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Pathogenesis and etiology of ischemic acute tubular necrosis

Mitchell H Rosner, MD
Mark D Okusa, MD
Section Editor
Paul M Palevsky, MD
Deputy Editor
Alice M Sheridan, MD


Patients who are hypotensive due to surgery, sepsis, bleeding, or other causes are at risk of developing ischemic acute tubular necrosis (ATN), especially if the impairment in renal perfusion is either severe or prolonged in duration. Patients may also suffer ischemic injury to the kidney due to interruptions in renal blood flow such as from cross-clamping of the renal artery during surgery for removal of renal cell carcinoma. This disorder is characterized by a rising plasma creatinine concentration, elevation in specific urine or serum biomarkers that are indicative of tubular injury such as kidney injury molecule-1 (KIM-1), a urine volume that may be reduced or normal, and a characteristic set of changes in the urinalysis, including many granular casts and a fractional excretion of sodium above 1 percent and fractional excretion of urea above 35 percent. Serum and urine biomarkers of tubular injury have been proposed as early biomarkers for the diagnosis of ATN [1].

The pathogenesis and etiology of ischemic ATN will be reviewed here [2-4]. The diagnosis of ATN, potential therapies for ischemic ATN, and other causes of ATN are discussed separately. (See "Possible prevention and therapy of ischemic acute tubular necrosis" and "Etiology and diagnosis of prerenal disease and acute tubular necrosis in acute kidney injury in adults" and "Manifestations of and risk factors for aminoglycoside nephrotoxicity" and "Clinical features and diagnosis of heme pigment-induced acute kidney injury" and "Pathogenesis, clinical features, and diagnosis of contrast-induced nephropathy".)


The process underlying ischemic ATN occurs in multiple phases, including prerenal (impairment in renal perfusion), initiation of injury, extension of injury, maintenance, and repair [5]. The major histologic changes in ATN are effacement and loss of proximal tubule brush border, patchy loss of tubule cells, focal areas of proximal tubule dilatation, distal tubule casts, and areas of cellular regeneration that appear during the phase of recovery of renal function (picture 1A-B) [6,7].

However, the decline in renal function is usually more prominent than the severity of the histologic changes. In some cases, necrotic cell death is not readily apparent and is restricted to the outer medullary regions (including the S3 segment of the proximal tubule and thick ascending limb of the loop of Henle). In addition to observable tubule obstruction and cell death, other factors may contribute to the decline in glomerular filtration rate (GFR) [6,8]:

Tubules from multiple nephrons drain into a single collecting tubule. As a result, obstruction in a relatively small number of collecting tubules may lead to failure of filtration in a large number of nephrons.

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Literature review current through: Nov 2017. | This topic last updated: May 10, 2017.
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