A study of more than 82,000 older adults receiving outpatient measurements of estimated glomerular filtration rate (eGFR) found that measuring eGFR based on creatinine and cystatin C levels (eGFRcr-cys) was more strongly associated with adverse outcomes than measuring eGFR with only creatinine levels (eGFRcr). The study is published in Annals of Internal Medicine.

Current guidelines define a GFR below 60 ml/min/1.73 m² for 3 months as chronic kidney disease, even in the absence of albuminuria. eGFRcr is usually used in routine practice, rather than measured GFR to define and stage chronic kidney disease.

An eGFRcr below 60 mL/min/1.73 m² is usually associated with adverse outcomes including kidney failure and all-cause mortality. However, this threshold is more common in older adults than in younger adults and less strongly associated with adverse outcomes in this population. This has created disagreement about the appropriateness of the threshold for these persons.

Researchers studied data from a Swedish cohort at or above age 65 years with simultaneous measurements of creatinine and cystatin C to evaluate associations in older adults between eGFRcr versus eGFRcr-cys and 8 outcomes. The authors found that eGFRcr-cys below 60 mL/min/1.73 m² had stronger associations with clinical outcomes including all-cause mortality, cardiovascular mortality, hospitalization, infection, stroke, heart failure, kidney failure with replacement therapy, and acute kidney injury than eGFRcr, even in the absence of albuminuria.

The weaker associations with eGFRcr are likely explained because of limitations of creatinine as a filtration marker rather than the GFR threshold, since eGFRcr-cys is a more accurate reflection of measured GFR than eGFRcr. They note that these data indicate that CKD stage G3+ (GFR <60 mL/min/1.73 m²) at older age is associated with a wider range of outcomes than previously recognized.

These data support the current GFR threshold of below 60 ml/min/1.73 m² for defining chronic kidney disease. While several clinical guidelines for evaluating and managing chronic kidney disease recommend measuring cystatin C, this practice is limited in most countries. The authors suggest that the broad range of risks associated with chronic kidney disease at older age is better appreciated when cystatin C is included in GFR estimation.

The authors of an accompanying editorial from the Cleveland Clinic Health System say the study demonstrates that creatinine and cystatin C have limitations as biomarkers and may lead to errors in estimation of measured GFR. Both biomarkers have non-GFR determinants that may detect pathophysiology unrelated to kidney function but associated with poor health outcomes. This may explain why eGFRcr and eGFRcr-cys have different associations with clinical outcomes.