GFR cannot be measured directly but is estimated by measuring the urine-clearance of an ideal marker for filtration. The clearance of a substance is, by definition, the amount of that substance that is filtered from the plasma per time unit. Clearance for a substance, x, is:
Cx = (Ux ⋅ V)/Px
where Cx is the clearance for x, Ux is the urine concentration of x, V is the urine production per time unit, and Px is the plasma concentration of x. An ideal filtration marker is a substance that is filtered without limitations in the glomerulus, and is neither excreted or reabsorbed in the tubules nor meatbolised or changed during the excretion of urine. When these elements are filled, the Cx = GFR.
Inulin is the gold standard when measuring GFR, but the procedure requires continuous intravenous infusion of the substance, multiple blood tests, and bladder catheterization. Simpler procedures with a bolus injection of a substance (for example iohexol) can also be used, but with more sources of error.
GFR can be estimated (eGFR) by measuring creatinine clearance or by using plasma creatinine in formulas for eGFR. Creatinine is produced in the muscle and absorbed from the diet (meat). Creatinine is released relatively constantly from muscle cells, filtered in the glomeruli, and is not reabsorbed in the tubules but about 10-40 % of creatinine that is excreted in the urine is from tubular secretion. This means that plasma creatinine under stabile conditions generally varies inversely with GFR. A halving in the excretion of creatinine in the urine will lead to retention of creatinine in the plasma until the concentration is doubled and a new equilibrium is established between the plasma concentration and the excretion in urine. In reality, the increase in plasma creatinine is smaller as there is also tubular secretion of creatinine.
There are multiple formulas to account for tubular secretion and relations between muscle mass, gender and age: Cockroft-Gault, MDRD, and CKD-EPI are most commonly used.
Cystatin C is a low-molecular protein that is a member of the large family of cysteine protease inhibitors. It is filtered in the glomeruli and not reabsorbed but is metabolised in the tubules. Cystatin C cannot be used directly to measure clearance. However, cystatin C is likely better than creatinine for calculating GFR in patients with slightly decreased kidney function and where decreased creatinine production is expected, such as the elderly, children, kidney transplanted, and in cirrhosis.