Acute and chronic nephropathy induced by fluindione must be addressed

Abstract

BACKGROUND: Among the vitamin K antagonists (VKA), indanedione-derived VKA is suspected to induce an immunoallergic risk. One indanedione-derived VKA, fluindione, is still being used in France. The aim of this study was to evaluate the contribution of VKA to acute and chronic nephritis. METHODS: Twenty-four cases of biopsy proven acute interstitial nephritis (AIN) were retrospectively selected, based on a first intake of VKA within the previous 12 months as well as an increase of at least 50% of the basal level of serum creatinine. The 24 cases were all treated with fluindione VKA and not with coumarinic VKA. RESULTS: The subjects studied included 20 men and 4 women, with a mean age of 73.0±9.3 years (range: 44-84). The delay between fluindione introduction and the appearance of an AIN, proven by biopsy when available, was 11.9±6.9 weeks (range: 3-28). Creatinine increased from 123.0±56.4 μmol/L (range: 56-335) at fluindione introduction to 460.7±265.3 μmol/L (range: 109-1200) at the time of AIN discovery. The treatment then consisted of stopping the fluindione and introducing steroids for 21 patients. If a VKA was necessary, fluindione was replaced by a coumarinic VKA. After 6 months, 1 patient died and 15 patients presented severe chronic kidney disease (CKD Stages 4-5). Two patients still required chronic dialysis after 6 months and five patients after 3 years. Patients with pre-existing kidney disease were more prone to develop severe CKD with fluindione. CONCLUSION: In this large study, arguments are presented to incriminate fluindione in the induction of acute and chronic nephritis.