Acute kidney injury pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Farima Kahe M.D. [2]


Acute kidney injury is defined as spontaneous deficit in kidney functions leading to urea retention and electrolyte imbalance. Etiologies of AKI can be divided based on pathophysiologic mechanisms into 3 broad categories: prerenal, intrinsic renal, and postrenal causes. Pre-renal AKI is most common and typically results from hypovolemia. Intrinsic renal is due to damage to renal paranchyma. Post-renal AKI is usually result of an obstruction, may be due to stones or strictures.



Etiologies of AKI can be divided based on pathophysiologic mechanisms into 3 broad categories: prerenal, intrinsic renal, and postrenal causes.

Prerenal AKI

  • Prerenal AKI, known as prerenal azotemia, is by far the most common cause of AKI representing 30-50% of all cases.
  • It is provoked by inadequate renal blood flow commonly due to decreased effective circulating blood flow.
  • This causes a decrease in the intraglomerular hydrostatic pressure required to achieve proper glomerular filtration.
  • As such, the pathophysiology of prerenal azotemia entails a drop in renal plasma flow beyond the capacity of autoregulation, a blunted or inadequate renal compensation for an otherwise tolerable change in perfusion, or a combination of both.
  • This eventually leads to ischemic renal injury particularly to the medulla which is maintained in hypoxic conditions at baseline.
  • Causes of prerenal injury are summarized in the figure below. To note, as prerenal AKI progresses with further ischemia, it transforms into acute tubular necrosis (ATN) crossing into the realm of intrinsic AKI.

Intrinsic Renal AKI

Intrinsic renal AKI generally occurs due to renal parenchymal injury and may be classified according to the site of injury into: glomerular, tubular, interstitial, and vascular.

Tubular AKI

Contrast-induced Nephropathy
  • Contrast induced nephropathy (CIN) recently called contrast induced AKI (CIAKI) is also major cause of intrinsic injury caused by iodinated contrast media used in cardiovascular imaging.
  • This entity is virtually non-existent in healthy young individuals.
  • Risk factors that increase susceptibility to CIN include advanced age, pre-existing CKD, diabetic nephropathy, severe heart failure, and concomitant exposure to other nephrotoxins.
    • The pathophysiology of CIN is not clearly understood; however, several attempts have been made to explain the underlying mechanism.
    • It is generally agreed that CIN is due to a combination of several influences brought on by contrast-media infusion rather than a single process.
    • The most important mechanism thought to be involved in CIN is a reduction in renal perfusion at the level of the microvasculature leading to tubular damage.
    • This is attributed to several alterations in the renal microenvironment including activation of the tubuloglomerular feeback, local vasoactive metabolites including adenosine, prostaglandin, NO, and endothelin as well as increased interstitial pressure.
    • Studies have also proposed injury to renal tubular cells may occur via a direct cytotoxic effect of the contrast media and via reactive oxygen species production.[13]

Glomerular AKI

Vascular AKI

Interstitial AKI

Postrenal AKI


There is no genetics associated with AKI.

Associated Conditions

Gross Pathology

  • On gross pathology, characteristic findings for AKI are not present.

Microscopic Pathology

  • On microscopic histopathological analysis, characteristic findings of AKI depends on the etiology of disease.


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