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Table 1 Characteristics of 11 studies included in the meta-analysis

From: Serum uric acid and cardiovascular mortality in chronic kidney disease: a 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

  1. Conversion factors for units: serum uric acid in mg/dl to umol/l, ×59.48
  2. 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