The kidney: SUMMARY

Renal clearance of drugs is a dynamic process involving filtration, secretion and reabsorption. While seemingly as chaotic as a schoolyard at recess time, these transport mechanisms work in unison to clear potentially toxic drug metabolites. The clinical importance of renal tubular transport systems is not only limited to drug interactions and toxicity. Emerging evidence suggests that the expression of transport proteins or their activity can be altered in chronic renal failure. For example, animal models of chronic renal failure show overexpression of MRP2.

With the advent of new molecular biology techniques, an even greater knowledge of the molecular handling of drugs within the renal tubular cells is possible. An understanding of these secretory mechanisms and the properties of drugs handled by a variety of transport mechanisms may be useful in predicting drug pharmacokinetics and drug interactions. The discovery of P-gp within the renal tubular cell luminal membrane is particularly important because it offers an explanation for a variety of well-known drug interactions, such as that between digoxin and quinidine, whose mechanisms, until now, had not been understood. Once other tranport mechanisms are identified and their properties elucidated, specific pharmacologic agents may be selected to predictably alter pharmacokinetics in the hopes of either increasing drug efficacy, minimizing toxicity and drug interactions or effectively prescribing for patients with renal impairment.

This entry was posted in Kidney and tagged Drug transport; Kidney; P-glycoprotein; Rena drug handling; Transport protein.