Renal azotemia

Definitions & Key takeaways

Renal azotemia refers to an elevation of nitrogen-containing waste products in blood like urea and creatinine, which are due to renal dysfunction often causing an acute kidney injury (AKI). AKI is said when the kidneys aren't functioning at 100%, and it has developed relatively quickly, typically over a few days.

AKI can be classified into three main types: intrarenal, prerenal, and postrenal AKI. In intrarenal AKI, kidney injury is caused by something within the kidneys themselves. Examples include conditions like acute tubular necrosis, glomerulonephritis, or acute interstitial nephritis. In prerenal AKI, there is reduced blood flow to the kidneys, and this hypoperfusion results in kidney injury. It's commonly seen following dehydration, or shock (e.g. hypovolemic and septic shocks). In postrenal AKI, a blockage in the urinary tract prevents urine from leaving the kidneys, which impairs normal kidney functioning and damages them. Postrenal AKI can be caused by conditions like bladder stones, prostate enlargement in men, or urinary tract tumors.

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Acute kidney injury, or AKI, is when the kidney isn’t functioning at 100% and that decrease in function develops relatively quickly, typically over a few days.
Actually, AKI used to be known as acute renal failure, or ARF, but AKI is a broader term that also includes subtle decreases in kidney function.
AKI can essentially be split into three types, prerenal AKI meaning the cause of kidney injury’s coming before the kidneys, postrenal AKI—meaning after the kidneys, or intrarenal AKI—meaning within the kidneys.
Now the kidney’s job is to regulate what’s in the blood, so they might remove waste, or make sure electrolyte levels are steady, or regulate the overall amount of water, and even make hormones - the kidneys do a lot of stuff!
Blood gets into the kidney through the renal artery, into tiny clumps of arterioles called glomeruli where it’s initially filtered, with the filtrate, the stuff filtered out, moving into the renal tubule.
Sometimes fluid or electrolytes can move back from the filtrate into the blood - called reabsorption, and sometimes more fluid or electrolytes can move from the blood to the fitrate - called secretion.
Along with fluid and electrolytes, though, waste-containing compounds are also filtered, like urea and creatinine, although some urea is actually reabsorbed back into the blood, whereas only a little bit of creatinine is reabsorbed.
In fact, in the blood, the normal ratio of blood urea nitrogen, or BUN, to creatinine is between 5 and 20 to 1—meaning the blood carries 5 to 20 molecules of urea for every one molecule of creatinine, and this is a pretty good diagnostic for looking at kidney function!
Ultimately the filtrate is turned into urine and is excreted from the kidney through the ureter, into the bladder, and peed away.
Meanwhile, the filtered blood drains into the renal vein. Typically intrarenal AKI’s due to damage to the tubules, the glomerulus, or the interstitium—the space between tubules.
Starting with the tubules and the most common cause of intrarenal AKI, which is acute tubular necrosis. Which is where the epithelial cells that line the tubules necrose, or die.
One way this can happen is via ischemia, or a lack of blood supply to the cells. A lot of times acute tubular necrosis due to ischemia is caused by some prerenal acute kidney injury, since prerenal AKI results in less blood sent to the kidneys, and those epithelial cells need oxygen from the blood just like any other cells.
In fact, all that secretion and reabsorption in the tubules takes a lot of energy, and so these cells are particularly sensitive to a loss of blood supply, especially the cells in the proximal tubule and medullary segment of the thick ascending limb.
The other way epithelial cells can necrose is via nephrotoxins, which are substances that tend to damage the epithelial tubular cells.
A few of the common ones being aminoglycosides—a group of antibiotics, heavy metals like lead, myoglobin released from damaged muscles, ethylene glycol—essentially anti-freeze which is naturally sweet tasting and therefore a risk for poisoning children, radiocontrast dye, and uric acid.
That last one, uric acid, is a waste product that can build up when cells die during cancer treatment, called tumor lysis syndrome, and is the reason why staying well hydrated to improve flow through the tubules as well as using medications like allopurinol and urate oxidase to lower uric acid levels can be so important while on certain chemotherapy.
