The Difference Between Cystatin C- and Creatinine-Based Estimated GFR and Associations With Frailty and Adverse Outcomes: A Cohort Analysis of the Systolic Blood Pressure Intervention Trial (SPRINT)

Abstract Rationale & Objective In prior research and in practice, the difference between eGFR calculated from cystatin C and from creatinine has not been assessed for clinical significance and relevance. We evaluated if these differences contain important information about frailty. Study Design A cohort analysis of the Systolic Blood Pressure Intervention Trial (SPRINT). Setting & participants: 9092 hypertensive SPRINT participants who had baseline measurements of serum creatinine, cystatin C, and frailty. Exposure eGFRs calculated using CKD-EPI equations (eGFRCys and eGFRCr), and eGFRDiff calculated as eGFRCys - eGFRCr. Outcomes A validated 35-item frailty index (FI) that included questionnaire data on general and physical health, limitations of activities, pain, depression, sleep, energy level, self-care, smoking status, as well as past medical history, cognitive assessment, and laboratory data. We defined frailty as a FI score > 0.21 (range: 0 - 1). The incidence of injurious falls, hospitalizations, cardiovascular events, and mortality was also recorded. Analytical approach We used logistic regression to model the cross-sectional association of baseline eGFRDiff with frailty among all SPRINT participants. Adjusted proportional hazards regression was used to evaluate the association of eGFRDiff with adverse outcomes and mortality. Results Mean age was 68 (±9) years; mean eGFRCys was 73 (±23), mean eGFRCr was 72 (±20), and mean eGFRDiff was 0.5 (±15) mL/min/1.73 m2. In adjusted models, each SD higher eGFRDiff was associated with 24% lower odds of prevalent frailty (OR=0.76; 95%CI: [0.71; 0.81]), as well as with lower incidence rate of injurious falls (HR=0.84; 95%CI: [0.77; 0.92]), hospitalization (HR=0.91; 95%CI: [0.88; 0.95]), cardiovascular events (HR=0.89; 95%CI: [0.81; 0.97]), and all-cause mortality (HR=0.71; 95%CI: [0.63; 0.82]), p Limitations Gold standard measure of kidney function and assessment of muscle mass were not available. Conclusions The difference between eGFRCys and eGFRCr is associated with frailty and health status. Positive eGFRDiff is strongly associated with lower risks of longitudinal adverse outcomes and mortality, even after adjusting for CKD stage and baseline frailty.