Overview of Included Studies
| Author/Country | Population | Study Design | No. of Patients(Treatment/Control) | Baseline Characteristic* (Treatment/Control) | Treatment | Comparison | Period(weeks) | Primary Outcome |
|---|---|---|---|---|---|---|---|---|
| Siu, 2005 China28 | patients with chronic kidney disease | randomized controlled trial | 25/26 | uric acid (mg/dL): 9.75/5.88 Cr (mg/dL): 1.62/1.86 SBP (mm Hg): 138/135 DBP (mm Hg): 79/71 | allopurinol, 100 to 300 mg/day | no urate-lowering medical therapy | 48 | – 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 Japan29 | patients with stable compensated CHF | double-blind, placebo-controlled, randomized crossover study | 14/14 | uric acid (mg/dL): 10.2/10.2 | Benzbromarone 50 mg/day | placebo | 8 | – the change of BNP levels – change in echocardiographic parameters of left ventricle dimensions and LVEF |
| Kanbay, 2011 Turkey30 | patients with normal renal function | randomized, controlled trial | 30/37 | uric acid (mg/dL): 8.3/7.9†,‡ eGFR: 86.3/84.3 SBP (mm Hg):127.6/123.2 DBP (mm Hg): 75.1/75.6 | allopurinol 300 mg/day | no urate-lowering medical therapy | 16 | – endothelial dysfunction – BP – eGFR |
| Liu, 2015 China31 | patients with type 2 diabetes | randomized open parallel-controlled study | 88/88 | uric acid (μmol/L) : 433/432 eGFR: 90.1/90.1SBP (mm Hg): 121/121 DBP (mm Hg): 74/74 | allopurinol starting from 100 mg/day | no urate-lowering medical therapy | 144 | changes in the carotid IMT |
| Sircar, 2015 India32 | eastern India aged 18 to 65 years with CKD stages 3 and 4 | double-blind, randomized, parallel-group, placebo-controlled study | 45/48 | uric acid (mg/dL): 9.0/8.2 eGFR: 31.5/32.6 | febuxostat 40 mg/day | placebo | 24 | ≥10% decline in eGFR from baseline |
| Takir, 2015 Turkey33 | patients without a history of diabetes mellitus, kidney and liver disease | randomized, controlled trial | 40/33 | uric acid (mg/dL): 7.86/7.45 Cr (mg/dL): 0.9/1.07 | allopurinol 300 mg/day | no urate-lowering medical therapy | 12 | improvement in insulin resistance defined by homeostatic model assessment of insulin resistance |
| Beddhu, 2016 USA34 | overweight or obese adults with type 2 diabetic nephropathy | double-blinded randomized controlled trial | 37/39 | uric acid (μmol/L): 426/422 eGFR: 52.2/54.8SBP (mm Hg): 125.2/128.3DBP (mm Hg): 68.1/72.0 | febuxostat 80 mg/day | placebo | 24 | – adipose tissue TBARS and adiponectin concentrations – urinary transforming growth factor–β |
| Jalal, 2017 USA35 | ≥ 18 years of age with stage 3 CKD | double-blind, randomized, controlled trial | 39/41 | uric acid (mg/dL): 8.3/8.7 eGFR: 41.3/42.4 SBP (mm Hg): 127/130 DBP (mm Hg): 77.4/77.7 | allopurinol 300 mg/day (200 mg, 100 mg) | placebo | 12 | change in brachial artery flow-mediated Dilation |
| Kimura, 2018 Japan36 | patients with CKD stage 3 | randomizeddouble-blind, parallel-group, placebo-controlled trial | 219/222 | uric acid (mg/dL): 7.8/7.8eGFR: 45.2/44.9 SBP (mm Hg): 132.5/129.6 DBP (mm Hg): 77.9/77.3 | febuxostat (10 mg, 20 mg, 40 mg) | placebo | 108 | eGFR slope |
| Mukri, 2018 Malaysia37 | CKD stage 3 and 4 patients with diabetic nephropathy | open-label, randomized study | 47/46 | uric acid (μmol/L): 539.5/537.3 eGFR: 26.2/28.2 SBP (mm Hg): 141/146 DBP (mm Hg): 73.7/71.7 | febuxostat 40 mg/day | no urate-lowering medical therapy | 24 | slowing the eGFR decline |
| Kojima, 2019 Japan38 | elderly patients who had one or more risks for cerebral, cardiovascular, or renal disease | randomized open-label, blinded endpoint study | 537/533 | uric acid (mg/dL): 7.54/7.50 eGFR: 54.62/55.35 SBP (mm Hg): 132.9/132.3 DBP (mm Hg): 73.5/73.6 | febuxostat (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 USA39 | patients with CKD stage 3 | double-blind randomized placebo-controlled study | 39/41 | eGFR: 41.4/41.7 SBP (mm Hg): 127/129 DBP (mm Hg): 77/77 | allopurinol 300 mg/day | placebo | 12 | – change of albumin-creatinine ratio – neutrophil gelatinase-associated lipocalin – kidney injury molecule 1 transforming growth factor β1 |
| Tanaka, 2020 Japan40 | adults with maximum IMT of the CCA ≥ 1.1 mm at screening | randomized, open-label, blinded-endpoint clinical trial | 257/257 | uric acid (mg/dL): 7.76/7.73 eGFR: 56.26/57.12 SBP (mm Hg): 128.9/127.3 DBP (mm Hg): 73.3/74.18 | febuxostat (10-60 mg/day) | no urate-lowering medical therapy | 96 | – 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.