When you (or loved ones) are taking prescription or over the 
counter medications...there is a lot you should be worried 
about, and a lot that your pharmacist may not be telling you.

Most people are aware, for example, that several medications 
taken together can sometimes cause harmful interactions.  Most 
also know that drug allergies can pose significant hazards.  
(These are topics of other articles in this series).  And, many 
people know that young children, elderly adults, pregnant women, 
nursing women, and severely debilitated people may all be at 
higher risk for adverse drug events.

But what most people don't know is that a simple blood test can 
be one of the most important pieces of information in determining 
the correct dose of many medications...and the results of that 
test are almost never available to your pharmacist, especially if
your pharmacist fills your prescription in a retail drugstore.  
(And, that's a bummer.)

The test I'm talking about, of course, is the "serum creatinine 
test" ("SEAR-'em cree-AT-tuh-neen tehst".  It's a difficult 
name to pronounce and a difficult test to understand...but one 
that you NEED to know about if you or loved ones are taking 
over-the-counter or prescription medications.)

A serum creatinine test gives a physician or pharmacist an 
estimate of kidney function.

Serum creatinine is the "bean counter" of modern medicine... 
letting folks know if the beans (the kidneys) are working as 
well as they should.

Why is that important?

Well, kidney function is extremely important in determining the 
correct doses of many medications since the kidneys (along with 
the liver) assist in the removal of medications from the body.

Almost all medications (and/or their chemical by-products) are 
either removed by the liver, by the kidneys, or, in many cases, 
by both the kidneys and liver working together.

So, simply put, when the beans are not working well, many 
medications will accumulate in the body and increase the risk 
of drug side effects.  And that's an even bigger bummer.  (The 
same is true for liver problems, and we will talk about that 
in another article in this series.)

As a result, patients with reduced kidney function often need 
LOWER doses of many medications.

So how does this all work?

Well, creatinine is a chemical that occurs and circulates 
naturally in the human body.  It is the result of normal protein 
break-down.  And, like many medications, creatinine is normally 
removed from the blood by the beans.  So, when the kidneys are 
not working well, the level of creatinine circulating in the 
bloodstream will start to go up...just like the blood level of 
many medications.

Physicians and pharmacists are routinely and easily able to 
determine how much creatinine is in the blood with the results 
of a serum creatinine test. (This test is part of a very common 
panel of blood tests.  And, if the serum creatinine is high, 
many drugs need to have a lower dose.)  The normal value for 
serum creatinine is about 0.4 to 1.5 mg/dl...but that can vary 
a bit from lab to lab.

So remember:  "kidneys no work...serum creatinine go UP".

Now, serum creatinine is not the best measure of kidney function 
(there are other tests that are much more accurate), but results 
of the serum creatinine test are usually the most readily 
available...and cheapest...and are generally accurate enough for 
most purposes...so serum creatinine is the de facto standard for 
estimating kidney function...most of the time.

The gold standard test that doctors use for measuring kidney 
function is called "creatinine clearance" (cree-AT-tuh-neeeen 
CLEAR-uhhh-nce)  However, not many patients get this particular 
test because it is pretty darn inconvenient...and smelly.  You 
have to collect all of your urine for 24 hours and keep it in 
the fridge.  Not a lot of volunteers for this test...

Creatinine clearance is the volume of blood that the kidneys 
clear of creatinine in a given amount of time (and it is 
usually reported as milliliters per minute). 

So, when kidney function decreases, creatinine clearance (the 
amount of blood that the kidneys are successfully "cleaning") 
also decreases.

So remember:  "kidneys no work...creatinine clearance go DOWN".  
(Note: this is easy to remember because it is the exact opposite 
of what you were initially thinking, and the opposite of what 
happens with serum creatinine.  Most of medicine is like this.)

Now for the super tricky part just for those gunning for an A.  
There is a way to "guestimate" creatinine clearance using serum 
creatinine...isn't that neat.  And, that's probably the best way 
to determine renal function if a measured creatinine clearance 
is not available.

What you do is run the serum creatinine value through a fancy 
equation that will give you an estimated creatinine clearance, 
which is itself an estimate of kidney function.  (Estimates of 
estimates of estimates...that's the kind of exacting science I 
live for.)

