Pharmacists and Authorized Drug Prescribers

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:

1. 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. 
2. 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. 
3. 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.
4. 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.
5. 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). 
6. 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. 
7. 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.