Abstract
Inulin clearance has, for a long time, been considered as the reference method to determine measured glomerular filtration rates (mGFRs). However, given the known limitations of the standard marker, serum creatinine, and of inulin itself, and the frequent need for accurate GFR estimations, several other non-radioactive (iohexol and iothalamate) and radioactive (51Cr-EDTA, 99mTc-DTPA, 125I iothalamate) exogenous mGFR filtration markers are nowadays considered the most accurate options to evaluate GFR. The availability of 51Cr-EDTA is limited, and all methods using radioactive tracers necessitate specific safety precautions. Serum- or plasma-based certified reference materials for iohexol and iothalamate and evidence-based protocols to accurately and robustly measure GFR (plasma vs. urinary clearance, single-sample vs. multiple-sample strategy, effect of sampling time delay) are lacking. This leads to substantial variation in reported mGFR results across studies and questions the scientific reliability of the alternative mGFR methods as the gold standard to evaluate kidney function. On top of the scientific discussion, regulatory issues are further narrowing the clinical use of mGFR methods. Therefore, this review is a call for standardization of mGFR in terms of three aspects: the marker, the analytical method to assess concentrations of that marker, and the procedure to determine GFR in practice. Moreover, there is also a need for an endogenous filtration marker or a panel of filtration markers from a single blood draw that would allow estimation of GFR as accurately as mGFR, and without the need for application of anthropometric, clinical, and demographic characteristics.
Highlights
Accurate determination of the glomerular filtration rate (GFR) is essential for the diagnosis of early kidney disease
As inulin production and availability from European Union (EU) chicory crops is below market demand, and as the approach to determine inulin clearance is very laborious, most clinicians have abandoned this method and have replaced it with several alternative measured glomerular filtration rates (mGFRs) protocols, measuring the plasma and/or urinary clearance of radioactive
No standardized protocol is currently available for determining mGFR based on plasma iohexol disappearance [95], and no study has appropriately compared the performance of single- and multiple-sample iohexol methods with urinary inulin clearance as the gold standard reference [34]
Summary
Accurate determination of the glomerular filtration rate (GFR) is essential for the diagnosis of early kidney disease. Plasma or urinary clearances of exogenous GFR markers are considered the most accurate way to evaluate kidney function (measured GFR, mGFR). This approach is typically desired in cases of substantially diverging anthropometric properties. Several exogenous markers have been evaluated for this purpose including inulin, 51 Cr-ethylenediamine tetraacetic acid (51 Cr-EDTA), 99m Tc-diethylenetriamine pentaacetic acid (99m Tc-DTPA), 125 I-iothalamate, and some non-isotopic “cold” markers (iothalamate and iohexol) [7,8] This opinion paper provides an overview of these exogenous mGFR markers, along with their limitations, in chronic stable individuals.
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