Abstract
BACKGROUND: Exposure to vitamin K antagonists (VKA) has been suggested to accelerate progression of chronic kidney disease (CKD) but robust clinical data are currently lacking. METHODS: We retrospectively evaluated the impact of VKA exposure on kidney function in patients with atrial fibrillation (AF) and CKD stage 3/4. Patients were prospectively followed within a primary care electronic database (median follow-up of 1.45 years). The kidney function trajectory over time, defined as the annualized change in estimated glomerular filtration rate (eGFR), was analyzed with linear mixed-effects regression including propensity score adjustment. RESULTS: 14 432 patients (median age 78 years, median CHA (2) DS (2)-VASc score 4 points) contributed 97 792 eGFR measurements (mean 6.8 measurements/patient; range: 1-197). Mean baseline eGFR was 50.3 mL/min/1.73 m(2); and declined by 1.10 mL/min/1.73 m(2)/year (95% CI: 0.91-1.28, P < 0.0001). In 7409 patients with VKA exposure, CKD progression was significantly faster compared to patients without VKA exposure (5-year absolute eGFR loss from baseline: 6.0 mL/min/1.73 m(2) vs 4.5 mL/min/1.73 m(2), for an absolute 5-year excess eGFR decline with VKA exposure of 1.5 mL/min/1.73 m(2) (95% CI: 0.4-2.7, P = 0.002). These results prevailed upon adjusting for CHA (2) DS (2)-VASc score and other potential imbalances in prognostic variables, and in several sensitivity analyses. In the group without documented VKA exposure, 1775 VKA patients (24%) and 1012 patients (14%) developed a 30% decline in eGFR during follow-up (P < 0.0001). CONCLUSIONS: In patients with AF and CKD, VKA use is associated with accelerated eGFR decline. Within the limitations of a retrospective analysis, this finding supports the "VKA-renal-calcification hypothesis." However, although statistically significant, the excess loss in eGFR over 5 years with VKA was modest.