Table 1.

Overview of Included Studies

Author/CountryPopulationStudy DesignNo. of Patients(Treatment/Control)Baseline Characteristic* (Treatment/Control)TreatmentComparisonPeriod(weeks)Primary Outcome
Siu, 2005 China28patients with chronic kidney diseaserandomized controlled trial25/26uric acid (mg/dL): 9.75/5.88 Cr (mg/dL): 1.62/1.86 SBP (mm Hg): 138/135 DBP (mm Hg): 79/71allopurinol, 100 to 300 mg/dayno urate-lowering medical therapy48– stable kidney function with less than 40% increase in serum creatinine level
– impaired renal function with creatinine level increase greater than 40% of baseline value
Ogino, 2010 Japan29patients with stable compensated CHFdouble-blind, placebo-controlled, randomized crossover study14/14uric acid (mg/dL): 10.2/10.2Benzbromarone 50 mg/dayplacebo8– the change of BNP levels
– change in echocardiographic parameters of left ventricle dimensions and LVEF
Kanbay, 2011 Turkey30patients with normal renal functionrandomized, controlled trial30/37uric acid (mg/dL): 8.3/7.9, eGFR: 86.3/84.3 SBP (mm Hg):127.6/123.2 DBP (mm Hg): 75.1/75.6allopurinol 300 mg/dayno urate-lowering medical therapy16– endothelial dysfunction
– BP
– eGFR
Liu, 2015 China31patients with type 2 diabetesrandomized open parallel-controlled study88/88uric acid (μmol/L) : 433/432 eGFR: 90.1/90.1SBP (mm Hg): 121/121 DBP (mm Hg): 74/74allopurinol starting from 100 mg/dayno urate-lowering medical therapy144changes in the carotid IMT
Sircar, 2015 India32eastern India aged 18 to 65 years with CKD stages 3 and 4double-blind, randomized, parallel-group, placebo-controlled study45/48uric acid (mg/dL): 9.0/8.2 eGFR: 31.5/32.6febuxostat 40 mg/dayplacebo24≥10% decline in eGFR from baseline
Takir, 2015 Turkey33patients without a history of diabetes mellitus, kidney and liver diseaserandomized, controlled trial40/33uric acid (mg/dL): 7.86/7.45 Cr (mg/dL): 0.9/1.07allopurinol 300 mg/dayno urate-lowering medical therapy12improvement in insulin resistance defined by homeostatic model assessment of insulin resistance
Beddhu, 2016 USA34overweight or obese adults with type 2 diabetic nephropathydouble-blinded randomized controlled trial37/39uric acid (μmol/L): 426/422 eGFR: 52.2/54.8SBP (mm Hg): 125.2/128.3DBP (mm Hg): 68.1/72.0febuxostat 80 mg/dayplacebo24– adipose tissue TBARS and adiponectin concentrations
– urinary transforming growth factor–β
Jalal, 2017 USA35≥ 18 years of age with stage 3 CKDdouble-blind, randomized, controlled trial39/41uric acid (mg/dL): 8.3/8.7 eGFR: 41.3/42.4 SBP (mm Hg): 127/130 DBP (mm Hg): 77.4/77.7allopurinol 300 mg/day (200 mg, 100 mg)placebo12change in brachial artery flow-mediated Dilation
Kimura, 2018 Japan36patients with CKD stage 3randomizeddouble-blind, parallel-group, placebo-controlled trial219/222uric acid (mg/dL): 7.8/7.8eGFR: 45.2/44.9 SBP (mm Hg): 132.5/129.6 DBP (mm Hg): 77.9/77.3febuxostat (10 mg, 20 mg, 40 mg)placebo108eGFR slope
Mukri, 2018 Malaysia37CKD stage 3 and 4 patients with diabetic nephropathyopen-label, randomized study47/46uric acid (μmol/L): 539.5/537.3 eGFR: 26.2/28.2 SBP (mm Hg): 141/146 DBP (mm Hg): 73.7/71.7febuxostat 40 mg/dayno urate-lowering medical therapy24slowing the eGFR decline
Kojima, 2019 Japan38elderly patients who had one or more risks for cerebral, cardiovascular, or renal diseaserandomized open-label, blinded endpoint study537/533uric acid (mg/dL): 7.54/7.50 eGFR: 54.62/55.35 SBP (mm Hg): 132.9/132.3 DBP (mm Hg): 73.5/73.6febuxostat (10-40 mg/day)non-febuxostat groupno treatment or allopurinol 100 mg (27.2% patients)144– fatal and non-fatal cerebral, cardiovascular and renal
– death other than cerebral or cardiorenal vascular disease
Perrenoud, 2020 USA39patients with CKD stage 3double-blind randomized placebo-controlled study39/41eGFR: 41.4/41.7 SBP (mm Hg): 127/129 DBP (mm Hg): 77/77allopurinol 300 mg/dayplacebo12– change of albumin-creatinine ratio
– neutrophil gelatinase-associated lipocalin
– kidney injury molecule 1 transforming growth factor β1
Tanaka, 2020 Japan40adults with maximum IMT of the CCA ≥ 1.1 mm at screeningrandomized, open-label, blinded-endpoint clinical trial257/257uric acid (mg/dL): 7.76/7.73 eGFR: 56.26/57.12 SBP (mm Hg): 128.9/127.3 DBP (mm Hg): 73.3/74.18febuxostat (10-60 mg/day)no urate-lowering medical therapy96– percentage change from baseline to 24 months in mean IMT of the CCA
  • Abbreviations: BNP, brain natriuretic peptide; BP, blood pressure; CCA, common carotid artery; CHF, chronic heart failure; CKD, chronic kidney disease; CRP, C-reactive protein; CV, cardiovascular; DBP, diastolic blood pressure; DN, diabetic nephropathy; eGFR, estimated Glomerular filtration rate; FMD, Flow-mediated dilation; IMT, intima-media thickness; IL-6, interleukin-6; LVEF, left ventricular ejection fraction; MCP-1, monocyte chemotactic protein-1; Ox-LDL, oxidized low-density lipoprotein; NF-kB, nuclear factor-kappa B; SBP, systemic blood pressure; TBARS, thiobarbituric acid-reducing substances; UAER, urinary albumin excretion rate.

  • * Values are expressed as mean.

  • The unit of eGFR is mL/min/1.73 m2.

  • Values are expressed as median.