Creatinine Standardization Recommendations
Clinical guidelines used by pharmacists and
clinicians to adjust drug dosages for patients with impaired kidney
function are usually based on estimating equations for creatinine
clearance (e.g., Cockcroft-Gault). These estimating equations were
developed using serum creatinine methods that had a positive bias of
about 10 to 20 percent. When laboratories recalibrate serum creatinine
methods to remove that positive bias, a patient's creatinine result
will become lower, in most cases. Conversely, estimates of kidney
function using any of the estimating equations or algorithms derived
from older creatinine methods will become higher by roughly the same
percentage. Depending on the analytical system used by the clinical
laboratory, and how that method calibrates urine creatinine
measurements, the creatinine clearance calculated from serum and urine
measurements either will be unaffected by the recalibration of
creatinine or may increase slightly.
Pharmacists and authorized drug prescribers
should contact their clinical laboratories to determine if they are
using creatinine methods with calibration traceable to isotope dilution
mass spectrometry (IDMS). In turn, NKDEP encourages clinical
laboratories to notify pharmacists and authorized drug prescribers of
the expected magnitude of change in serum creatinine values, and
whether the creatinine clearance measured from serum and urine will be
affected by the change.
Pharmacists and authorized drug prescribers should consider the following:
- Following implementation of revised calibration for serum
creatinine methods, use of the IDMS-traceable Modification of Diet in
Renal Disease (MDRD) Study equation will give a more accurate value for
eGFR in adults.
- The serum creatinine reference interval will change, in most
cases, to lower values. The magnitude of change is likely to be between
5 to 20 percent.
- Creatinine clearance values based on measured serum and urine
creatinine results may change. A new reference interval and
interpretive criteria may need to be established for creatinine
clearance. The effect on measured creatinine clearance will vary
depending on the procedures used to calibrate serum and urine
measurements.
- Following implementation of revised calibration for serum
creatinine methods, creatinine clearance estimating equations such as
Cockcroft-Gault, Schwartz, or Counahan-Barratt will, in most cases,
give values that are higher than those values obtained before
creatinine method recalibration. Guidance for using the Schwartz
equation with creatinine measured by methods that have calibration
traceable to IDMS is available in the GFR Calculators
section. Individual institutions will need to determine the clinical
implications of these higher values. In many instances, the change may
have little clinical significance for drug dose decisions. Institutions
may wish to refer this issue to a multi-disciplinary team (e.g.,
clinical decision support team) to determine the impact of creatinine
calibration changes at their institution.
- For identifying and staging chronic kidney disease (CKD), an
eGFR derived by the MDRD Study equation is more accurate than
creatinine clearance calculated from serum and urine measurements for
most patients. Therefore, NKDEP recommends against performing a
measured creatinine clearance procedure for adults, except when the
patient's basal creatinine production is abnormal. This may be the case
with patients of extreme body size or muscle mass (e.g., obese,
severely malnourished, amputee, paraplegics, or other muscle-wasting
diseases) or with unusual dietary intake (e.g., vegetarian, creatine
supplements).
- For drug-dosing purposes, NKDEP does not recommend using the
MDRD Study equation because the clinical impact on drug-dose adjustment
has not been compared between current practice and the MDRD Study
equation. Pharmacists should continue to use their current drug-dosing
methods, but understand the potential influence of lower creatinine
values from methods that have calibration traceable to an IDMS
reference method.
- Pharmacists should keep in mind that the MDRD Study equation is
an important tool for identifying patients at risk for CKD. These
patients are at high risk for developing drug-related problems.
Utilizing the MDRD Study equation to identify patients at risk for CKD
provides pharmacists an opportunity to collaborate with physicians in
optimizing medical management of these patients.
The NKDEP Laboratory Working Group is collaborating with the American
Society of Health-System Pharmacists to discuss the impact of the above
issues on pharmacists and patient care.
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