Quantitative Assessment of the Effect of Chronic Kidney Disease on the Nonrenal Clearance of 10 Drugs after Intravenous Administration

The investigation identified 10 publications that reported the individual values of total clearance (CL), renal clearance (CLr), nonrenal clearance (CLnr), and the glomerular filtration rate (GFR), in subjects with varying renal functions. We used these data to estimate extent and prevalence of changes in CLnr in chronic kidney disease (CKD) by examining the relationship between clearances and renal function. The investigation was restricted to drugs given intravenously and eliminated by mixed renal and nonrenal pathways. Six drugs showed a significant reduction of CLnr of 61% to 63% in subjects with severe renal impairment, suggesting that the decline of CLnr in advanced CKD can be clinically relevant and may not be uncommon. The decline of CLnr in CKD for these 6 drugs is linearly correlated with the decline of CLr. With 4 of the drugs studied, a significant reduction of CLnr in CKD was not seen. Renal clearance is a more reliable measure of renal function than GFR assessed by creatinine clearance. Chronic kidney disease affects the elimination more than the distribution of the 10 drugs.