title: Safety, efficacy and renal effect of febuxostat in patients with moderate-to-severe kidney dysfunction.
abstract: Hyperuricemia (HU) is common in patients with chronic kidney disease (CKD), and accumulating evidence suggests it has a pathogenic role in the progression of the disease. However, a major challenge in treating patients with HU is the adverse effects caused by urate-lowering drugs used to treat CKD. Because of these untoward effects, doses need to be reduced, which leads to suboptimal efficacy. Febuxostat has been shown to be highly efficacious in reducing serum uric acid (sUA) and is well tolerated in patients with mild kidney dysfunction. However, its safety and efficacy have not been well studied in more advanced cases of CKD. We studied the safety and efficacy of escalating doses of febuxostat over a 24-week period in 70 patients with CKD stages 3b, 4 and 5, and we also observed the changes in blood pressure, estimated glomerular filtration rate (eGFR) and proteinuria following the reduction of sUA. Drug-related adverse events (AEs) occurred in only 5 out of 70 patients. All but one of the events were mild, and all five patients fully recovered. By 24 weeks, the reduction of sUA levels was >40% in CKD stage 3b and >50% in CKD stages 4 and 5. More than 70% of patients achieved target sUA levels of 6 mg dl(-1) or less. Multivariate analysis showed that a greater reduction in sUA with febuxostat was associated with an increase in eGFR and a tendency toward decreased proteinuria. Febuxostat was safe and efficacious in the treatment of CKD stages 3b-5.
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, St Marianna University School of Medicine, Kawasaki, Japan.
authors.forename: Yugo
authors.initials: Y
authors.lastname: Shibagaki
authors.affiliation: Division of General Medicine, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Iwao
authors.initials: I
authors.lastname: Ohno
authors.affiliation: Division of Kidney and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Hosoya
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, St Marianna University School of Medicine, Kawasaki, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kimura
mesh_terms: D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D023381:Endpoint Determination; D000069465:Febuxostat; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006074:Gout Suppressants / Q000009:adverse effects* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011507:Proteinuria / Q000188:drug therapy; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy*; D013844:Thiazoles / Q000009:adverse effects* / Q000627:therapeutic use*; D014527:Uric Acid / Q000097:blood
chemical_list: D006074:Gout Suppressants; D013844:Thiazoles; D000069465:Febuxostat; D014527:Uric Acid