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Estimating Creatinine Clearance in the Elderly: To Round or Not to Round?


Question:
When estimating renal function, should creatinine be rounded upward in elderly patients with low serum creatinine?
Response from Michael J. Postelnick, BSPharm
Lecturer, Department of Family and Community Medicine, Northwestern University School of Medicine; Senior Infectious Diseases Pharmacist; Manager, Research and Education, Department of Pharmacy, Northwestern Memorial Hospital, Chicago, Illinois
An accurate estimate of a patient's glomerular filtration rate (GFR) is a critical element in the safe and effective dosing of renally eliminated medications. Serum creatinine, which is an endogenous marker of glomerular filtration, is commonly used to help estimate the GFR. The GFR estimate is most commonly derived using 1 of 3 equations: the Cockcroft-Gault,[1] the modification of diet in renal disease (MDRD),[2] or the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI).[3]
The MDRD and CKD-EPI equations estimate the GFR directly, whereas the Cockcroft-Gault equation estimates creatinine clearance (CrCl). While CrCl is the parameter most often used in clinical trials to determine dose adjustments for renally eliminated medications, the National Kidney Disease Education Program recommends that either Cockcroft-Gault or MDRD be used to determine drug dosage adjustments.[4] No comment is provided in this recommendation regarding application to the elderly population.
GFR declines with age, even in the absence of chronic kidney disease, from an average of 116 mL/min/1.73 m2 at age 20 to about 75 mL/min/1.73 m2 at age 70.[4] This natural decline is accounted for in the 3 estimating equations. However, both muscle mass and dietary intake can affect creatinine generation and subsequent creatinine measurements. Lower than normal muscle mass and decreased dietary protein intake, both situations that are somewhat common in the elderly, can result in falsely depressed serum creatinine levels. In order to avoid the potential overestimation of GFR or CrCl that may result from these falsely low creatinine values, some pharmacists have routinely advocated rounding low serum creatinine values to 1 mg/dL in the elderly. However, when systematically reviewed, routine employment of this practice has actually been associated with greater potential dosing error.
Smythe and colleagues[5] evaluated the use of rounded serum creatinine values to determine aminoglycoside dosing in elderly patients. These investigators found that routine rounding to 1 mg/dL resulted in a significant underestimation of required aminoglycoside dose. In a meta-analysis of 13 trials including a total of 1197 patients, Wilhelm and Kale-Pradhan[6] found that, based upon their analysis, they were unable to recommend routine rounding of serum creatinine values to 1 mg/dL. Finally, recent data presented by Dowling[7] at the 2011 American College of Clinical Pharmacy meeting demonstrated a significant risk of underdosing of elderly patients when low serum creatinines were routinely rounded to 1 mg/dL. These data all demonstrate the risk associated with routine rounding.
To avoid these types of systematic errors when dosing medications using estimates of renal function based upon serum creatinine, one must be aware of the aforementioned factors that impact production of this endogenous biomarker. When critical drug dosing decisions are being made, rather than adopting a general rule, each patient should be assessed individually to evaluate the reliability of the measured creatinine value as an indicator of renal function.
Laboratory markers such as albumin can offer a crude assessment of nutritional status. There are a number of potential causes for a low albumin, but the nutritional status and subsequent ability to produce creatinine at a normal rate should be immediately suspect in patients with a low serum albumin. Actual visual assessment of the patient is often the best way to determine muscle mass status. If muscle mass is assessed as near the norms for the patient's age, the actual creatinine value should be used in estimating the patient's renal function.
If muscle mass is likely below normal, the pharmacist should utilize clinical judgment, assessing the clinical status of the patient, therapeutic index of the medication to be administered, severity of the patient's illness, and the consequences of underdosing vs overdosing in designing an appropriate dosing regimen for the patient. The need for this type of careful assessment precludes the development of a general "rule" that can be applied in all situations.

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