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Chronic kidney disease is an increasing health burden. Estimating equations using serum concentrations of creatinine and cystatin C facilitate the assessment of kidney function as reflected in estimated glomerular filtration rate (eGFR). Reduced eGFR is associated with increased risk for numerous adverse outcomes and is an important aspect in many clinical situations. However, current equations are suboptimal in some clinical settings. The review focuses on approaches to improve the estimation of GFR and aims to familiarize the reader with the underlying methodological hypotheses how new markers could contribute to improve the overall performance of estimating equations.Low molecular weight proteins such as β-trace-protein and β-2-microglobulin, as well as newly discovered metabolites, show promise as new filtration markers, as they might be beneficial in populations in which creatinine or cystatin C are inaccurate. We propose that the combination of multiple novel markers, alone or in combination with creatinine, cystatin C or demographics, can potentially improve GFR estimation. For special populations such as dialysis patients, separate equations have been developed to estimate residual kidney function.Current GFR estimating equations are an essential part of routine clinical practice but have limitations. The use of multiple markers combined in a single equation appears to be the most promising approach. Future research is required to validate proposed equations in diverse populations.