In stage-5 CKD patients, the primary route of drug elimination is often the dialysis procedure itself. However, in predialysis CKD patients, dosage adjustments are usually required for renally eliminated drugs. Nearly every marketed drug has had the renal adjustment calculated based on a Cockroft-Gault-derived estimate of creatinine clearance. However, the modification of diet in renal disease (MDRD) equation [25] is now considered a better estimate of GFR. Indeed many institutions have begun routinely calculating the MDRD GFR estimate when laboratory results are reported. It is possible that a dose based on MDRD GFR estimates might be different from Cockroft-Gault-derived doses, however, a clinical study comparing dosing regimens and patient outcomes based on these two techniques has yet to be conducted. In general the MDRD and Cockroft-Gault equations should result in similar dosage recommendations [26].

Another important drug elimination consideration in CKD patients is the accumulation of renally eliminated drug metabolites (table 1). Many drugs have metabolites that have pharmacologic activity. Some of these metabolites are also active drugs with similar activity in their own right (morphine, codeine). Some retained metabolites in CKD have therapeutic activity that differs from the parent compound (procainamide/n-acetylpro-cainamide). More common are the toxic metabolites that accumulate in CKD that contraindicate the use of the parent compound at all (meperidine, propoxy-phene).

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