Associations of estimated glomerular filtration rate and albuminuria with adverse outcomes: An individual participant meta-analysis

Importance: Chronic kidney disease (low eGFR or albuminuria) affects approximately 14% of people in the United States. Objective: To evaluate associations of lower eGFR using creatinine alone (eGRFcr), lower eGFR using creatinine combined with cystatin C (eGFRcr-cys), and higher albuminuria with adverse kidney outcomes, cardiovascular outcomes, and other health outcomes. Design, setting, participants: Retrospective individual-level data analysis of 27,503,140 participants from 114 global cohorts (eGFRcr) and 720,736 participants from 20 cohorts (eGFRcr-cys) and 9,067,753 participants from 114 cohorts (albuminuria) from 1980 to 2021. Exposures: CKD-EPI 2021 equations for eGFRcr and eGFRcr-cys; albuminuria estimated as urine albumin-to-creatinine ratio (ACR). Main outcomes and measures: The risk of kidney failure with replacement therapy, all-cause mortality, cardiovascular mortality, acute kidney injury, any hospitalization, coronary heart disease, stroke, heart failure, atrial fibrillation, and peripheral artery disease. Analyses were performed within each cohort and summarized with random-effect meta-analyses. Results: Within the eGFRcr population (mean age: 54 years, 51% women), mean eGFRcr was 90 ml/min/1.73 m2 (SD, 22) and median ACR was 11 mg/g (interquartile range 8-16 mg/g). Within the eGFRcr-cys population (mean age: 59 years, 53% women), mean eGFRcr-cys was 88 ml/min/1.73 m2 (SD, 22) and median ACR was 9 mg/g (interquartile range 6-18 mg/g). Lower eGFR (whether based on eGFRcr or eGFRcr-cys) and higher ACR were each associated with higher risk of all ten adverse outcomes, including in the mildest categories of CKD. For example, among people with ACR <10 mg/g, an eGFRcr 45-59 ml/min/1.73 m2 was associated with significantly higher hospitalization rates, compared to eGFR 90-105 ml/min/1.73 m2 (adjusted hazard ratio 1.28, 95% CI: 1.24-1.32; 101 vs. 79 events per 1000 person-years; excess absolute risk 22 events per 1000 person-years, 95% CI: 19 to 25). Conclusions and relevance: In this retrospective analysis of 114 cohorts, lower eGFRcr, lower eGFRcr-cys, and higher ACR were each associated with increased rates of 10 adverse outcomes, including adverse kidney outcomes, cardiovascular diseases, and hospitalization.