Estimating renal function to reduce the risk of adverse drug reactions

Abstract

The aging process is characterized by relevant changes in pharmacokinetics. Renal function is known to decline with aging. However, as a result of reduced muscle mass, older individuals frequently have a depressed glomerular filtration rate (GFR) despite normal serum creatinine, and such a concealed renal insufficiency may impact significantly on the clearance of hydrosoluble drugs, as well as the risk of adverse drug reactions (ADRs) from hydrosoluble drugs. The assessment of renal function should thus be a mandatory item in the global examination of patient characteristics. Equations for estimating GFR have become very popular in recent years. However, different equations may yield significantly different estimated glomerular filtration rate (eGFR) values, which have important implications in dosing drugs cleared by the kidney. Current knowledge suggests that eGFR based on the Chronic Kidney Disease-Epidemiological Collaboration (CKD-EPI) study equation outperformed eGFR based on the Modification of Diet in Renal Disease (MDRD) study equation and creatinine clearance estimate based on the Cockcroft-Gault formula as a predictor of ADRs from kidney cleared drugs. More recently, the combined creatinine-cystatin C equation was shown to perform better than equations based on either of these markers alone in diagnosing CKD, even in older patients. However, its accuracy in predicting ADRs and usefulness in drug dosing is still to be investigated.