Principles of drug administration in renal insufficiency

Normal renal function is important for the excretion and metabolism of many drugs. Renal diseases which affect glomerular blood flow and filtration, tubular secretion, reabsorption and renal parenchymal mass alter drug clearances and lead to the need for alterations in dosage regimens to optimise therapeutic outcome and minimise the risk of toxicity. Renal disease is increasing and the cost of care has risen progressively over the past decade. Part of these costs is related to inappropriate drug therapy and excessive drug use. Although there are a variety of methods for evaluating the various aspects of renal function, the most practical and commonly used clinical measure of renal function is estimated creatinine clearance (CLCR) as a marker for glomerular filtration. This is useful since alterations in drug clearance are proportional to alterations in CLCR, and this relationship is used as the basis for changing doses and dosage intervals for drugs which are largely renally excreted. Two populations, neonates and the elderly, are at risk of inappropriate drug dosage due to physiological changes in renal function. Estimated CLCR may not be the best method of evaluating renal function in these patients, and dosage regimens should be carefully considered. Renal insufficiency and concurrent drug therapy used in these populations can either increase or decrease drug absorption, depending on the particular agent. Drug distribution may be altered in renal insufficiency due to pH-dependent protein binding and reduced protein (primarily albumin) levels. Interestingly, renal disease may affect hepatic as well as renal drug metabolism; the exact mechanisms for these changes are not well understood. The most important quantitative pharmacokinetic change is excretion. Glomerular filtration and tubular process may both be affected but not to the same extent, and the type of renal disease may differentially affect filtration and excretion. Drug removal by dialysis is dependent on a number of factors, including the characteristics of a particular drug and the type of dialysis and equipment used. Therapeutic outcomes may be evaluated using end-points such as plasma concentrations, patient outcomes such as reduction in fever or negative cultures, and system-wide changes such as drug-use or laboratory-use patterns.