Renal clearance

The volume of plasma (i.e. the volume of the total volume of distribution for a drug) that is cleared of drug in unit time as a consequence of drug being removed from blood passing through the kidneys. Renal clearance results from filtration of drug at Bowman’s capsule (around 7.2 litres/hour in a pair of healthy kidneys), plus clearance by secretion from the blood that is NOT filtered at Bowman’s capsule (so this could be as much as 65 litres/hour if drug is unbound and with transporters removing all drug from the blood). However some or all of this filtered/secreted drug may be reabsorbed from the filtrate if the drug is present in filtrate in a lipid-soluble (uncharged) form. If all of the drug is reabsorbed then renal clearance is zero.

The magnitude of reduction in the glomerular filtration rate (GFR) as a result of chronic kidney disease (CKD) or other condition affecting renal filtration gives a quantitative indication of the degree of reduction in renal clearance for a drug. This may necessitate a change to a chronic dosing regimen in order to achieve a similar target steady state concentration to that which would be achieved with a standard dosing regimen in an individual with normal renal function. For example, for a drug that is cleared entirely by the kidneys, a 50% reduction in GFR would be countered by a 50% reduction in the dosing rate. However, if a drug is only partially cleared by the kidneys, then only that portion of the total body clearance for which the kidney is responsible should be adjusted. For example, in a patient with 50% reduction in GFR, a drug which is cleared 40% by the liver and 60% by the kidneys would require a reduction in the dosing rate to 70% of that in a person with full renal function. This value represents the sum of the 40% of clearance carried out by the liver, plus half of the 60% of clearance carried out by the kidneys.