The difference between glomerular filtration rate (GFR) estimated by cystatin C and creatinine (eGFRdiff, defined as eGFRcys−eGFRcr) has been repeatedly associated with adverse outcomes, often ascribed to low muscle mass. However, it is unclear to what extent putative determinants of eGFRdiff, such as low muscle mass, explain associations between eGFRdiff and the outcomes of death and heart failure. Determinants of eGFRdiff have not been investigated to assess their impacts on eGFRcys, eGFRcr, and ultimately eGFRdiff in a dataset with measured GFR.