Introduction to Acute Kidney Injury

Acute kidney injury (AKI) is defined as an abrupt decrease in kidney function that occurs over the course of hours to days and results in changes to urine production, waste elimination, and the important homeostatic functions of the kidney. Synonyms for AKI include acute renal injury, acute kidney failure, and acute renal failure, however the terms that include “failure” are considered outdated and are no longer actively being used.

Types of AKI

As demonstrated above, the definition of AKI is very broad. Therefore, AKI is truly an umbrella term for many disease entities. These causes of AKI fall into 3 major categories:

1. Prerenal: Injury to the kidney caused by decreased renal blood flow. In order for the kidneys to filter the blood and modify the filtrate to produce urine, they need adequate blood flow. Additionally, the cells of the nephron tubules are highly metabolically active and so require adequate oxygen and nutrition in order to function, so decreased blood flow causes dysfunction and possibly death of these cells. Therefore, any disease state that causes decreased renal or systemic perfusion can cause prerenal AKI, including extreme hypotension, blood loss, and vasoconstriction of the renal arteries.
2. Renal or intrarenal: Direct injury to the renal tubules or glomeruli. A variety of conditions can cause this type of AKI and examples of these will be provided later in the chapter.
3. Postrenal: Alteration of kidney function caused by obstruction downstream of the kidney that causes pressure backup in the urinary system and disrupts the glomerular pressure gradient. Recall that blood is filtered in the glomerulus from the bloodstream into the renal tubules and this process relies on the pressure in the capillary being higher than that in Bowman’s space. If pressure in the urinary system increases, increasing the pressure in Bowman’s space, this filtration will not be able to occur normally.

Prerenal AKI

Prerenal AKI can be subcategorized into cases where there is a decrease in absolute blood volume and cases where there is a decrease in effective blood volume. A decrease in absolute blood volume describes a loss of blood or fluid, such as from a massive hemorrhage (bleed), dehydration, or excessive diarrhea or vomiting. A decrease in effective blood volume means that the body has not lost fluid, but the blood is unable to circulate properly. There are many causes for this, some include congestive heart failure (a loss of heart muscle function, such that it is no longer able to pump adequately), sepsis (excessive blood vessel dilation due to a systemic inflammatory response), or a blockage in the vasculature, such as a pulmonary embolism (blood clot in the blood vessels of the lung). These are all causes of medical shock, which is defined as a sudden drop in blood flow to the body and may be caused by decreases in absolute or effective blood volume.

In some cases, the decrease in blood flow is specific to the kidneys. For example, hepatorenal syndrome occurs in liver disease when hormones are released that cause excessive renal vasoconstriction. Certain drugs also impact the ability of the glomeruli to maintain filtration and may also cause prerenal AKI if used incorrectly.

Intrarenal AKI

Intrarenal AKI can involve disease processes at the level of the glomeruli, the renal tubules, or the interstitium (fluid filled spaces around the cells) of the kidney.

The most common cause of intrarenal AKI is called acute tubular necrosis (ATN) and occurs when ischemia (inadequate blood flow) or a toxin damages the renal tubules and causes the cells that line them to undergo necrosis (cell death). A prolonged prerenal AKI can progress to ATN if the decreased blood flow to the kidneys begins to result in necrosis of the cells in the tubules.

An example of an intrarenal cause of AKI affecting the glomerulus is glomerulonephritis. Glomerulonephritis also has a variety of causes, but most are related to autoimmune conditions such as lupus. It can also occur after certain infections such as streptococcus (eg: “strep throat”) where the infection triggers a type of allergic reaction that results in deposition of immune system components like antibodies and immune cells in the glomeruli. The immune deposits activate an inflammatory response which damages the glomeruli and interferes with their function.

A problem that can occur in the interstitium of the kidney is acute interstitial nephritis. This is similar to an allergic reaction within the interstitial spaces of the kidney and is usually caused by a reaction to a new medication. Clinically, this may present with a rash, fever, and increased number of eosinophils, a type of white blood cell associated with allergic reactions and parasitic infections, in the blood.

Postrenal AKI

Any obstruction of the urinary system downstream of the kidney has the potential to cause a postrenal AKI. Examples include blockage of the ureter or urethra by a kidney or bladder stone, scar tissue, tumour, or benign prostatic hypertrophy (BPH) (enlarged prostate gland) (biological males only). BPH is the most common cause of post-renal AKI, especially in older males.

In cases where the obstruction is gradual and affects only one kidney, for example a tumour compressing one of the two ureters, AKI is usually not the result. This is because only one of the kidneys is affected and over time the other is usually able to compensate. Therefore, it is more common for obstruction of the bladder outlet to cause AKI, seeing as there is only one urethra, but two kidneys and two ureters.

Section Summary

AKI occurs when the kidney(s) are injured suddenly and significantly such that many nephrons are damaged or even die.  Causes of AKI are various but can be classified based on the location of the injury.  Pre-renal causes result in decreased blood flow to the kidney, thus preventing both perfusion of the kidney and filtration of blood. This can be due to either low blood volume or low blood flow to the kidneys specifically. Intrarenal causes tend to cause direct damage to the nephrons – whether it be chemical (e.g. drugs), immunologic (eg. nephritis), or physical.  Post-renal causes are most commonly caused by obstructions in the urinary tract (e.g. kidney stones, benign prostatic hyperplasia) that causes a back up of urine into the kidneys causing physical damage with the backpressure.

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