Methods
CKD, malignancy, infections, hypersensitivity, acute kidney injury
INFILTRATION, ADVERSE EVENTS, DISEASE, ASYMPTOMATIC HYPERURICEMIA, INFECTIONS, DISEASES, EVENTS, SECONDARY, CHRONIC KIDNEY DISEASE, HYPERSENSITIVITY, COMPLICATIONS, ENDOTHELIAL DYSFUNCTION
The study comprised a randomized controlled trial comparing the efficacy between febuxostat and control groups. The study was conducted among patients with CKD treated at Phramongkutklao Hospital between 31 January 2018 and 1 February 2019, with all subjects selected using inclusion criteria. Patients were randomized in blocks of four and allocation concealment, then divided in two groups as shown in Fig. Flow chart of study.The inclusion criteria included patients with CKD stages III to IV with asymptomatic hyperuricemia, age of 18 years or older, stable dose of all medications including ACEIs or ARBs for blood pressure control at least three months before enrolling and stable renal function within three months before the study. The exclusion criteria comprised active infections, acute kidney injury, advanced malignancy, serious disease, history of hypersensitivity to febuxostat and hospitalization within three months. Based on previous study results, to give 80% power with a two-sided significance level of 0.05 to detect a difference in serum asymmetric dimethylarginine (ADMA) as biomarkers of endothelial dysfunction, a sample size of 38 per treatment group was required to meet the superiority criteria between the febuxostat and placebo groups. Assuming a withdrawal rate of 10%, the target number of patients should be at least 42 in each groupThe data collected before and after in this study, contained relevant information on CKD including diagnostic criteria, complications of disease and other underlying diseases. The history of medications including antihypertensive drugs and physical examination were recorded. The laboratory tests including serum uric acid, blood urea nitrogen, creatinine, calculation of estimated glomerular infiltration rate (GFR) using the 2009 Chronic Kidney Disease Epidemiology Collaboration Equation (CKD-EPI), total cholesterol, low-density lipoprotein and high-density lipoprotein were noted. Participants would receive serum testing for ADMA and high sensitivity C-reactive protein (CRP) by enzyme linked immunosorbent assay. Urine albumin creatinine ratio (UACR) was measured by immunonephelometric assay method after receiving intervention. Ankle brachial index (ABI) was evaluated at baseline using an automatic device (VaSera VS-1000, Fukuda Denshi Co. LTD, Tokyo, Japan). ABI reflected the resistance or compliance of the aorta, femoral artery and tibial artery.The primary outcome was the change of serum ADMA and renal function after eight weeks in the febuxostat group, compared with that of the control group. The secondary outcome was the improving level of UACR after eight weeks. Any adverse events considered to be related to the use of febuxostat were recorded during the study, and any decision was made by the attending physicians during the study. For serious events, febuxostat was discontinued.