Use of Newer Anticoagulants in Patients With Chronic Kidney Disease

Bob L. Lobo


Am J Health Syst Pharm. 2007;64(19):2017-2026. 

In This Article

Quantification of Kidney Function and the Prevalence of Renal Impairment

Kidney function should generally be evaluated in all patients commencing anticoagulant therapy, and the American College of Chest Physicians (ACCP) recommends that renal impairment be considered when dosing anticoagulants cleared by the kidneys, especially in elderly patients or patients at high risk for bleeding.[1,2] The glomerular filtration rate (GFR) is currently accepted as the best measure of overall kidney function.[6] Clinical practice guidelines for the classification of CKD based on kidney function have been established by the Kidney Disease Outcomes Quality Initiative group of the National Kidney Foundation.[6] These guidelines stratify CKD into five stages on the basis of GFR estimates ( Table 1 ). The overall frequency of CKD in U.S. adults has been estimated at 11%, or approximately 19.2 million people.[7] Approximately 3.3% of adults in the United States have stage 1 CKD, 3.0% have stage 2 CKD, 4.3% have stage 3 CKD, and 0.4% have stage 4 or 5 CKD. The prevalence of CKD is higher among hypertensive and diabetic adults and increases with age in the general population.[7] Approximately 11% of all adults older than 65 years without hypertension or diabetes have stage 3-5 CKD.[7] In this population, decreases in GFR often occur without markers of kidney damage.[6] Chronic decreases in GFR without kidney damage may also be seen in adults with extracellular fluid depletion or systemic illnesses associated with reduced renal perfusion.[6]

The Cockcroft-Gault formula[1] and Modification of Diet in Renal Disease (MDRD) equation[8] are the most commonly used methods to estimate GFR in clinical practice. These formulas estimate GFR based on serum creatinine (SCr) concentration in combination with other variables, such as age and sex.[1,8] The MDRD equation was originally developed and validated in a large population of patients with CKD and has since been evaluated in numerous sub-populations of patients with kidney disease.[8] The MDRD equation is generally considered to be more accurate than the Cockcroft-Gault formula, which overestimates the GFR.[1,8] It is currently recommended that the MDRD equation should be used to determine the stage of CKD but should not be used for dosing medications.[8,9] Data related to the dosing of newer anticoagulants in patients with renal impairment were derived using the Cockcroft-Gault formula.[8] In clinical practice, use of the MDRD equation may result in a lower estimated GFR compared with the Cockcroft-Gault equation. This may lead to dosage reductions in patients with higher GFRs than the manufacturer intended and the potential for underdosing the patient. Until there are more dosing data based on the MDRD equation, clinicians should exercise caution when applying this equation to adjust dosages of newer anticoagulants in patients with renal impairment.


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