New biomarkers for estimating glomerular filtration rate

Glomerular filtration rate (GFR) is still considered the best indicator for kidney function assessment. In clinical routine, creatinine-based GFR estimation is the most widely used method for the evaluation of kidney function in healthy and kidney-diseased individuals. In recent years, researchers and clinicians have become aware of the limitations when using solely serum creatinine for kidney function assessment as it can lead to inaccurate estimation of GFR, particularly in populations with abnormal muscle mass distribution or generation. Several novel biomarkers have been proposed to improve accuracy and precision of GFR estimation, of which cystatin C, a low molecular weight protein, has proven to contribute considerable benefit to kidney function assessment when combined with creatinine. Importantly, the use of cystatin C as filtration marker has gained even more clinical relevance since the introduction of international reference standards available for assay manufacturers led to a harmonization of cystatin C analysis by minimizing inter- and intra-laboratory variability. Beta-trace protein (BTP) and beta-2 microglobulin (B2M) are two renal biomarkers with established but non-standardized assays that have been proposed as promising novel candidates for improving GFR estimation. In summary, a variety of new filtration markers and methods are available to assist clinicians in the evaluation of kidney function. The ongoing investigations of novel markers and metabolomics will help to identify their utility and may clarify whether they have the potential to improve the care of patients with and without kidney disease. This review will discuss the physiology, measurement and clinical potential of cystatin C, BTP, and B2M, will give a brief overview of current achievements in the field of kidney metabolomics and a short introduction to the concept of “rescaling” renal biomarkers.