The Family Practice Newsletter
The Ohio University College of Osteopathic Medicine
The Ohio Northern University Raabe College of Pharmacy
Doctors Hospital Family Practice
Volume 6, Issue 3
October, 2006
Estimated Glomerular Filtration Rate or Creatinine Clearance: Which method should be used when
adjusting medications for patients with renal dysfunction?
Mike Moranville, ONU Doctor of Pharmacy Candidate
Drugs that are eliminated primarily by the kidneys require dosage adjustment for patients who have renal
dysfunction. Without appropriate adjustment, these patients will experience higher than normal concentrations of drug in their
body, leading to adverse events and toxicity. Serum creatinine is the most common physiologic marker used to determine a
patient’s kidney function. Creatinine clearance (CrCl) and estimated glomerular filtration rate (eGFR) are the most common
methods to evaluate renal function. When patients are renally compromised, dosage adjustment must be made. Which method
should be used when determining renal function and appropriate medication dosage: eGFR or CrCl?
Creatinine is filtered by the kidneys, but it is also reabsorbed and secreted in the renal tubules. Therefore, changes
in the SrCr value can be helpful in determining renal function. Normal serum creatinine (SrCr) values can range between 0.71.5mg/dL, depending on age and gender.2 Females and elderly patients tend to have lower SrCr values, when compared to
otherwise healthy males. Malnourished patients and patients with amputations also have lower creatinine levels. Adversely,
some medications can cause the SrCr values to be falsely elevated, including certain antihypertensive medications,
trimethoprim, cimetidine, and fibric acid derivatives (other than gemfibrozil). Keto acids and some cephalosporins can also
interfere with assays and show increased levels. SrCr may also be falsely elevated in active, muscular individuals without renal
impairment. It is important to consider the condition of the patient when making a final evaluation of his renal function.1-3
Creatinine clearance(CrCl) is an estimate of GFR by factoring age, weight, and gender. There are many equations
used to calculate CrCl. However, when assessing renal function for the purpose of appropriately dosing medications, the
Cockcroft-Gault equation is the most common equation used. The Cockcroft-Gault equation is listed below:
CrCl = {[(140-age) x IBW]/[72(serum creatinine)]}x (0.85 if female)
Ideal body weight (IBW) is reported in kilograms, age is in years, and SrCr is in mg/dL. Creatinine must be at a steady state
concentration to accurately evaluate renal function, and it takes longer to reach steady state with renal impairment. 2
The CrCl overestimates GFR due to the fact that creatinine is also secreted in the proximal tubule.1
Measurements of CrCl can be skewed in specific groups of patients including the elderly, patients with hypoalbuminemia,
chronic renal insufficiency, a serum creatinine less than 1.0mg/dL, obese patients, and diabetes mellitus patients.6
GFR is more accurate and is the best marker of kidney function. Normal GFR in young, healthy individuals is
120mL/min/1.73m2 and is impacted by age, gender, and body surface area. 1,3 Exogenous substances (inulin, iothalamate,
iohexol, and radioactive substances) and 24-hour urine collection must be done to accurately measure GFR. 1-3 Creatinine can
be used with other factors (age, gender, and race) to estimate GFR from the abbreviated Modification of Diet in Renal Disease
(MDRD). This equation is similar to the original MDRD, but does not incorporate albumin and blood urea nitrogen because
these substances are more cumbersome to measure. The National Kidney Foundation supports use of the abbreviated MDRD
to measure GFR (GFR (mL/min/1.73m2) = 186 x (plasma serum creatinine)-1.154 x (age)-0.0203 x (0.742 if female) x (1.210 if
black)).1,3 This equation underestimates the GFR in healthy patients because it was developed in a study of patients with
chronic kidney disease. It is more accurate in patients with higher serum creatinine levels. 3,5
Creatinine clearance provides better response for pharmacokinetic dosing because most studies use this
measurement when evaluating kinetic parameters in order to estimate drug clearance and determine dose adjustments.2 The
National Kidney Foundation considers GFR estimates to be accurate and safe for clinical decision making if the method used is
within 30 percent of the measured GFR. Several studies have compared different methods for estimating GFR from the
Cockcroft-Gault equation and evaluated their accuracies. Using the Cockcroft-Gault equation without any adjustments in
weight or body surface area (detailed above) showed a high correlation with the MDRD equation and was within 30 percent of
the measured GFR 72 percent of the time.4,5
Created and Edited by: Stephanie Gibson, PharmD, RPh.
Assistant Clinical Professor, ONU Raabe College of Pharmacy
Director of Clinical Pharmacy Services, Doctors Hospital Family Practice.
