Evaluation of concordance and association with clinical outcomes across eGFR values calculated with eight different formulas in a large cohort of european patients with atrial fibrillation

Abstract Background In randomized clinical trials of Direct Oral Anticoagulants (DOACs), the assessment of renal function impairment glomerular filtration rate (eGFR) in patients with Atrial Fibrillation (AF) has predominantly utilized the Cockroft-Gault (CG) formula for estimating Creatinine clearance (CrCl). However, in clinical practice, several other formulas for estimating glomerular filtration rate (eGFR) are employed. Limited data exist regarding the evaluation and comparison of eGFR/CrCl in AF patients. Objectives This study aimed to assess the concordance in the categorisation of renal function in in 6 classes taking into account eight different formulas for eGFR/CrCl (CG, CKD-EPI, CG/body surface area [BSA], BIS1, LMK, EKFC, FAS, MDRD) and their associations with a composite outcome (Major Adverse Cardiovascular Events [MACE] and all-cause death) in AF patients. Methods A contemporary European AF patient registry was utilized, and eGFR/CrCl were calculated using CG, CKD-EPI, CG/BSA, BIS1, LMK, EKFC, FAS, and MDRD formulas. eGFR was categorized according to KDIGO classes, with CKD patients defined as having eGFR/CrCl <60 ml/min/m2. Concordance was estimated using weighted Cohen’s kappa. Associations were evaluated through adjusted Cox regression analyses for the composite outcome, and results were plotted as spline curves. Results: A total of 8516 patients were included in the analysis (Median [IQR] age: 70 [63-77] years; 3518 women, 41.3%). Among the formulas, EKFC exhibited the highest median values of eGFR and the lowest prevalence of CKD patients, while BIS1 had the lowest median eGFR values, and the FAS formula led to the highest prevalence of CKD patients [Figure 1]. In the concordance analysis, CKD-EPI demonstrated the highest concordance with all other formulas, even if Cohen’s kappa for measuring the degree of concordance ranged from 0.61 to 0.88 [Figure 1]. In adjusted Cox regression analyses, all formulas were associated with an increased risk for the composite outcome, progressively as eGFR decreased. When plotted as spline curves, the associations with the composite outcome visually showed a similar behaviour of risks across eGFR values in all formulas compared to the CG spline [Figure 2]. Conclusions Among AF patients, the CKD-EPI formula exhibited variable, but substantially good concordance with CG, CG/BSA, BIS1, LMK, EKFC, FAS, and MDRD formulas. All calculated eGFR values showed a strong association with the composite outcomes, similarly to the CG formula, with higher risk when renal function decreased.FIGURE 1FIGURE 2