Table 1.

Characteristics of studies included in the meta-analysis

Authors (year)	Study period	Country	Study design	Sample size	Mean age (y)	Percentage of Male (%)	Inclusion criteria	Definition of hyperuricemia or grouping according to SUA	Definition of AKI	Mean baseline eGFR in HUA group (ml/min/1.73 m2)	Conclusions
Shacham, et al. (2016) [48]	2008–2015	Israel	Retrospective cohort	1372	62 ± 12	85	Acute STEMI patients requiring PCI	<4.7 mg/dl, 4.8–5.6 mg/dl, 5.7–6.6 mg/dl, >6.7 mg/dl	A rise in sCr >0.3 mg/d above the admission sCr within 48 h	79 ± 19, 75 ± 17, 70 ± 11, 63 ± 20 for 4 groups respectively	Elevated UA levels are an independent predictor of AKI
Cheungpasitporn, et al. (2016) [49]	2011–2013	USA	Retrospective cohort	1435	62 ± 16	60.3	All hospitalized adult patients without ESRD and AKI at presentation and trauma	<3.4 mg/dl, 3.4–4.5 mg/dl, 4.5–5.8 mg/dl, 5.8–7.6 mg/dl, 7.6–9.4 mg/dl, >9 mg/dl	An increase in sCr ≥0.3 mg/dL within 48 h or ≥1.5 times baseline within 7 days after admission date	89.5 ± 20.6, 88.1 ± 21.9, 79.3 ± 24.5, 71.7 ± 24.8, 58.6 ± 22.3, 53.2 ± 21.8 for 6 groups respectively	Elevated admission SUA was associated with an increased risk for in-hospital AKI
Otomo, et al. (2015) [6]	1981–2011	Japan	Retrospective cohort	59,219	58.6 ± 17.9	48.4	All hospitalized patients	The first stratum: SUA ≤2.0 mg/dL; the 12th stratum: SUA >7.0 mg/dL, with SUA levels in each succeeding stratum increasing by increments of 0.5 mg/dL	An increase ≥0.3 mg/dL in the sCr level within 48 h; or ≥1.5 times baseline within the prior 7 days; or urine volume of 0.5 mL/kg/h within 6 h	102 ± 50, 99 ± 44, 96 ± 45, 93 ± 38, 88 ± 31, 86 ± 34, 81 ± 28, 79 ± 29, 76 ± 28, 73 ± 28, 70 ± 27, 59 ± 34 for 6 groups respectively	SUA level could be an independent risk factor for AKI development in hospitalized patients
Liang, et al. (2015) [50]	2009–2014	China	Prospective cohort	59	37.3 ± 10.6	NR	Severe burn	NR	An absolute anincrease in sCr > 0.3 mg/dl from baseline within 48 h after injury	NR	Elevated SUA after injury due to hypoxia is closely correlated with early AKI after severe burns
Lee, et al. (2015) [7]	2006–2011	Korea	Retrospective cohort	2,185	63.6 ± 9.1	74.7	All patients undergoing CABG	NR	An increase in sCr of ≥0.3 mg/dL or ≥150% from baseline within the first 48 h after operation	NR	Preoperatively Elevated SUA was significantly associated with AKI and improved the ability to predict the development of AKI in patients undergoing CABG
Lazzeri, et al. (2015) [51]	2006–2013	Italy	Prospective cohort	329	77.2 ± 10.0	53.8	STEMI patients submitted to primary PCI	SUA ≤ 5.9 mg/dl, 6.0–7.4 mg/dl, >7.4 mg/dl	An absolute increase in sCr level of 0.3 mg/dl or more, or a relative increase in sCr level of 50% or more during the ICCU stay	42.8 ± 14.3, 42.5 ± 13.4, 40.8 ± 12.2 for 3 groups respectively	Uric acid helps in identifying a subset of patients at a higher risk of AKI and 1-year mortality.
Gaipov, et al. (2015) [52]	2011–2012	Turkey	Prospective cohort	60	56.7 ± 16.4	70.0	Patients undergoing cardiac surgery	NR	An increase in sCr by 0.3 mg/dL within 48 h or increase in sCr to 1.5 times baseline	NR	Uric acid seems to predict the progression of AKI and RRT requirement in patients underwent cardiac surgery better than NGAL
Barbieri, et al. (2015) [8]	2007–2011	Italy	Retrospective cohort	1,950	72.1 ± 8.7	NR	Patients undergoing coronary angiography and /or angioplasty with GFR ≤ 89 ml/min	SUA ≤ 5.5 mg/dL; 5.6–7.0 mg/dL; ≥7.0 mg/dL	An absolute ≥0.5 mg/dl or a relative ≥25% increase in the sCr level at 24 or 48 h after the procedure	NR	Elevated SUA level is independently associated with an increased risk of CIN
Guo, et al. (2015) [53]	2010–2013	China	Prospective cohort	1772	64.43 ± 11.35	76.5	Patients who underwent PCI	SUA > 7 mg/dL (417 μmol/L) in males and >6 mg/dL (357 μmol/L) in females.	an increase in sCr of >0.5 mg/dL from the baseline within 48–72 h of contrast exposure	71.08 ± 24.70	Hyperuricemia is associated with a risk of CI-AKI. Long-term mortality after PCI was higher in those with hyperuricemia than with normouricemia after adjusting.
