Slope of Kidney Function and Its Association with Longitudinal Mortality and Cardiovascular Disease among Individuals with CKD

Significance Statement Among individuals with CKD, decreases in eGFR, or increases that are steeper than the average loss, have been associated with increased risks of death and cardiovascular events. Sarcopenia and chronic illness might explain why apparent eGFR improvement relates to poor outcomes. The authors investigated the association between slopes of eGFR (defined with yearly eGFR) and the risks of death and cardiovascular events in a prospective cohort of adults with CKD. They found that declines in eGFR greater than the average eGFR loss were associated with increased risks of death and cardiovascular events, despite multiple adjustments. However, neither rises in eGFR nor losses smaller than the average eGFR loss were associated with increases in such risks. These findings suggest that, in CKD, improving eGFR might not be associated with concerning outcomes. Background Slopes of eGFR have been associated with increased risks of death and cardiovascular events in a U-shaped fashion. Poor outcomes in individuals with rising eGFR are potentially attributable to sarcopenia, hemodilution, and other indicators of clinical deterioration. Methods To investigate the association between eGFR slopes and risks of death or cardiovascular events, accounting for multiple confounders, we studied 2738 individuals with moderate to severe CKD participating in the multicenter Chronic Renal Insufficiency Cohort (CRIC) Study. We used linear, mixed-effects models to estimate slopes with up to four annual eGFR assessments, and Cox proportional hazards models to investigate the association between slopes and the risks of death and cardiovascular events. Results Slopes of eGFR had a bell-shaped distribution (mean [SD], −1.5 [−2] ml/min per 1.73 m 2 per year). Declines of eGFR that were steeper than the average decline associated with progressively increasing risks of death (hazard ratio [HR], 1.23; 95% confidence interval [95% CI], 1.09 to 1.39; for a slope 1 SD below the average) and cardiovascular events (HR, 1.19; 95% CI, 1.03 to 1.38). Rises of eGFR or declines lower than the average decline were not associated with the risk of death or cardiovascular events. Conclusions In a cohort of individuals with moderate to severe CKD, we observed steep declines of eGFR were associated with progressively increasing risks of death and cardiovascular events; however, we found no increased risks associated with eGFR improvement. These findings support the potential value of eGFR slopes in clinical assessment of adults with CKD.