammatory effects on the tubules. Toxins: Several endogenous and exogenous toxins can damage the renal tubules.

• Excessive quantities of myoglobin and hemoglobin damage the tubules via direct and indirect mechanisms (for example, we see ATN in rhabdomyolysis and massive hemolysis).

• Iondated radiocontrast agents used in imaging technologies tend to cause self-limited and reversible elevations in serum creatinine, but long-term renal and/or cardiovascular problems can occur.

• Contrast nephropathy usually appears within 24-72 hours of administration.

• Hyperuricemia, as we see in patients with tumor lysis syndrome and gout, induces inflammatory reactions in the tubules.

• Various poisons, including ethylene glycol and mercury, trigger tubular necrosis.

• Several drugs, including aminoglycosides, vancomycin, chemo drugs, and NSAIDs, are toxic to the renal tubules.

1. The inciting event (ischemia or necrosis). 2. Maintenance phase, which comprises 1-3 weeks of oliguria with declining renal functioning. 3. Recovery phase, which is characterized by polyuria with falling serum creatinine and BUN. ATN is a common cause of renal failure in older patients, those with other kidney diseases and/or diabetes, and those who are hospitalized with other critical illnesses. In the urine, we look for muddy brown casts and renal tubular epithelial cells. FENa > 2% (except in the case of contrast nephropathy, which is often < 1%). Histopathology: Focal necrosis and apoptosis, with cells and cellular debris in the tubule lumens; may also see increased mitotic activity in tubules undergoing repair. Tubules have wide, cluttered lumens with smaller tubule cells and ragged edges. Histopathology may reflect the specific etiology: When excessive hemoglobin or myoglobin is the cause, we see red-brown casts in the distal and collecting tubules. In mercury poisoning, we see large acidophilic inclusions. In ethylene glycol poisoning, we see calcium oxalate crystals. There are no specific treatments for acute tubular necrosis, but we can give patients supportive care with fluid and electrolytes, and, when possible, address the root causes (correct the hemodynamic imbalance, remove exposure to toxins).