Association of low glomerular filtration rate with adverse outcomes at older age in a large population with routinely measured cystatin C

Abstract

Background: The commonly accepted threshold of glomerular filtration rate (GFR) to define chronic kid ney disease (CKD) is less than 60 mL/min/1.73 m2. 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 per sons. In addition, the studies measuring these associa tions included relatively few outcomes and estimated GFR on the basis of creatinine level (eGFRcr), which may be less accurate in older adults. Objective: To evaluate associations in older adults between eGFRcr versus eGFR based on creatinine and cystatin C levels (eGFRcr-cys) and 8 outcomes. Design: Population-based cohort study. Setting: Stockholm, Sweden, 2010 to 2019. Participants: 82154 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 re placement therapy (KFRT); incidence rate ratios for recurrent hospitalizations, infection, myocardial infarc tion or stroke, heart failure, and acute kidney injury. Results: The associations between eGFRcr-cys and outcomes were monotonic, but most associations for eGFRcr were U-shaped. In addition, eGFRcr-cys was more strongly associated with outcomes than eGFRcr. For example, the adjusted hazard ratios for 60 versus 80 mL/min/1.73 m2 for all-cause mortality were 1.2 (95% CI, 1.1 to 1.3) for eGFRcr-cys and 1.0 (CI, 0.9 to 1.0) for eGFRcr, and for KFRT they were 2.6 (CI, 1.2 to 5.8) and 1.4 (CI, 0.7 to 2.8), respec tively. 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 eGFRcr in older patients, low eGFRcr-cys was more strongly associ ated with adverse outcomes and the associations were more uniform. Primary Funding Source: Swedish Research Council, National Institutes of Health, and Dutch Kidney Foundation.