Implications of the cystatin C/creatinine discordance

Clinicians may estimate the glomerular filtration rate using serum creatinine (eGFRcr) or cystatin C (eGFRcys). But the difference between these estimates (eGFRdiff) is often large. In addition to presenting a clinical conundrum, eGFRdiff is associated with adverse outcomes. Often, these associations have been attributed to low muscle mass, wherein creatinine production is low, artificially increasing eGFRcr above eGFRcys. Less prominent theories propose the adverse associations may be due to artificial depression of eGFRcys when cystatin C production is increased by obesity or inflammation or when cystatin C clearance is decreased relative to creatinine clearance (shrunken pore syndrome).

Recent analyses have revealed our understanding of the determinants and consequences of eGFRdiff remains poor. Models incorporating iothalamate GFR measurements and objective measures of muscle mass, obesity, inflammation, shrunken pore syndrome, have explained only a minority of the variation in eGFRdiff among individuals. Moreover, adjustment for these factors does not extinguish the associations with outcomes.

The pathophysiology underlying the associations between eGFRdiff and adverse outcomes remains poorly understood. Until our understanding improves to allow prediction of whether eGFRcr or eGFRcys is likely to be more accurate in a particular patient, the combined equation estimate should be favored.