Questions and/or comments: sgibson@ohiohealth.com
As there are flaws and inaccuracies associated with creatinine clearance equations for using both methods, it is
important to determine which method to use when dosing medications. GFR does report a more accurate evaluation of kidney
function in some patients; however, CrCl was the method used by manufacturers in developing dosage adjustments. If used
inappropriately, patients may be exposed to too much or not enough medication to properly treat the indication. To avoid these
situations, CrCl should be calculated and the appropriate dose of medication should be chosen based upon that result.
References:
1. O’Mara NB. Calculating renal function. Pharmacist’s Letter/Prescriber’s Letter 2005; 21(7):
210704.
2. Traub SL, ed. Basic Skills in Interpreting Laboratory Data. 2nd ed. Bethesda, MD: American Society of Health-System Pharmacists; 1996: 132-141.
3. National Kidney Foundation. Frequently Asked Questions about GFR Estimates. 2004 [cited 25
September 2006]. Available from: URL: http://www.kidney.org/kls/patients/faq.cfm.
4. Rosborough TK, Shepherd MF, Couch PL. Selecting an equation to estimate glomerular filtration
rate for use in renal dosage adjustment of drugs in electronic patient record systems.
Pharmacotherapy 2005; 25(6): 823-830.
5. Rule AD, Larson TS, Bergstralh EJ, Slezak JM, Jacobsen SJ, et al. Using serum creatinine to
estimate glomerular filtration rate: Accuracy in good health and in chronic kidney disease. Ann
Intern Med 2004; 141: 929-937.
6. Spinler SA, Nawarskas JJ, Boyce EG, Connors JE, Charland SL, et al. Predictive performance of ten
equations for estimating creatinine clearance in cardiac patients. Ann Pharmacother 1998; 32: 12751283.
Questions from your patient…..
Due to the severe microvascular and macrovascular complications that result from uncontrolled diabetes mellitus
(DM), physicians and patients are searching for ways to decrease blood glucose levels. Though exercise and weight loss
are known to improve glycemic control, not all patients are willing to take medical advice and increase physical activity
leading to weight loss. Prescription medications lower hemoglobin A1c values in the range of 0.5-1.5%, depending on the
agent.3 However, this may not be enough to get the patient to goal A1c of <7-6.5%. When this happens, some patients will
take the initiative and ask questions regarding non-prescription drug methods to improve their glycemic control—
sometimes turning to natural products. Cinnamon is one of the natural products being used to assist patients in improving
their glycemic control.
Kahn and colleagues evaluated the effect of cinnamon on glucose and lipids in patients with diabetes. 1 In this
study (n=60), patients were randomized to receive either 1.) 500mg cinnamon cassia twice a day 2.) 1g three times a day
or 3.) 2g three times a day or 4.) placebo. During the study, blood glucose, triglyceride, and cholesterol levels were
measured at baseline, and on days 20, 40, and 60. The results of this study showed that cinnamon decreased serum glucose
levels, ranging from 18-29%. Decreases of serum triglyceride levels were also observed, ranging from 23-30%.
Improvements in LDL, total, and HDL cholesterol were also observed. There were no relationships between dosage of
cinnamon cassia and reduction in values among the groups.
From this study, we are able to conclude that cinnamon cassia may have a beneficial effect on the measured
metabolic parameters, including blood glucose.1 When discussing this with patients, it is important to note the specific type
of cinnamon used, because not all cinnamon products have been studied and therefore may not have this beneficial effect
on blood glucose levels. The amount of cinnamon found to be useful in the study equates to approximately one-half
teaspoonful per day.2 Or, if patients are able to obtain cinnamon cassia capsules/tablets, recommend they start at 1 gram
daily. Remind them of the importance of continued self-monitoring of their blood glucose, so that we can monitor the
effectiveness of they cinnamon product and avoid any hypoglycemic episodes as they are still at risk.
References:
1. Khan A, Safdar M, Ali Kahn MM, et al. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care 2003;26:32153218.
2. Cinnamon for Patients with Type 2 Diabetes. Pharmacist’s Letter/Prescriber’s Letter 2004;20: 200813.
3.
Nathan DM, Buse JB, Davidson MB, Heine RJ, Holman RR, Sherwin B, et. al. Management of hyperglycemia in type 2 diabetes:
a consensus algorithm for the initiation and adjustment of therapy. Diabetes Care 2006; 29(8): 1963-1972.
Created and Edited by: Stephanie Gibson, PharmD, RPh. Assistant Clinical Professor, ONU Raabe College of Pharmacy
and Director of Clinical Pharmacy Services, Doctors Hospital Family Practice.
Questions and/or comments: sgibson@ohiohealth.com
Created and Edited by: Stephanie Gibson, PharmD, RPh.
Assistant Clinical Professor, ONU Raabe College of Pharmacy
Director of Clinical Pharmacy Services, Doctors Hospital Family Practice.
Questions and/or comments: sgibson@ohiohealth.com