Whatever the cause of cell death is, when those cells die, they slough off into the tubule, and basically build up and plug the tubule, which, just like in postrenal AKI, generates higher pressures in the tubules, which means fluid’s essentially trying to flow from high pressure arterioles to high pressure tubules...which doesn’t really work very well and the fluid filtered across is lowered, which lowers the glomerular filtration rate or GFR, which is how much blood the kidneys filter in mL through their glomeruli per minute.
With less blood being filtered, less urine is produced, called oliguria, abnormally low urine production, and less urea and creatinine get filtered out, so more stays in the blood, called azotemia, high levels of nitrogen-containing compounds in the blood.
Along with that, dead cells aren’t very good at reabsorbing or secreting molecules anymore, right? So other things start to build up in the blood as well, like potassium, called hyperkalemia, as well as acids, called metabolic acidosis.
Also, these dead clumped up cells in the tubule form a brown granular cast which will eventually get excreted in the urine.
It’s called a cast because it stays in essentially the same cylindrical shape as the tubule. If the underlying cause of the acute tubular necrosis is addressed, people can recover, because tubular cells can typically regenerate over the course of a few weeks.
Alright another type of intrarenal AKI is glomerulonephritis, or GN, which means inflammation of the glomerulus. GN is often caused by antigen-antibody complexes depositing in the glomerular tissue.
This deposition activates the complement system, which is a cascade of enzymes that attracts other immune cells like macrophages and neutrophils to the site, which release lysosomal enzymes, causing inflammation and damaging the podocytes, which are the cells that line the glomerulus.
These normally have small gaps between them and have a negative electrical charge, both of which prevents large molecules from filtering through.
When damaged, therefore, membrane permeability increases and large molecules are allowed to be filtered into the urine proteins, called proteinuria, and even red blood cells, called hematuria.
Also this fluid leakage reduces the pressure difference that drives filtration of small molecules and electrolytes like sodium, and so the GFR actually goes down because of the leakage.
Lower GFR means less blood gets filtered and so less urine’s produced, causing oliguria, and that also means more fluid circulating in the blood, which leads to edema or fluid buildup in the tissues, as well as hypertension from excess fluid volume.
Finally, if those nitrogen-containing compounds aren’t being filtered out, more stays in the blood, which causes azotemia.
Alright, finally we have damage to the kidney interstitium as a cause of intrarenal AKI, one key example being acute interstitial nephritis, which is inflammation of the interstitium over the course of days to weeks.
This inflammation is caused by infiltration of immune cells, like neutrophils and eosinophils, which then cause inflammation.
This is thought to be a type I or type IV hypersensitivity reaction, and is typically a response to a medication like NSAIDs, penicillin, and diuretics.
Early symptoms include oliguria and eosinophiluria, which is eosinophils in the urine, but also general symptoms like a fever and a rash.
These symptoms usually subside if the medication is stopped. But if the medication isn’t removed, and the immune cells continue to damage the connective tissue in the interstitium, and those kidney cells can start to die off, called renal papillary necrosis, where the renal papillae are destroyed.
This can again cause hematuria, blood in the urine, as well as flank pain. Other potential causes of renal papillary necrosis are chronic use of analgesics, like aspirin, as well as diabetes mellitus, sickle cell disease, and pyelonephritis.
In general, with intrarenal AKI, the kidneys lose the ability to filter the blood properly, and the cells are often damaged such that reabsorption and secretion are impaired.
If the urea isn’t reabsorbed, less urea stays in the blood relative to creatinine, and the BUN:Cr ratio falls to less than 15 to 1.
Also, those cells can’t reabsorb sodium, meaning the urine Na+ goes above 40 mEq/L, and the FENa, which is the fraction of sodium excreted in the urine, of total sodium filtered, expressed as a percentage, goes above 2%, and finally since water’s not being reabsorbed as much, urine osmolality falls below 350 mOsm/kg.
So as a quick recap, intrarenal AKI is kidney injury caused by something within the kidneys themselves, which could be the tubules as in acute tubular necrosis, the glomerulus as in glomerulonephritis, or the interstitium as in acute interstitial nephritis.
Now that you know all about intrarenal AKI, check out these other two videos on prerenal AKI and postrenal AKI! Thanks for watching, you can help support us by donating on patreon, or subscribing to our channel, or telling your friends about us on social media.