How are your kidneys doing? Pissing good? Let’s discuss: Kidney Function

Who's on the field?
BUN (Blood Urea Nitrogen) – A metabolic waste product created when the body breaks down protein. Eat a steak, produce this. You piss it out.
Creatinine Serum – Another metabolic waste product, this of muscle metabolism. It is also supposed to get pissed out. It’s the waste byproduct of the use of creatine, which for those in the know is a popular bodybuilding supplement, taken on the premise that giving muscle more of the component it needs to build will improve its capacity to do so. This is true to a degree, and only if you actually make the muscle need to consume the creatine. Taking it and sitting on your ass does nothing.
BUN/Creatinine Ratio – The ratio of the two above. This number is simply the lab doing math for you.
Glomerular Filtration Rate – This is the thing in the kidneys that’s supposed to be letting the BUN and creatinine out of the door. Your GFR on a blood test is actually calculated based on your creatinine with other factors, such as age, gender, and race considered, so it’s not a reading in and of itself, but uses other readings to give basically an estimate of your kidneys’ ability to process blood. In my case, my kidneys are cleaning out 120-odd milliliters of blood every minute. (Obviously, this is different from producing 120 milliliters of urine. That would suck because you’d never stop peeing.)

What do you need to know about the kidneys for this to make sense?
Not much. The important structures here are the glomerulus and the renal tubules. Think of the glomerulus as a strainer; if it’s larger than a red blood cell, it doesn’t get through. Negatively charged smaller proteins (such as albumin) also don’t pass through due to a membrane in the glomerulus that repels them. (NERD ALERT: Small negatively charged anions such as chloride do pass through this membrane, since the cells aren’t close together enough to repel such small blood components.) In other words, a whole lot of stuff you don’t want to piss out passes through here. The renal tubules come after this; these tubes run closely to blood vessels to allow for reabsorption by various means along the tubes. At different points along the tube, diffusion, osmosis, and active transport all conspire to retain things the blood needs to keep. Keep in mind that this filtration system relies on material only spending so long within it—filtration pressure, as such, is important. Also, drugs and hormones that influence the retention and excretion of water, sodium, and a billion other things, mostly all act on these tubules. Knowing the difference between these two things is important becaaause…

BUN and creatinine are used together because while both indicate that you’re not getting rid of waste, the two in conjunction tell you where the problem is, and whether the insult is at the glomerulus or in the tubules or elsewhere. BUN and creatinine both filter through the glomerulus normally. They’re different in that creatinine does not get reabsorbed later in the tubules, while some BUN does get pulled back into the blood. The other key difference is that BUN levels are influenced by short term behaviors such as your diet, where creatinine level is determined by how much muscle you have, and so doesn’t change quickly. Your BUN goes up if you eat a steak, but your creatinine will only increase if you pack on a significant amount of muscle, which takes longer.

What does this mean? Any situation where the creatinine is abnormally high is indicative of kidney problems in glomerulus. If the BUN is also elevated, but in proportion to the creatinine (high levels of both with a normal ratio), the problem is postrenal, or after the kidneys; it’s an obstruction of some kind in the urinary tract, such as kidney stones or severe enlarged prostate. Blockage past the kidneys causes the urine produced to back up, leading to what’s called hydronephrosis, where the kidneys become distended with fluid and the cellular function is destroyed. Think of it as trying to squeeze water through a coffee filter instead of letting it pass on its own—you’ll break the filter eventually.
If they are both high but disproportionately so (low BUN/Cr ratio), it means that the kidney’s not only failing to pass them through the glomerulus as well as it should, but it’s also failing to pull back in some of the BUN; the tubule system that comes after is also shot. A postrenal insult as mentioned in the above paragraph will eventually lead to this, which is intrarenal or intrinsic renal failure. The low BUN/Cr ratio is temporary, however. As the damage progresses, neither BUN nor creatinine will get to the tubule system, which must occur for the ratio to be low.

