Renal disease can cause profound changes in the body that must be evaluated by assessing the patient’s condition and medical history. Renal dysfunction is often accompanied by reduced protein–drug binding and by reduced glomerular filtration rate in the kidney. Some changes in hepatic clearance may also occur. While there is no accurate method for predicting the resulting in vivo changes, a decrease in albumin may increase fu, or the fraction of free plasma drug concentration in the body. The fu is estimated from fu = 1 – fb, where fb is the fraction of bound plasma drug. For the uremic patient, the fraction of drug bound fb′ is affected by a change in plasma protein: fb′/fb = p′/4.4, where p is the normal plasma protein concentration
(4.4 g/dL assuming albumin is the protein involved) and p′ is the uremic plasma protein concentration; fb′ is the fraction of drug bound in the uremic patient. Since fu′ or the fraction of unbound drug is increased in the uremic patient, the free drug concentration may be increased and, sometimes, lead to more frequent side effects. On the other hand, an increase in plasma free drug in the uremic patient is offset somewhat by a corresponding increase in the volume of distribution as plasma protein–drug binding is reduced. Reduction in GFR is more definite; it is invariably accompanied by a reduction in drug clearance and by an increase in the elimination half-life of the drug.