Anemia is associated with increased risk of contrast‑induced acute kidney injury: A Systematic Review and Meta-analysis

Figures & data

Figure 1. PRISMA flow diagram of literature selection

Table 1. General characteristics of the included studies

Author(et.al),Year	Country	Study design	Period of research	Population(F/M) age(years)	Definition of anemia	Definition of CIN	OR/RR(95% CI)	Adjusted variables	NOS score
Chong2010 [13]	Singapore	Retrospective cohort study	May 2000 to April 2008	3036(654/2382) 57.4	Anemia was defined as serum Hb<11 g/dL	CIN was defined as ≥25% or ≥0.5 mg/dL increase from baseline Cr within 48 hours after PCI	2.49(1.66–3.74)	Age group, gender, race, hypertension, anemia, low BP, LVEF 50, diabetes (no diabetes, noninsulin-dependent diabetes, insulin-dependent diabetes), GFR, CK500, race, and indication for PCI	8
Li2013 [16]	China	Hospital-based case-control study	1 January 2008 and 31 October 2009	1026(404/622) 64 (29–81)	Anemia was defined as hemoglobin<120 g/l in women and <130 g/l in men.	Contrast-induced  nephropathy (CIN) was defined as the elevation of serum reatinine by ≥0.5 mg/dl or ≥25% occurring within 3 days after the intravascular administration of contrast medium, without an alternative etiology	2.352(1.395–3.453)	Age, sex, BMI, hypertension, hypercholesterolemia, LVEF, presence of diabetes mellitus, AMI, UAP, prior MI, baseline eGFR, amount of contrast agent administered, glucose level and hemoglobin level	7
Daisuke2014 [17]	Japan	Retrospective cohort study	April 2007 to April 2010	1954(443/1511) 69.1	Anemia was defined as a hemoglobin (Hb) level <10 g/dl/dl	CI-AKI was defined as an increase in serum creatinine of 0.5 mg/dl or 25% within 1 week from contrast-medium injection	2.31 (1.17–4.55)	Age, sex, CV/eGFR, prior CHF, multivessel disease, IABP, LVEF<40%, diuretic use, and Hb <10 g/dl	7
Kim2014 [10]	South Korea	Case-control study	September 2006 to December 2011	297(97/200)	NR	CI-AKI was defined as serum creatinine level either 25% or 0.5 mg/dl from baseline within 72 hours after contrast exposure	0.85(0.67–1.01)	Age, gender, body surface area, LV systolic dysfunction, clinical presentation, diabetes mellitus, type of contrast media, contrast V/CrCl >6.0, eGFR, serum hemoglobin, number of inserted stents, shock, PCI for left main (LM) coronary artery disease, and hydration before the procedure	6
Guo2015 [8]	China	Prospective cohort study	January 2010 to October 2013	1772(336/1436)	NR	Contrast-induced acute kidney injury was defined as an increase in serum creatinine of >0.5 mg/dL from the baseline within 48 to 72 hours of contrast exposure	1.959(1.036–3.704)	DM, males, LVEF<40%, emergent PCI, P_MI, age>60 mL/min/1.73 m^2, diiuretic usage, hyperuricemia	7
Kurtul2015 [15]	Turkey	Case-control study	March 2012 to August 2014	814(256/558) 61 ± 12	NR	Contrast-induced  acute kidney injury was defined as an increase in serum creatinine level of 25% or 0.5 mg/dL above the baseline value which occurs within 48 to 72 hours after the procedure	0.788 (0.650–0.956)	Age, women, diabetes mellitus, current smoker, heart rate, left ventricular ejection fraction, white blood cell count, hemoglobin, estimated glomerular filtration rate, total cholesterol, uric acid, creatine kinase myocardial band, high-sensitivity C-reactive protein, procalcitonin, SYNTAX score and total time of precedure	6