A high BUN/Cr ratio can indicate many things, however.  Regardless of the ratio, if the creatinine is still normal, kidney damage has not occurred, but many of the reasons for a high Bun:Cr ratio are eventually going to damage the kidney.
If your BUN/Cr ratio is high but you are not diagnosed with kidney failure and you’re in no pain, you’re probably eating too much protein. BUN is the waste product of protein breakdown, so if it’s high, it could simply be that you’re breaking down lots of it, and while your kidneys are handling the normal workload of the creatinine just fine, and you’re throwing more BUN at them than they can rid the body of quickly. Put down the protein shake and the rump roast, you stupid gym-rat. (This excess of BUN produced by eating protein is the reason that people with kidney failure, including those on dialysis, eat low-protein diets. This is about the only situation ever where such a diet is promoted.)
Oh? BUN/Cr ratio is high and you don’t eat ten steaks and a pound of whey powder a day? Well remember that creatinine is an indicator of kidney damage. But if the BUN is elevated without any excessive intake of protein, something’s still wrong. Remember what I said about filtration pressure? Both BUN and creatinine are passing through the glomerulus  as they should, but the remaining product isn’t being pushed through the renal tubules where return diffusion of BUN occurs, and while it sits there, more BUN is being diffused into the blood than normal. Dehydration, blood loss, and heart failure are all things that mess with your body’s ability to shove blood into the kidneys to get cleaned out, and they’re all situations where the BUN will rise in proportion to the creatinine. This is bad, because the kidneys are very use-em-or-lose-em. If the blood isn’t reaching the kidneys efficiently enough to get cleaned, it’s also not reaching them efficiently enough to perfuse them, and the filtration system can croak on you if you don’t keep pressure on it. This is often how acute renal failure occurs. Lose a limb, bleed too much, and congrats, not only have you got no leg, but you’re on dialysis. Renal failure, by the way, can occur by the opposite as well—uncontrolled high blood pressure can pound on your kidneys so hard you blow them out. My first patient was a 30 year old on dialysis for the rest of his life because he didn’t take blood pressure medication—in every other respect, he was perfectly healthy. That sucks, and it was completely preventable.

There is another major reason for a high BUN with a normal creatinine (high ratio), based on the same principle of excess protein breakdown, but without anything in your diet to cause that. This is an upper gastrointestinal bleed, especially in the absence of vomiting blood. Why? Think about it—your GI system doesn’t distinguish self from non-self, you fill it with blood and it’s going to process all that yummy protein, whether the blood’s yours or a cow’s. If you’re not vomiting blood, but you’re bleeding into your GI system, you know what’s probably wrong with you? Your pancreas. You sir, probably have pancreatitis and are in more pain than anyone else can imagine because you’re literally digesting your insides. This is most commonly caused by alcoholism or gallstones, which occur more frequently in overweight people. If you present in a hospital with severe abdominal pain, on top of this regular bloodwork, your amylase and lipase levels will be taken. Mine weren’t because they’re only drawn for differential diagnosis, but amylase and lipase are pancreatic enzymes responsible for breaking down the carbs and fats you eat. If they’re elevated in the blood, your pancreas is spilling them, and their ratio can be used to indicate when this began.
For the nerdy House FYI, in a differential diagnosis, if these are normal when you come into the ER with severe abdominal pain, the most likely cause is appendicitis. If you’re a female of childbearing years, your beta-HCG level (more on that later) is also drawn, to rule out an ectopic pregnancy, which presents the same. By the by, your nurse probably drew these labs based on ‘standing orders’, or a doctor’s orders pre-written based on criteria such as abdominal pain. Standing orders are an interesting legal grey area where nurses are given responsibility above and beyond their scope of practice using paper loopholes. That sucks.

In summary, BUN and creatinine are first and foremost about the kidneys. Pancreatitis can also be strongly indicated by them, but the amylase and lipase are what’s important there, and furthermore, no one stumbles across pancreatitis because of its severe symptoms. Kidney function problems can, however, be discovered in labwork before symptoms really become evident. In the case of surgery, making sure your ability to filter waste is good and consistent with your age is important information, especially for the anesthesiologist, who may have to alter his dosages or the drugs he uses based on the efficiency of your kidneys. While most drugs are metabolized in the liver, the kidneys still need to remove the resulting product, or the metabolite, which in some cases is toxic if built up, or has another undesired effect. Some drugs are actually active after the liver processes them for removal, which means if the kidneys don’t filter that product, the drug itself is building up.

As you can see, my BUN, creatinine, their ratio, and consequently my GFR, are all within normal range. In fact they’re like smack dab in the middle. So I guess I don’t need to worry about that. (Interestingly, my protein intake is pretty high compared to the average, which tells you exactly how much of a maniac you have to be to over-consume protein. And yet stupid Ahnald wannabes do this surprisingly often.)

This is pretty interesting, Gio. I love behind the curtain stuff like this—expert knowledge in practical fields. Also, I can never decide whether living beings are ridiculously, insanely freaking complicated or the most elegant machines ever to arise in the universe.

Quick question: you said hyperglycemia damages the capillaries. What affect does hypoglycemia have? Stops the muscles from functioning properly? (Uh, if I could have the answer in "captain dummy-talk," that'd be great. I'm not going to understand anything particularly technical.)

Giovanna wrote:

A hypoglycemic state appears a lot like being drunk as the brain functions less and less at proper capacity: fatigue, a lack of coordination, stupor, impaired judgment, and eventually things like jerky movements and respiratory distress.

You have just described my everyday existence!

Giovanna wrote:

I haven't forgotten the thread but the last two weeks have been brutal for anything like structured thought.

:hugs:

I'm a microbiologist, and I approve of this thread.