Table 1.
Characteristics of 11 studies included in the meta-analysis
| Author, year | Study design | Population | Patients (n) | Men (%) | Diabetes (%) | Age (years) | Uric acid (mg/dl) | Follow-up | Cardiovascular mortality events and definition (n) | Comparison | Adjust HR (95%CI) | Adjustments | Quality score |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Madero, 2009 [8] | RCT | United States, MDRD, CKD3–4 | 838 | 39 | 5 | 52 ± 12 | 7.63 ± 1.66 | Median 10 years | 127 CV mortality was defined as death resulting from CVD (International classification of diseases, ninth revision [ICD-9] codes 390 to 459) |
Per 1 mg/dl increase Tertile 3 vs. tertile 1 8.4–15.6 mg/dl vs. 1.7–6.9 mg/dl |
1.16 (1.01–1.33) 1.47 (0.90–2.39) |
Age, gender, blood pressure, protein diet randomization assignments, history of CVD, DM, BMI, systolic blood pressure, HDL-C, log-transformed C-reactive protein, GFR, albumin, diuretic, allopurinol. | 3 |
| Latif, 2011 [17] | PCS | DOPPS, HD | 4637 | 58.2 | 24.5 | Mean 58–64 | Mean 6.97 | Median 23 months | NA CV mortality was defined as death resulting from acute myocardial infarction, atherosclerotic heart disease, cardiomyopathy, cardiac arrhythmia, cardiac arrest, congestive heart failure, cerebrovascular accident including intracranial hemorrhage, ischemic brain damage and anoxic encephalopathy |
Per 1 mg/dl increase ≦8.2 mg/dl vs. > 8.2 mg/dl |
0.92 (0.86,0.99) 1.54 (1.15–2.07) |
Age, black race, gender, BMI, years with ESRD, albumin-corrected calcium, albumin, ferritin, creatinine, phosphorus, allopurinol, 14 comorbid conditions, study phase and facility | 5 |
| Kanbay, 2012 [9] | RCS | Turkey, CKD 3–5 |
303 | 49.8 | 23.4 | Mean 47–53 | NA | Median 39 months | 33 CV mortality was defined as death resulting from coronary heart disease, sudden death, stroke and complicated peripheral vascular disease |
Per 1 mg/dl increase | 2.819 (1.783–4.458) | Age, gender, eGFR, DM, smoking, hypertension, LDL, systolic blood pressure, hsCRP, HOMA-IR index, FMD, NMD | 6 |
| Kuo, 2013 [16] | RCS | Taiwan, CKD | 13,059 | NA | NA | NA | NA | Median 4.6 years | NA CV mortality was defined as death resulting from cardiovascular disease (ICD-9 codes: 390.x-459.x) |
9.0–10.9 mg/dl vs. 5.0–6.9 mg/dl ≧11.0 mg/dl vs. 5.0–6.9 mg/dl |
1.42 (1.11–1.81) 1.65 (1.22–2.24) |
Age, gender, eGFR, fasting glucose, total cholesterol and history of hypertension, DM, CHD, stroke, heart failure. | 6 |
| Yin, 2013 [20] | RCS | China, CKD undergoing DES | 1132 | 71.7 | 33.6 | 67.7 ± 7.8 | 7.8 ± 1.9 | Median 38.5 months | 50 CV mortality was defined as death resulting from coronary artery disease, cardiac arrhythmia, congestive heart failure, sudden death |
Quartile 4 vs. quartile 1 > 8.98 mg/dl vs. < 6.46 mg/dl |
0.84 (0.37–1.89) | Age, gender, DM, eGFR, left ventricular ejection, proteinuria, AMI, incomplete revascularization | 7 |
| Dong, 2014 [19] | RCS | China, SSOP, PD | 2193 | 49 | 37.7 | 58.1 ± 15.5 | 6.41 ± 1.87 | Median 26.5 months | 231 CV mortality was defined as death resulting from myocardial infarction, congestive heart failure, cerebral bleeding, cerebral infarction, arrhythmia, peripheral arterial disease and sudden death |
Per 1 mg/dl increase Gender-specific Tertile 3 vs. tertile 1 Men: 7.39–16.7 mg/dl women: 6.66–8.08 mg/dl vs. Men: 2.09–5.79 mg/dl women: 1.74–5.37 mg/dl |
1.04 (0.89,1.20) 1.35 (0.74,2.46) |
Age, residual renal function, albumin, hemoglobin, phosphate, C-reactive protein, history of CVD, DM, BMI, mean arterial pressure, LDL-C, center size, gender-adjusted only SUA as continuous variable | 7 |
| Miyaoka, 2014 [18] | RCS | Japan, CKD2–4 | 551 | 59.3 | 10 | 58.5 | 6.57 ± 1.35 | 6 years | 19 CV mortality was defined as death resulting from myocardial infarction, congestive heart failure. |
Tertile 3 vs. tertile 1 7.2–12.4 mg/dl vs. 3.0–5.8 mg/dl Hyperuricemia vs. normouricemia Hyperuricemia (> 7.0 mg/dl or with allopurinol) |
1.042 (0.139–7.831) 0.274 (0.103–0.731) |