For adults, that equation is the famous "Cockcroft-Gault 
equation corrected for ideal body weight and gender"...the 
equation everyone loves to hate.  The Cockcroft-Gault equation 
(presumably named after Drs. Cockcroft and Gault...or maybe 
just Dr. Cockroft-Gault, or maybe Lara Croft), is generally 
considered very reliable since it has never been well 
validated in young patients, old patients, thin patients, 
fat patients...basically all the patients it gets used on.  
So go figure.  Double bonus points if you can remember this:

For men, creatinine clearance =

   ((140- Age) * IBW) / (72 * SCr)

For women, creatinine clearance = 

   ((140- Age) * IBW * 0.85) / (72 * SCr)

Where Age is in years, IBW is ideal body weight in kilograms, 
and SCr is serum creatinine in mg/dl.

(For the algebraically-challenged and for anyone wanting help in 
calculating the results of these complicated equations, please 
visit this creatinine clearance calculator:
http://www.medicationadvisor.com/creatinine/creatinine.asp)

Now once you run this a few times, you'll find that creatinine 
clearance for young healthy people is about 100 ml/min (we'll 
just leave off the "ml/min" part from now on).

And, dead people have a creatinine clearance of about 0, 
depending on how healthy they are.

Everyone else falls somewhere in between.

(Now someone in the back of the room is saying, "I just ran 
this on myself and I have a creatinine clearance of 150".  Well 
aren't you special?  In fact, young good-looking people can have 
creatinine clearances of 130, 140, or more...but it doesn't do 
a whole lot of good since 100 is perfectly acceptable.  In fact, 
it's just another case of overachiever overkill.)

Now, if someone has a creatinine clearance of 80, that means 
that they have about...80% kidney function.

And, if someone has a creatinine clearance of 50, that means 
that they have about...50% kidney function.  (Are you following 
all of this?)

Many drugs that are eliminated by the kidney will require 
moderate dosage reductions once a patient's renal function 
is in the 40-60 range.

Patients in the 20-40 range will typically require very large 
reductions in dose.

And, patients who are in the "less than 20" range will often 
need HUGE dosage reductions for medications eliminated by the 
kidney (or better yet, they'll need to take medications that are 
removed by some other organ altogether...if such an alternative 
is available).

One last tidbit to consider.  Renal function declines as people 
age.  No getting around that.  But, the rate of decline is 
different for different people.  By the time you're 50 years 
old, there is a reasonable chance you'll have moderate renal 
function (or worse)...by the time you're 80, you'll almost 
certainly have some important degree of renal impairment...
and you probably won't even know it or feel it.

Now that you know more renal physiology than you ever, EVER 
wanted to know...let's get back to the main thread of this 
article...medication safety.

If you (or a loved one) are at risk for having decreased kidney 
function (and I'll tell you who such folks are in just a second),
you need to step up to the plate and get a handle on this issue 
(because there is a very good chance that your physician and 
pharmacist either didn't have renal function data or didn't 
consider it when coming up with a dosage for you).

Here are the steps I recommend for everyone taking prescription 
or over-the-counter medications:

1) For everyone:  If you have access to the results of a recent 
   serum creatinine test (it is probably part of your annual 
   physical and you may have gotten a copy), memorize it or write 
   it down and then say to your physician or pharmacist when you 
   get a medication, "Say, I think my serum creatinine is about 
   X. So, does this medication need any dosage adjustment in 
   order to be safe for me?

2) If you are in one of the following categories, you should 
   expect your physician and pharmacist to have considered 
   your renal function before dosing a medication:

   * known kidney disease;
   * age greater than 50;
   * history or heart attack, angina, stroke, or other artery 
     blockages;
   * history of diabetes (any type);
   * history of high blood pressure;
   * prior exposure to chemotherapy drugs;
   * prior prolonged exposure to IV antibiotics;  
   * frequent use of pain medications (especially non-steroidal 
     anti-inflammatory drugs, but others as well).

   So you might say to your physician or pharmacist, "Is this 
   drug removed by the kidney, because I have condition X that 
   could decrease kidney function and I just want to be safe."  
   If the drug is removed by the kidney, you might also ask the 
   physician or pharmacist to tell you what your serum creatinine 
   is...and if he or she does not have this information, a big 
   red flag should be going up in your head.

3) If you are not in one of the categories in question 2 and you 
   don't have a serum creatinine available, don't worry.  You're 
   probably safe.  But you may want to ask your physician if 
   there is a serum creatinine in your chart and if so, what 
   it is.

4) If you are on dialysis of any sort, serum creatinine is not 
   all that useful for dosing medications.  Just make sure your 
   physician and pharmacist are aware that you are on dialysis 
   and perhaps ask, "Now is this the usual dose for someone on 
   dialysis?"

These are some of the steps I hope you will consider the next 
time you get a prescription or over-the-counter medication so 
you can be sure that that you (or your loved one) are getting 
the right dose.



© 2004 Timothy McNamara, MD, MPH