Creatinine: From physiology to clinical application

•Estimating kidney function is challenging and critically ill patients.•Creatinine is a widely used functional biomarker and has substantial shortcomings.•Use of novel functional biomarkers with creatinine provides additional information.•Creatinine could be used for the estimation of muscle mass or clinical outcomes.•New technologies for direct GFR measurement could overcome creatinine limitations. Estimating static kidney function accurately and detecting changes in kidney function in a timely fashion are challenging but critically important tasks. Serum creatinine is the most widely used functional biomarker of the kidney. However, its use is associated with substantial shortcomings. Understanding these shortcomings is critical in allowing accurate interpretation of creatinine values and translating them into changes in kidney function. In this review, the pathways involved in creatinine generation and metabolism as well as the techniques involved in measuring creatinine concentrations are discussed. This allows for the discussion of the value and pitfalls in using creatinine as a marker of kidney function. In addition, information regarding alternative functional biomarkers of the kidney is provided.