Glomerular Filtration Markers: Current and Emerging Insights

Glomerular filtration markers are exogenous or endogenous solutes that are eliminated from the circulation primarily by glomerular filtration. Their rate of elimination is directly related to the GFR, and their plasma concentration is inversely related to the GFR. GFR cannot be measured directly in humans, but it can be assessed by using filtration markers-either as measured GFR (mGFR) from clearance measurements using exogenous filtration markers (such as iothalamate and iohexol) or as eGFR from estimating equations using plasma concentrations of endogenous filtration markers (metabolites, such as creatinine, and low molecular weight proteins, such as cystatin C). Thus, both mGFR and eGFR may differ from true GFR, and understanding the physiologic processes affecting filtration markers is required for clinical evaluation of GFR. Processes other than GFR that affect the plasma concentration of filtration markers are collectively defined as non-GFR determinants. By design, exogenous filtration markers are minimally affected by non-GFR determinants, but both urinary and plasma clearance measurements are associated with error in mGFR. By contrast, by definition, all endogenous filtration markers are affected by non-GFR determinants, but not by error in clearance measurements. The major limitations of mGFR procedures are complexity and inconvenience of clearance measurements, which constrain their utility in clinical practice. The major limitation of eGFR is error because of variation in the non-GFR determinants of the filtration markers, which can be minimized by use of a panel of markers (panel eGFR). There is ongoing interest in the discovery of new exogenous filtration markers that would enable widespread implementation of mGFR procedures and novel metabolite and low molecular weight endogenous filtration markers that would enable a panel eGFR. In this review, we discuss current and emerging insights into existing and novel filtration markers.