Shacham2015 [21]	Israe	Retrospective cohort study	January 2008 to December 2013	1248(237/1011) 61 ± 13	Anemia was defined as hemoglobin < 12 g/dL in women and < 13 g/dL in men, according to the World Health Organization criteria	AKI was determined using the AKI Network criteria, and defined as an sCr increase > 0.3 g/dL, compared with admission sCr	1.76(1.02–3.02)	Age, sex, hypertension, diabetes mellitus, left ventricular ejection fraction, admission eGFR, critical state, time to coronary reperfusion, and admission hemoglobin level or the presence of anemia	8
Banda2016 [18]	South Africa	Prospective cohort study	1 July 2014 to 30 July 2015	371(161/210) 49.3 (15.9)	Anemia was defined as serum hemoglobin (Hb) < 11 g/dL	CIN was defined as a serum creatinine increase of >25% from baseline or an absolute increase of 44 µmol/L assessed within 48–72 hours post contrast media administration as per the 2011 updated European Society of Urogenital Radiology (ESUR) guidelines	1.71(1.01–2.87)	Age, gender, albumin level and baseline eGFR	8
Hsieh2016 [14]	Taiwan, China	Case-control study	July 2003 to June 2015	377(108/269) 36.3 ± 17.4	Anemia due to acute bleeding (initial Hb < 11 g/dL)	CIN was defined as the relative (25%) or absolute (0.5 mg/dL) increase in serum creatinine within 48 h after contrast administration	3.16(1.46–6.81)	Body mass index, Injury Severity Score, Spleen Injury Scale, Large hemoperitoneum, Splenectomy, Splenectomy	7
Sato2016 [20]	Japan	Prospective cohort study	November 2011 to September 2013	853(198/655)	Anemia was defined by the World Health Organization criteria as a hemoglobin level < 13 g/dl for men and <12 g/dl for women	CIN was defined as increase in serum creatinine (SCr) ≥ 0.5 mg/dL or ≥25% from baseline between 48 and 72 h after exposure to contrast	1.94(1.08–3.61)	Age, male sex, diabetes mellitus, hypertension, CIN, SCr and anemia	9
Grossman2017 [19]	America	Prospective cohort study	1 January 2010 and 31 December 2013	13,126(6015/7111)	NR	CIN was defined as an increase in serum creatinine from baseline to post-PVI peak creatinine ≥0.5 mg/dLwas defined as an increase in serum creatinine from baseline to post-PVI peak creatinine ≥0.5 mg/dL	2(1.6–2.6)	A history of diabetes, anemia, CHF, and a pre-procedural CCC < 60 mL/min	8
Liu2017 [11]	Taiwan, China	Retrospective cohort study	February 2007 to September 2012	206(56/150) 65(55–77)	Anemia was defined as hematocrit < 39% in men and < 36% in women	CIAKI was defined as: 1) an absolute elevation of serum creatinine > 0.5 mg/dl in patients with baseline serum creatinine 2.0 mg/dl, or 2) a relative increase of 25% from the baseline value in patients with baseline creatinine > 2.0 mg/dl within 96 hours after primary PCI was performed.	0.908(0.689–1.197)	Age, creatinine, hemoglobin, multi-vessel disease,	8
Sreenivasan2018 [9]	America	Case-control study	January 2012 to December 2016	2055(631/1424) 58.0 ± 12.5	Anemia was defined as baseline hemoglobin≤13 g/dL. mild (11.1 to 13.0 g/dL), moderat (9.1 to 11.0 g/dL) and severe (7.0 to 9.0 g/dL)	Defined AKI as 0.5 mg/dL increase in serum creatinine from baseline following coronary angiography	5.3(3.8–7.3)	Race/ethnicity, prior CKD, prior heart failure, diabetes mellitus, hypertension, intra-aortic balloon pump (IABP) use prior to or within 24 hours of procedure, presence of cardiogenic shock, acute coronary syndrome (ACS)	7

