As mentioned in a previous section, AKI is a clinical diagnosis defined by an increase in serum creatinine or an abnormal decrease in urine output. Therefore, when discussing histopathology, the term AKI doesn’t really apply and instead we describe the pathological changes we see within the kidney itself.

The categories of causes of AKI (prerenal, intrarenal, and postrenal) don’t apply to the histopathology either. Generally, we will see only intrarenal damage when observing the kidneys microscopically, but this could be a result of any of AKI from any of the 3 categories.

Review the following sections and videos to learn more about the histopathology of AKI.

Shock Kidney

As we discussed earlier, medical shock occurs when there is a serious decrease in either effective or absolute circulating blood volume and may cause a prerenal AKI. A persistent prerenal AKI can cause intrarenal kidney damage, when the high metabolic demands of the cells in the renal tubules are not met and they begin to degenerate.

The following video reviews the histological findings in the kidney of someone with hemorrhagic shock.

^{Histopathology of kidney experiencing shock. DHPLC specimen PATH 425-058 presented by Lyz Boyd
Video Summary – Clinical context: The patient was a 29 year old male who was involved in a traffic accident and fractured his pelvis. Pelvic fractures are often associated with massive internal bleeding, which in this case caused shock and therefore a prerenal cause of AKI. He developed AKI and died 7 days later.
Pathology: The blood loss caused hemorrhagic shock which resulted in a type of prerenal kidney injury. Prolonged lack of blood to the kidneys resulted in pathology that can be seen microscopically, termed acute tubular injury.
Histopathological findings: The following changes to the renal tubules can be observed:
– Renal tubules are filled with debris and/or blood as a result of damage to the tubules and degradation of the epithelial cells lining the tubules.
– Nuclei of the cells lining the tubules disappear or appear faint.
– The brush border of the proximal convoluted tubules is lost or reduced.
– The cells lining the tubules flatten, making the lining of the tubules appear thinner.
– Mitotic figures are present, indicating that the surviving cells are attempting to divide and regenerate the tubules.}

Glomerulonephritis

The term glomerulonephritis encompasses a group of causes of kidney disease that all involve damage done to components of the glomerulus by the immune system. For example systemic lupus erythematosus (colloquially known as “lupus”) is an autoimmune condition that involves deposition of immune complexes and inflammatory responses in a wide array of body systems. One of these is the kidneys and this ongoing immune insult to the kidneys may affect renal function. Refer to Systemic Lupus Erythematosus for more detail.

Another example of a cause of glomerulonephritis is post-streptococcal glomerulonephritis. After an infection with streptococcal bacteria, some people develop a damaging immune response in the kidneys that affects the glomeruli. There are many other causes of glomerulonephritis, but in most cases the recruitment of immune cells and proteins (like antibodies) impair the ability of the glomerulus to perform filtration. Not all of these causes usually result in AKI; some of them have a tendency to cause more gradual changes to kidney function which is termed Chronic Kidney Disease (CKD).

The impaired filtration and damage to the glomeruli results in protein and red blood cells that would normally be too large for the filtration barrier of the glomerulus leaking into the urine. This can result in inadequate protein in the blood, decreasing the osmotic force drawing fluid back into the blood and resulting in edema. The nephron has an internal mechanism of sensing filtration and adjusting blood pressure accordingly, so when filtration is impaired, factors are released in an attempt to increase kidney perfusion. Unlike prerenal causes where activation of mechanisms to raise blood pressure may be helpful, in glomerulonephritis the systemic blood pressure is usually normal to begin with, so this effect may cause dangerously elevated blood pressure.

In the case of the specimen we will see shortly, clinicians were unable to determine a precise cause, but acute glomerulonephritis was confirmed to be present.

The following video outlines the histopathological findings of glomerulonephritis.

^{Histopathology of glomerulonephritis. DHPLC specimen PATH 425-049 presented by Lyz Boyd
Video Summary:
Clinical context: The patient was a 10 year old child who had a strep throat infection, which is an infection with a bacteria called streptococcus. A couple of weeks later they developed fever, edema, headaches, and “smoky” urine. Their urine contained protein, red blood cells, and white blood cells and their blood contained excess urea, a metabolic waste product.
Pathology: In some cases, a streptococcus infection results in a misguided immune response that attacks the glomeruli of the kidneys, termed streptococcal glomerulonephritis.
Histopathological findings:
– The tubules of the kidney have observable debris and damage, similar to the shock kidney.
– The glomeruli are hypercellular because they are filled with inflammatory cells that are impairing the function of the glomeruli.
– Some glomeruli demonstrate crescents, which are areas of scarring in response to the inflammatory damage; others have been entirely obliterated.}

Section Review

Histologically, the damage caused in AKI is quite dramatic. In shock kidney, blood is not perfusing the nephrons causing starvation and death of cells. As a result, the nephron tubules are filled with debris and/or blood with signs of nuclear activity (i.e. life in the cell) waning as cellular structures appear faint (e.g. nuclei) or diminished (e.g. loss of brush border in PCT, flattened cells). Similarly in glomerulonephritis, the damage to glomeruli by antibody complexes are evident in observable debris and damage in the nephrons. Glomeruli are hypercellular because they are filled with inflammatory cells in addition to the glomerular capillaries and blood. Taken together with the changes in gross anatomy, the damage to nephrons are serious. 

Review Questions