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).

Rationale & Objective: In prior research and in practice, the difference between estimated glomerular filtration rate (eGFR) calculated from cystatin C level and eGFR calculated from creatinine level has not been assessed for clinical significance and relevance. We evaluated whether these differences contain important information about frailty.
Study Design: A cohort analysis of the Systolic Blood Pressure Intervention Trial (SPRINT).
Setting & Participants: 9,092 hypertensive SPRINT participants who had baseline measurements of serum creatinine, cystatin C, and frailty.
Exposure: eGFRs calculated using CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations (eGFR cys and eGFR cr ), and eGFR Diff , calculated as eGFR cys -eGFR cr .
Outcomes: A validated 35-item frailty index that included questionnaire data for general and physical health, limitations of activities, pain, depression, sleep, energy level, self-care, and smoking status, as well as medical history, cognitive assessment, and laboratory data. We defined frailty as frailty index 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 eGFR Diff with frailty among all SPRINT participants. Adjusted proportional hazards regression was used to evaluate the association of eGFR Diff with adverse outcomes and mortality.
Results: Mean age was 68±9 (SD) years, mean eGFR cys and eGFR cr were 73±23 and 72±20mL/min/1.73m 2 , and mean eGFR Diff was 0.5±15mL/min/1.73m 2 . In adjusted models, each 1-SD higher eGFR Diff 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<0.01.
Limitations: Gold-standard measure of kidney function and assessment of muscle mass were not available.
Conclusions: The difference between eGFR cys and eGFR cr is associated with frailty and health status. Positive eGFR Diff is strongly associated with lower risks for longitudinal adverse outcomes and mortality, even after adjusting for chronic kidney disease stage and baseline frailty.
(Copyright © 2020 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Comment in: Am J Kidney Dis. 2020 Dec;76(6):752-753. (PMID: 33039174)