AGING MEDIATED CHANGES IN RENAL EXCRETION OF ORGANIC ANIONS

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The broad long term objective of this research is to characterize the effects of aging on renal drug excretion. Although it is well established that becoming older is accompanied by anatomic and physiologic changes in renal function, there is a paucity of data regarding the differential effects of aging on the individual mechanisms of renal excretion of medications: filtration, secretion and reabsorption. The first specific aim of the research is to establish the isolated perfiised rat kidney (IPK) model as a useful tool for studying the effects of aging on physiologic renal function and renal clearance. Establishing the IPK as a model of renal drug disposition in geriatric subjects would allow correlation between aging and the numerous factors which affect renal drug excretion. A second aim of the research is to test the validity of the "Whole Nephron Hypothesis" which assumes that reductions in glomerular filtration secondary to aging or disease are accompanied by parallel reductions in secretion and reabsorption. Whereas this hypothesis is the basis for making dosage adjustments based on glomerular filtration rate (GFR), reports in the literature suggest that tubular secretion of certain medications can be maintained in the presence of decreased OFR. Studying the effects of aging on the renal excretion para-aminohippurate and acetazolamide, compounds of contrasting degrees of renal extraction, will permit assessment of the linearity between filtration and secretory mechanisms of the kidney. These findings could challenge present guidelines for GFR-based dosing of medications in geriatric patients and possibly reduce the incidence of drug-related morbidity in this patient population.