Renal Handling of Drugs

Important mechanisms involved in the renal excretion and reabsorption of drugs have been reviewed by Reidenberg (15) and are shown in Table 5.1. 

The kidney plays a major role in the clearance of insulin from the systemic circulation, removing approximately 50% of endogenous insulin and a greater proportion of insulin administered to diabetic patients (19). Insulin is filtered at the glomerulus and reabsorbed by proximal tubule cells, where it is degraded by proteolytic enzymes. Insulin requirements are markedly reduced in diabetic patients with impaired renal function. Imipenem and perhaps other 

Despite the paucity of detailed studies, it is possible to draw some general mechanistic conclusions from renal clearance values  

Effects of Impaired Renal Function on Nonrenal Metabolism 

Most drugs are not excreted unchanged by the kidneys but first are biotransformed to metabolites that then are excreted. Renal failure not only may retard the excretion of these metabolites, which in some cases have important pharmacologic activity, but, in some cases, alters the nonrenal as well as the renal metabolic clearance of drugs (15, 24). The impact of impaired renal function on drug metabolism is dependent on the metabolic pathway, as indicated in Table 5.2. In most 

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Lin JH, Lin T. Renal handling of drugs in renal failure. I. Differential effects of uranyl nitrate- and glycerol-induced acute renal failure on renal excretion of TEAB and PAH in rats. J Pharmacol Exp Ther 1988 246 896-901. 

Kamiya A, Okumura K, Hori R. Quantitative investigation of renal handling of drugs in dogs with renal insufficiency. Pharm Sci 1984 74 892-896. 

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