KDIGO Clinical Practice Guideline for Acute Kidney Injury
Acute tubular necrosis (ATN)

Acute tubular necrosis (ATN)

When mammalian kidneys are subjected to prolonged warm ischemia followed by reperfusion, there is extensive necrosis destroying the proximal tubules of the outer stripe of the medulla, and the proximal convoluted tubules become necrotic as well.¹⁰ Distal nephron involvement in these animal experiments is minimal, unless medullary oxygenation is specifically targeted.¹¹ Although these animals develop severe ARF, as noted by Rosen and Heyman, not much else resembles the clinical syndrome in humans.¹² Indeed these authors correctly point out that the term ‘‘acute tubular necrosis does not accurately reflect the morphological changes in this condition’’.¹² Instead, the term ATN is used to describe a clinical situation in which there is adequate renal perfusion to largely maintain tubular integrity, but not to sustain glomerular filtration. Data from renal biopsies in patients with ATN dating back to the 1950s¹³ confirm the limited parenchymal compromise in spite of severe organ dysfunction.¹² Thus, the syndrome of ATN has very little to do with the animal models traditionally used to study it. More recently, investigators have emphasized the role of endothelial dysfunction, coagulation abnormalities, systemic inflammation, endothelial dysfunction, and oxidative stress in causing renal injury, particularly in the setting of sepsis.^14,15 True ATN does, in fact, occur. For example, patients with arterial catastrophes (ruptured aneurysms, acute dissection) can suffer prolonged periods of warm ischemia just like animal models. However, these cases comprise only a small fraction of patients with AKI, and ironically, these patients are often excluded from studies seeking to enroll patients with the more common clinical syndrome known as ATN.