Acute tubular necrosis

Introduction

Acute kidney injury is a common clinical problem in the hospital, especially in the intensive care unit. The two most important causes of acute kidney injury in the hospital are prerenal kidney failure and acute tubular necrosis (ATN). Prerenal kidney failure is due to poor renal blood flow with a fall in GFR, and is potentially quickly reversible with correction of the renal blood flow. If the reduced perfusion remains over a long period, ischemic damage to the tubule cells occurs and ATN develops. ATN can also be a result of nephrotoxins and sepsis, and is not immediately reversible.

Causes

The tubule cells have a quite high metabolic activity rate as the ion pumps require a lot of energy. Even though the kidneys usually have a high blood flow (20-25 % of the minute volume goes to the kidneys), the meduallary perfusion is vulnerable. Ischemia of tubule cells will lead to death, shedding of cells in the tubules and an acute drop in GFR. Nephrotoxins can lead to ATN through direct injury or by affecting the peritubular circulation, and thereby ischemic damage of the tubule cells as a result.

Table of the most common causes of ATN:

Causes Examples

Prerenal causes Dehydration

Hypotension

Reduced circulating volume

Selective renal ischemia

NSAIDs

ACE inhibitors in combination with the above

Sepsis

Nephrotoxins Aminoglycosides

Free myoglobin an hemoglobin

Cisplatin

Contrast containing iodine

Antiviral drugs

Causes	Examples
Prerenal causes	Dehydration
	Hypotension
	Reduced circulating volume
	Selective renal ischemia
	NSAIDs
	ACE inhibitors in combination with the above
Sepsis
Nephrotoxins	Aminoglycosides
	Free myoglobin an hemoglobin
	Cisplatin
	Contrast containing iodine
	Antiviral drugs

Clinical presentation

Affected patients present with acute kidney injury with a quickly rising creatinine. The kidney failure can be both oliguric and non-oliguric.

Urinalysis

In contrast with prerenal kidney failure, where the urine sediment is normal and the patient produces a concentrated urine where the sodium is reabsorbed, the patient with ANT will have a urine sediment abundant with granular casts and cellular casts due to the shedding of dead tubule cells. In ATN, the tubule function is affected and classically, the fractional excretion of sodium is elevated as a sign of this. (Picture of ATN in urine microscopy).

Histopathology

One can see necrosis of epithelial cells in the tubule, interstitial bleeding and leukocyte infiltration

Prognosis and treatment

The treatment is targeted towards removing the nephrotoxic substance that is not vital and strives to recover renal perfusion. Tubule cells have a good potential for regeneration and the prognosis is good. Typically, the kidney function normalises after 6-12 weeks after an episode with ATN, but chronic kidney injury can be the result in severe cases of ATN.