Age-dependent changes of the kidneys: Pharmacological implications

About 40% of the intoxications after drug administration occur in the elder ly. A significant proportion of the disease states in elderly patients is r elated to adverse reactions to prescribed drugs. Declining renal function, a reduction in both renal blood flow and glomerular filtration rate, is a m ajor contributor to drug toxicity in the elderly. Therefore, a review (base d on newer papers from Medline) of age-dependent changes of the kidneys and their consequences for drug therapy in geriatric patients is presented. Re nal changes that occur with aging are: a decrease of renal weight, a thicke ning of the intrarenal vascular intima, sclerogenous changes of the glomeru li, and infiltration of chronic inflammatory cells and fibrosis in the stro ma. Altered renal tubular function, including impaired handling of water, s odium, acid, and glucose, is also frequently present in old age. Impaired ' endocrinologic' functioning manifested by changes of the renin-angiotensin system, vitamin D metabolism, and antidiuretic hormone responsiveness has b een reported. The aging kidney is constantly exposed to the effects of a va riety of potential toxic processes, i.e., drugs and chronic illnesses inclu ding hypertension, diabetes, and atherosclerotic disease. Renal changes tha t occur with aging also consist of impairment in the ability to concentrate urine and to conserve sodium and water. These physiological changes increa se the risks of volume depletion and prerenal type of acute renal failure. A frequent cause of acute renal failure in the elderly is drug-induced neph ropathy. Nonsteroidal anti-inflammatory drugs, antibiotics, and diuretics a re most often involved. Due to the age-dependent decline of renal function, the pharmacokinetics of many drugs are altered in elderly patients. Theref ore, the most important renal function to monitor with aging is the creatin ine clearance. Changes in pharmacokinetics of many drugs and most decisions on drug dosage can be based on this information alone, as tubular function s of the kidney decrease at rates paralleling the age-dependent decrease in glomerular filtration rate (which is approximately measured by the creatin ine clearance). As a conclusion, age-dependent changes of renal function ar e not only responsible for changes in pharmacokinetics and pharmacodynamics . In many cases, the kidneys are the target organ of adverse drug reactions too.