Gender, smoking status, history of CVD, systolic blood pressure, HDL-C, triglyceride, hemoglobin, C-reactive protein (log), eGFR, proteinuria (log), etiology of kidney disease, diuretics, allopurinol Gender, smoking status, CVD, HDL-C, triglyceride, hemoglobin, C-reactive protein (log), eGFR, proteinuria (log), etiology of kidney disease, diuretics, allopurinol |
8 |
| Beberashvili, 2015 [30] | PCS | Isreael, MHD | 261 | 61.3 | 59 | 68.6 ± 13.6 | 5.76 ± 1.16 | 2 years | 31 CV mortality was defined as death resulting from coronary heart disease, sudden death, stroke, or complicated peripheral vascular disease. |
Per 1 mg/dl increase | 0.53 (0.33–0.86) | Age, gender, vintage, Kt/v, DM, comorbidity index, smoking, systolic blood pressure, waist hip rate, phosphorus, creatinine, residual renal function, malnutrition inflammation score, interleukin-6 | 7 |
| Hsieh, 2015 [31] | RCS | Taiwan CKD 3–5 |
2408 | 56.9 | 38.3 | 65.7 ± 12.6 | 7.73 ± 1.78 | Median 3.03 years | 143 CV mortality was defined as death resulting from coronary artery disease, cerebrovascular or peripheral vascular disease |
Per 1 mg/dl increase | 1.16 (0.92–1.32) | Age, gender, BMI, DM, hypertension, cardiovascular disease, gout, glycated hemoglobin, cholesterol, triglyceride, BUN, eGFR, GPT, albumin, Ca × P, white blood cell count, hemoglobin, proteinuria, diuretics, hypouricemic agents, erythropoiesis stimulating agents, ACE inhibitor and angiotensin II receptor blocker | 7 |
| Xia, 2016 [10] | PCS | China, PD | 1278 | 58.8 | 25.7 | 47.6 ± 15.0 | 7.2 ± 1.4 | Median 30.7 months | 126 CV mortality was defined as death resulting from acute myocardial infarction, cardiac arrhythmia, cardiac arrest, congestive heart failure, cerebrovascular accident, and peripheral vascular disease. |
Per 1 mg/dl increase Gender-specific Tertile 3 vs. tertile 1 DM Men: 7.1–13.8 mg/dl, women: 6.9–12.6 mg/dl vs. Men: 1.5–5.6 mg/dl, women: 1.2–5.4 mg/dl. NDM Men: 7.1–13.8 mg/dl, women: 6.9–12.6 mg/dl vs. Men: 1.5–5.6 mg/dl, women: 1.2–5.4 mgj/dl |
1.42 (1.13–1.79) DM Men 1.12 (0.78–1.61) DM Women 1.41 (1.09–1.82) NDM Men 1.24 (0.85–1.82) NDM Women 2.26 (1.14–4.48) DM 3.07 (1.54–6.08) NDM |
Age, BMI, hypertension, CVD, hemoglobin, albumin, phosphorus, serum creatinine, HDL-C, residual renal function, log-transformed high-sensitive C-reactive protein, glycated hemoglobin, use of allopurinol, and use of ACE inhibitor or angiotensin receptor blocker. Gender-adjusted only SUA as continuous variable. Glycated hemoglobin-adjusted on in DM. | 8 |
| Li, 2016 [32] | PCS | China, CKD 3–5 | 421 | NA | NA | NA | NA | Median 3.9 years | NA | Tertile 4 vs. tertile 1 7.29–18.88 mg/dl vs ≤ 5.08 mg/dl |
0.72 (0.28,1.81) | Age, gender, leisure-time physical activity, smoking, alcohol drinking, occupation, BMI, SBP, DBP, LDL-C, duration of CAD, type of CAD, history of diabetes, history of heart failure, coronary artery stenosis degree on coronary angiography, use of antidiabetic, cholesterol-lowering or antiplatelet drugs, use of diuretics, β-blockers and antihypertensive drugs | 6 |
Conversion factors for units: serum uric acid in mg/dl to umol/l, ×59.48
Abbreviations: AMI acute myocardial infarction, BMI body mass index, CAD coronary artery disease, CV cardiovascular, CVD cardiovascular disease, CHD coronary heart disease, CKD chronic kidney disease, DBP diastolic blood pressure, DM diabetes mellitus, DOPPS The Dialysis Outcome and Practice Patterns Study, DES drug-eluting stent, eGFR estimated glomerular filtration rate, ESRD end-stage renal disease, FMD flow-mediated dilatation, HD hemodialysis, HDL-C high density lipoprotein cholesterol, HOMA-IR homeostasis model assessment-insulin resistance, hsCRP high sensitivity C reactive protein, LDL-C low density lipoprotein cholesterol, MHD maintenance hemodialysis, MDRD Modification of Diet In Renal Disease, NDM nondiabetes, NMD nitroglycerine-mediated dilatation, NA not available, PD peritoneal dialysis, SBP systolic blood pressure, SSOP Socioeconomic Status on the Outcome of Peritoneal Dialysis, SUA serum uric acid, RCT randomized controlled trial, PCS prospective cohort study, RCS retrospective cohort study