Clearance by glomerular filtration

Clearance by glomerular filtration (Cl_GF) is the contribution to renal clearance by filtration into Bowman’s capsule. In a young, healthy adult male kidney, glomerular filtration occurs at around 120 ml/minute (or 7.2 l/hour, equal to around 10% of blood flow through the kidneys, and corresponding to the glomerular filtration rate, or GFR). While young healthy females show GFR values lower than do male subjects, rates are only marginally lower when corrected for body size. This correction is made through expressing GFR with respect to body surface area; as such, young healthy adults have a GFR of around 100 ml/min/1.73 m². The GFR falls with age, at a rate of around 4 ml/min/1.73 m² every decade until around 50 years of age, and then more rapidly thereafter.

Along with about 10% of the plasma volume, small solutes such as salts, metabolic waste products and drugs / drug metabolites are also filtered. Initially, they are present in the filtrate at concentrations similar to those in the plasma. The value for Cl_GF is thus identical to an individual’s GFR. The concentration of solutes in the filtrate increases as filtrate passes through a kidney nephron, as a result of clearance by secretion and of reabsorption of water, and may decrease in the latter stages of their journey through a nephron as a result of reabsorption back into the bloodstream.

Since GFR plays a significant role in contributing to renal clearance of drugs, then Cl_GF will be highest, at around 100 ml/min/1.73 m², in young, healthy adults, when no drug in the blood is bound to plasma protein. Cl_GF will fall with age, averaging around 70 ml/min/1.73 m² in healthy 80-years-old subjects, with some individuals in that group showing values as low as 50. GFR, and thus Cl_GF, also fall markedly in several disease states, and particularly in chronic kidney disease (CKD). For drugs that are cleared predominantly by the kidneys, that have a narrow therapeutic window and that may cause serious side-effects as a consequence of exceeding the maximum tolerated concentration, it is routine practice to estimate the GFR in patients with renal insufficiency so that dosing adjustments can be made. This is generally accomplished by determining a patient’s urinary creatinine clearance rate.