Joung, et al. (2014) [54]	2011–2012	Korea	Retrospective cohort	1,094	63.0	62.2	Patients undergoing cardiovascular surgery	SUA > 6.5 mg/dL (preoperative) (6.0 mg/dL in women and 7.0 mg/dL in men)	An increase ≥0.3 mg/dL in the sCr level or ≥1.5 times baseline within 48 h	NR	Preoperative elevated serum uric acid is an independent risk factor for AKI in patients undergoing cardiovascular surgery.
Xu, et al. (2014) [55]	2005–2011	China	Retrospective cohort	936	65.2 ± 4.2	54.3	Old patients (≥60 years) undergoing CPB	SUA ≤ 384.65; 384.66–476.99; ≥477.00 μmol/L (males) SUA ≤ 354.00; 354.01–437.96; ≥437.97 μmol/L (females)	An increase in sCr ≥150% from baseline within the first 7 days after operation	73.8 ± 17.2, 69.3 ± 14.2, 61.5 ± 15.8 for 3 groups respectively	Pre-operative elevated uric acid is an independent risk factor of AKI after cardiac surgery in elderly patients
Liu, et al. (2013) [56]	2010–2011	China	Prospective cohort	788	62.8 ± 11.3	78.6	Patients undergoing PCI	SUA >7 mg/dL in males and >6 mg/dL in females	An increase in sCr of ≥ 0.5 mg/dL above the baseline value within 48–72 h after PCI	*Creatinine Clearance: 65 ± 24 ml/min	Hyperuricemia was significantly associated with the risk of CI-AKI in patients with relatively normal serum creatinine after PCI
Lapsia, et al. (2012) [57]	2004–2008	USA	Retrospective cohort	190	63.9 ± 0.9	62.1	Patients undergoing cardiovascular surgery	SUA ≥7 mg/dL	An absolute increase in sCr of ≥ 0.3 mg/dL from baseline within 48 h after surgery	47.6 ± 1.8	Preoperative SUA was associated with increased incidence and risk for AKI
Ejaz, et al. (2012) [58]	NR	USA	Prospective cohort	100	61.4 ± 1.4	60	Patients undergoing cardiac surgery with eGFR > 30 ml/min/1.73 m2	SUA < 4.53 mg/dL, 4.53–5.77 mg/dL, > 5.77 mg/dL	An absolute increase in sCr ≥ 0.3 mg/dL from baseline within 48 h after surgery	NR	Post-operative SUA is associated with an increased risk for AKI and compares well to conventional markers of AKI
Park, et al. (2011) [59]	2006–2009	Korea	Retrospective cohort	1,247	64.3 ± 11.9	62.3	Patients undergoing PCI	SUA ≥7.0 mg/dl for males and ≥ 6.5 mg/dl for females.	An increase in sCr of ≥0.5 mg/dl or ≥50% over baseline within 7 days of PCI	NR	Hyperuricemia is independently associated with an increased risk of in-hospital mortality and AKI in patients treated with PCI
Kim, et al. (2011) [60]	2007–2008	Korea	Retrospective cohort	247	46.1 ± 13.7	52	Acute PQ intoxication	SUA ≥7.3 mg/dL in men or ≥5.3 mg/dL in women	An increase in sCr of ≥0.3 mg/dL or ≥150% from baseline within 48 h after admission	NR	Baseline serum uric acid level might be a good clinical marker for patients at risk of mortality and AKI after acute PQ intoxication
Ben-Dov, I. Z., et al. (2011) [61]	1976–1979	Israel	Retrospective cohort	2449	58.8	50 ± 6	Patients in Lipid Research Clinic cohort	>6.5 mg/dL in men and >5.3 mg/dL in women	NR	93 ± 18 in men and women	SUA was found to be a strong predictor of acute renal failure
Toprak et al. (2006) [62]	2004–2005	Turkey	Prospective cohort	266	58.9 ± 7.4	61%	Nonemergency diagnostic coronary angiography with Scr > 1.2 mg/dl	>7 mg/dl in men and 6.5 mg/dl in women.	An increase of ≥25% in sCr over baseline within 48 h of coronary angiography	55.26 ± 13.7	Patients with hyperuricemia are at risk of developing CIN.

Abbreviations: SUA serum uric acid, sCr serum creatintine, AKI acute kidney injury, CABG Coronary Artery Bypass Grafting, STEMI ST-elevation myocardial infarction, PCI percutaneous coronary intervention, NGAL neutrophil gelatinase-associated lipocalin, GFR glomerular filtration rate, eGFR estimated glomerular filtration rate, CIN contrast-induced nephropathy, CI-AKI contrast-induced acute kidney injury, PQ paraquat, NR not reported