Measurement of Glomerular Filtration Rate

Glomerular filtration rate (GFR) can be estimated from the plasma concentration of endogenous substances such as creatinine, and it is simple and cost-effective to do so, but the error on these estimates on an individual patient basis is high. Thus, GFR measurement is indicated in any clinical situation in which greater accuracy is required especially if the result will impact treatment decisions. Outside of the United States the radiopharmaceutical that has been most commonly used for measurement of GFR is Cr-51-EDTA. However, due to a recent reduction in supply, there has been a shift to Tc-99m-DTPA. The differences in clearance between these two tracers are small, and their clearance is comparable to the non-radiopharmaceutical markers inulin, iohexol and iothalamate. A few PET GFR tracers are currently under investigation for clinical use. Measurement of the urinary clearance of a tracer is the historical gold standard technique, however this method is prone to error due to difficulties with urine collection and inaccuracies associated with measuring residual activity in the bladder and renal drainage systems. Plasma clearance techniques provide a more practical and robust alternative and have good precision despite overestimating GFR slightly. Measurement of the area under the full plasma clearance curve is the reference method but due to the large number of blood samples required, it is largely limited to research settings. The slope-intercept and single-sample methods are simpler yet accurate alternatives that can be used in most patients. However, in patients with expanded third spaces or very low GFR (<25 mL/min/1.73 m(2)), different calculation methods are used that require blood sampling up to 24 hours. Camera-based methods are currently not recommended due to their imprecision. For the purposes of interpreting a GFR result, reliable reference data is available for adults and children, mostly derived from Cr-51-EDTA clearance measurements, but applicable to Tc-99m-DTPA GFR. GFR has notable biological variation and is susceptible to measurement errors, the combination of which translates into a high coefficient of variation for repeat measurements. Consequently, when serial measurements are performed, large changes (>20%) are required before a change can be regarded as significant. While biological variation is largely fixed, measurement errors can be minimized through careful work in combination with a system of thorough quality control checks. (C) 2021 Elsevier Inc. All rights reserved.