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Sources of error of the Cockcroft-Gault equation: How to adjust a CLcr or GFR ?

Sources of error of the Cockcroft-Gault equation: How to adjust a CLcr or GFR ?
Let’s consider some of the sources of error of the Cockcroft-Gault equation. By the way, these errors that were gonna be talking about do not apply to the urine collection method. First is body weight, remember we mentioned that the study population of the Cockcroft-Gault study was not obese. They were a reasonably normal body weight. And much of patient populations today include obese patients, so there is a concern. And that concern is based on the fact that adipose tissue, fat tissue does not produce creatinine. Creatinine is produced by metabolizing muscle tissue. So if a patient has an abnormal amount of adipose tissue, then a significant portion of their body weight is not related to producing creatinine.
And it’s disproportionate most likely in relation to the study population that produced the Cockcroft-Gault equation. What’s been shown in studies is that for obese patients, when using actual body weight, the Cockcroft-Gault equation tends to overestimate creatinine clearance. But when using ideal body weight which ignores the adipose tissue, the Cockcroft-Gault equation tends to underestimate creatinine clearance. So what some clinicians have suggested doing and then this is standard practice in many institutions is to use an adjusted body weight in which 40% of the difference between the actual body weight and the ideal body weight, is then added back to the ideal body weight to develop what we call as a the adjusted weight.
it’s somewhere between patients actual body weight and ideal body weight. And it’s found that when you use that adjusted body weight in the Cockcroft-Gault equation, it tends to give a more accurate value than using either actual body weight or ideal body weight. Muscle mass is also a consideration. When the patient has particularly low muscle mass, hectic patient, a very elderly patient, patients that are malnourished, or it can even involve paralysis, in which the amount of metabolizing muscle tissue that the patient has is very low. And since creatinine is produced by metabolizing muscle tissue, those patients will produce an abnormally low amount of creatinine. Now this causes their serum creatinine to be a falsely low indicator, a renal function.
In other words, they may have a fairly low serum creatinine value. Not because their kidneys are function abnormally, but simply because they’re not producing a normal amount of creatinine. And this can skew the results of creatinine clearance estimation. So a low serum creatinine concentration will result in an overestimation of creatinine clearance. And this also affects the MDRD and the CKD-EPI equation, they are not impacted significantly by obesity. But since they do include serum creatinine in their linear regression analysis, they can give an erroneously elevated or over estimated GFR prediction when a patient has very low serum creatinine because they have low muscle mass or they are paralyzed.
One practice that’s been used by clinicians is to arbitrarily round up a certain creatinine value. If it’s below 1.0 or 0.8 to round it up to one of those values. However, that practice is not well supported in studies if a patient has a very low serum creatinine because they have a very low muscle mass. Let’s say they have a value of 0.4 or 0.6
Rounding up to 1.0 or 0.8, might be a little bit more accurate than actually using the 0.4 or 0.6. But it’s still an arbitrary value. Some patients the rounding off to 1.0 or 0.8 might be better, but for any individual patient, the studies have shown that that’s not a reliable method. However, the one thing that you can say for certain is that when a patient has a very low muscle mass. The low serum creatinine value is misleading, and it has to be taken with a grain of salt when you estimate creatinine clearance using a low serum creating value in such a patient.
Take a moment to answer this question, and then we’ll discuss the answer.
When using the CockCroft-Gault equation to estimate creatinine clearance, the first statement A is true. Some creatinine will be falsely low if the patient has low muscle mass. We indicated creatinine is produced by metabolizing muscle tissue. So if a patient doesn’t have much muscle tissue, they won’t be producing very much won’t be producing much creatinine and therefore their serum creatinine will be low. Statement B is false. Creatinine clearance will be falsely low if the patient has low muscle mass. Their serum creatinine is what will be falsely low, if the patient has low muscle mass. The creatinine clearance which is inversely related to serum creatinine will be falsely elevated or overestimated if the patient has low muscle mass.
And statement C is also false. Serum creatinine will be falsely low if the patient is obese. If the patient is obese, serum creatinine is not significantly impacted. It’s a function of whether or not the patient has a normal muscle mass, if the patient has excess adipose tissue that doesn’t change the fact that they have a normal muscle mass, and would be producing a normal quantity of creatinine. So the answer to this question is A. Let’s consider the process of adjusting a patient’s creatinine clearance or GFR to body size. This would be to a body size of 1.73 meters squared, or to 70 kilograms. The CockCroft-Gault equation produces a result that is not correct.
It’s simply in milliliters per minute whereas the MDRD and the CKD-EPI equations produce a value of GFR that is already adjusted to 1.73 meters squared. Now, the point here is that if a patient is much larger than 1.7 3 meters squared, a creatinine clearance of 100 milliliters per minute which for a patient with normal body size would be a normal value might be insufficient if they’re significantly larger than 1.7 3 meters squared. And likewise, if a patient is very small, much smaller than 1.73 meters squared, a creatinine clearance of 50 milliliters might be normal for that body size.
By equating the patient’s creatinine clearance to a standard body size such as 1.7 3 meters squared, it facilitates comparing the patient’s creatinine clearance to a standard range. Typically a range of about a hundred to 140 milliliters per minute for creatinine clearance is considered normal, but it’s a better representation of comparison to a normal range if the patient’s value is corrected to 1.73 meters squared. It’s comparing apples to apples rather than apples to oranges if a patient has a different body size. What’s normally done is simply to take the patient’s creatinine clearance in milliliters per minute, and multiply if we’re going to equate it to 1.73 meters squared. Multiply it by 1.73 meters squared over the patient’s body surface area.
And that yields a value with the unit’s milliliters per minute per 1.73 meters squared. As an alternative, the patient’s creatinine clearance can be equated to a body size of 70 kilograms, in which case the value for creatinine clearance will be multiplied by 70 divided by their actual body weight. And that would produce creatinine clearance value with the units milliliters per minute per 70 kilograms.
What’s critical in terms of using adjusted or sometimes corrected or normalized creatinine clearance value to 1.73 meters squared or for 70 kilograms. What’s really critical here is to make sure that the units that are being compared are the same. Now, it may be that a particular drug and renal studies done with the Cockcroft-Gault equation, and so the dosing recommendations for patients with renal impairment are based on an uncorrected creatinine clearance that’s not adjusted to a normal body size.
Now, if the patient has an MDRD estimation of their GFR which is corrected to 1.73 meters squared, it would not be appropriate to compare that value to a set of dosing guidelines using the Cockcroft-Gault equation in which the creatinine clearance values were not corrected to body size. So, it’s important to make sure that the units match, whatever value the patient’s creatinine clearance or GFR is estimated in those same units should be related to the dosing guideline, that were produced using either milliliters per minute or milliliters per 1.37 meters squared. It’s important simply to make sure you’re consistent.

In this part, we can learn two sources of error: body weight, and very low muscle mass (or paralysis).

We need to know how to adjust a patient’s creatinine clearance (CLcr) and GFR based on the type of error.

Make sure that the units match and you’re consistent.

What is the difference between actual and corrected CLcr (GFR)? Leave your answer below and feel free to share any question you may have!


Prof. Daniel L. Brown

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Clinical Pharmacokinetics: Dosing and Monitoring

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