Renal Impairment and Drug Clearance

Renal disease causes impairment in the clearance of many drugs by the kidney. Correlations have been established between creatinine clearance and clearance of digoxin, lithium, procainamide, aminoglycoside, and many other drugs. The clearance of a drug is closely related to glomerular filtration rate (GFR), and creatinine clearance is a valid way to determine GFR. Serum cystatin C is another marker of GFR. In clinical practice, the degree of renal impairment is widely assessed by using the serum creatinine concentration and creatinine clearance predicted using Cockcroft-Gault formula (77). However, creatinine clearance may be a poor predictor of GFR under certain pathological conditions. Caution should be exercised when medications are prescribed to elderly patients because they may have unrecognized renal impairment. Serum creatinine remains normal until GFR has fallen by at least 50%. Nearly half of the older patients have normal serum creatinine but reduced creatinine clearance. Dose adjustments based on renal function is recommended for many medications in elderly patients even with medications that exhibit large therapeutic windows (78). Dosage adjustments are made for amikacin, gentamicin, tobramycin, and vancomycin based on GFR. Schuck et al. (79), based on a study with 126 patients, concluded that no significant differences exist between serum concentrations of creatinine or its predicted creatinine clearance by Cockcroft-Gault formula, cystatin C, and predicted GFR with regard to dose adjustments. O'Riordan et al. (80), using 22 healthy volunteers who received a single dose of intravenous digoxin, concluded that serum cystatin C is no better than serum creatinine concentration in predicting renal clearance of digoxin. In contrast, Hoppe et al. (81) reported that serum cystatin C is a better predictor of drug clearance than serum creatinine concentrations.

Renal disease also causes impairment of drug protein binding because uremic toxins compete with drugs for binding to albumin. Such interaction leads to increases in concentration of pharmacologically active free drug concentration, which is clinically more important for strongly protein-bound drugs. This topic is addressed in Chapter 2.

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