Impact of kidney function overestimation by creatinine compared to cystatin C in patients with atrial fibrillation

Background Differences between creatinine-based and cystatin C-based glomerular filtration rate estimations (eGFRdiff) have been associated with adverse outcomes. Aim To investigate the prevalence of eGFRdiff and its associations with clinical outcomes in patients with AF. Methods We analyzed 3,804 patients with AF enrolled in two prospective, multicenter cohort studies. The eGFRdiff was calculated for each patient as the 2021 CKD-EPI creatinine-cystatin C equation minus the creatinine-only equation. Patients were stratified into three groups: eGFRdiff >10, -10 to 10, and <-10 mL/min/1.73 m². Associations with high-sensitivity troponin T (hs-TnT) and NT-proBNP, major adverse cardiovascular events (stroke/systemic embolism, myocardial infarction and cardiovascular death) and first heart failure (HF) hospitalization were assessed. Results Mean age was 71 years, 28% were female, and 49% had paroxysmal AF. An eGFRdiff of >10, -10 to 10 and <-10 ml/min/1.73 m2 was present in 17.7%, 71.7%, and 10.6% of the patients, respectively. Over a median follow-up of 8 years, 985 composite endpoints for MACE and 831 HF events occurred. With decreasing eGFRdiff categories, the incidence rates per 100 patient-years increased for MACE (1.7, 3.9, 6.8) and for HF events (1.2, 3.5, 6.1) (Figure). Hs-TnT and NT-proBNP were inversely correlated with eGFRdiff. In multivariable-adjusted linear models, lower eGFRdiff was associated with a higher risk for MACE (HR 1.50, 95% CI 1.26–1.79; p<0.001) and HF-hospitalization (HR 1.49, 95% CI 1.23–1.81; p<0.001) compared with the reference group (eGFRdiff -10 to 10). Conclusion A clinically relevant eGFRdiff was common in a large proportion of patients with AF. Cardiac biomarker levels increased with a larger creatinine-based eGFR overestimation. Patients with eGFRdiff <-10 ml/min/1.73 m2 had a high risk of adverse outcomes.