Measured Glomerular Filtration Rate: The Query for a Workable Golden Standard Technique

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.

Reliability of glomerular filtration rate estimating formulas compared to iohexol plasma clearance in critically ill children

“…Routine implementation of iohexol clearance measurement has previously been suggested in critically ill adults as a potential alternative for accurate GFR; however, this warrants further research in critically ill children [27,54,55]. Although CL iohexol is widely used as a standard method for GFR measurement in both non-critically ill adults and children, it should be noted that iohexol is used off-label for this purpose since in Europe it is only registered as a contrast agent, not as a GFR marker substance [14].…”

“…Despite we were able to lower the number of iohexol blood samples in our study without significant impact on the mGFR. Efforts should be made to standardize the iohexol clearance procedure to optimize its clinical merits and to allow future comparison of study results [14]. Last, we assumed a normal GFR for age as baseline in all patients and used an mGFR to classify patients according to the AKI and ARC criteria.…”

“…Moreover, inulin analytical assays are complex and expensive. Additionally, a major practical limitation lies in the fact that in most European countries, inulin is no longer available [14][15][16][17]. This forced clinicians to replace inulin clearance by other methods for GFR measurement.…”

Race-free estimated glomerular filtration rate equation in kidney transplant recipients: development and validation study

“…The choice of GFR measurement method was determined by the transplant centre’s preference, as markers differ in terms of availability, cost, and expertise. 30 Studies have shown that these methods perform similarly for measuring GFR 31 32 33 and that bias is low. 30 Supplementary table 5 summarises the laboratory methods used.…”

Bone broth ingestion and acute kidney injury following kidney transplant: a role for cystatin C

“…A nuclear medicine renal GFR Chromium-51 scan was performed on day 15 and the measured GFR result corrected for body surface area was 79 mL/min/1.73 m 2 . A serum sample the next day found the eGFR to be between 64 and 70 mL/min/1.73 m 2 , and may be accounted for alteration in volume status or alternatively procedural issues with the timing of Chromium-51 sampling 3…”