Association of Low Glomerular Filtration Rate With Adverse Outcomes at Older Age in a Large Population With Routinely Measured Cystatin C

Background: The commonly accepted threshold of glomerular filtration rate (GFR) to define chronic kidney disease (CKD) is less than 60 mL/min/1.73 m(2). This threshold is based partly on associations between estimated GFR (eGFR) and the frequency of adverse outcomes. The association is weaker in older adults, which has created disagreement about the appropriateness of the threshold for these persons. In addition, the studies measuring these associations included relatively few outcomes and estimated GFR on the basis of creatinine level (eGFR(cr)), which may be less accurate in older adults. Objective: To evaluate associations in older adults between eGFR(cr) versus eGFR based on creatinine and cystatin C levels (eGFR(cr-cys)) and 8 outcomes. Design: Population-based cohort study. Setting: Stockholm, Sweden, 2010 to 2019. Participants: 82 154 participants aged 65 years or older with outpatient creatinine and cystatin C testing. Measurements: Hazard ratios for all-cause mortality, cardiovascular mortality, and kidney failure with replacement therapy (KFRT); incidence rate ratios for recurrent hospitalizations, infection, myocardial infarction or stroke, heart failure, and acute kidney injury. Results: The associations between eGFR(cr-cys) and outcomes were monotonic, but most associations for eGFR(cr) were U-shaped. In addition, eGFR(cr-cys) was more strongly associated with outcomes than eGFR(cr). For example, the adjusted hazard ratios for 60 versus 80 mL/min/1.73 m(2) for all-cause mortality were 1.2 (95% CI, 1.1 to 1.3) for eGFR(cr-cys) and 1.0 (CI, 0.9 to 1.0) for eGFR(cr), and for KFRT they were 2.6 (CI, 1.2 to 5.8) and 1.4 (CI, 0.7 to 2.8), respectively. Similar findings were observed in subgroups, including those with a urinary albumin-creatinine ratio below 30 mg/g. Limitation: No GFR measurements. Conclusion: Compared with low eGFR(cr) in older patients, low eGFR(cr-cys) was more strongly associated with adverse outcomes and the associations were more uniform.