CIN = contrast induced/media-induced nephropathy; CI-AKI = contrast-induced acute kidney injury; CM = contrast media; NR = not reported; CI = confidence interval; DM = diabetes mellitus; LVEF = left ventricular ejection fraction; OR = odds ratio; HR = hazard ratio; PCI = percutaneous coronary intervention; sCr = serum creatinine; P_MI = previous myocardial infarction; CHF = congestive heart failure; CCC = calculated creatinine clearance; BSA = Body surface area; eGFR = Estimated glomerular filtration rate; WHO = world health organization; CKD = chronic kidney disease; NOS = Newcastle–Ottawa Scale.

Table 2. Methodological quality of included studies based on the Newcastle–Ottawa Scale* for assessing the quality of case-control and cohort studies

Case-control studies (n = 4)	Selection	Comparability (control for important factors or additional factor)	Exposure	Total
	Adequate definition of cases	Representativeness of cases	Selection of controls	Definition of controls		Ascertainment of exposure (blinding)	Same method of ascertainment for participants	Non-response rate
Li2013 [16]	☆	☆	-	☆	☆☆	☆	☆	-	7
Kim2014 [10]	-	☆	☆	☆	☆☆	-	☆	-	6
Kurtul2015 [15]	☆	☆	☆	-	☆	☆	☆	-	6
Hsieh2016 [14]	☆	☆	☆	☆	☆☆	-	☆	-	7
Sreenivasan 2018 [9]	☆	☆	☆	☆	☆☆	-	☆	-	7
Cohort studies (n = 9)	Selection	Comparability (control for important factors or additional factor)	Outcome
	Representativeness of exposed cohort	Selection of non-exposed cohort	Ascertainment of exposure	Outcome of interest not present at start of study		Assessment of outcome	Follow-up long enough for outcomes to occur^1	Adequacy of follow-up of cohorts^2	Total
Chong2010 [13]	☆	☆	☆	☆	☆☆	☆	☆	-	8
Daisuke2014 [17]	☆	☆	☆	☆	☆☆	☆	-	-	7
Guo2015 [8]	☆	☆	☆	☆	☆	☆	☆	-	7
Shacham2015 [21]	☆	☆	☆	☆	☆☆	☆	☆	-	8
Banda2016 [18]	☆	☆	☆	☆	☆☆	☆	☆	-	8
Sato2016 [20]	☆	☆	☆	☆	☆☆	☆	☆	☆	9
Grossman2017 [19]	☆	☆	☆	☆	☆☆	☆	☆	-	8
Liu2017 [11]	☆	☆	☆	☆	☆☆	☆	☆	-	8

*A study can be awarded a maximum of one star for each numbered item within the Selection and Exposure categories and maximum of two stars can be given for comparability. ¹ A cohort study with a follow-up time > 6 months was awarded one star.

²A cohort study with a follow-up rate > 75% was awarded one star.

Table 3. Subgroup analysis of association between anemia and contrast media-induced nephropathy based on various factors

Outcomes	Number of trials	OR/RR (95% CI)	Heterogeneity, I^2 (%)
Pooled results	13	1.82 (1.27–2.61)	92.5
Subgroup analyses based on study type
Cohort studies	8	1.77 (1.32–2.38)	73
Case-control studies	5	1.88 (0.89–3.96)	96.8
Subgroup analyses based on study design
Prospective studies	4	1.95 (1.60–2.37)	0
Retrospective studies	9	1.79 (1.11–2.89)	94.5
Subgroup analyses based on sample size
N ≥ 1000	7	2.48 (1.78–3.47)	76.8
N < 1000	6	1.17 (0.87–1.58)	79.3
Subgroup analyses based on quality of included studies (NOS)
≥8	6	1.70 (1.19–2.42)	79.6
<8	7	1.94 (1.05–3.58)	95.3
Subgroup analyses based on definition of anemia
Hb level	8	2.20 (1.21–4.00)	93.9
NR or Others	5	1.35 (0.88–2.07)	88.9
Subgroup analyses based on rergion
Asia	8	1.74 (1.17–2.59)	86
America	2	3.24 (1.24–8.41)	85
Other	3	1.28 (0.69–2.37)	95.5

OR = odds ratio; RR = relative ratio; CI = confidence interval; Hb = hemoglobin; NOS = Newcastle-Ottawa Scale; NR = not report.

Figure 2. Forest plot of association between anemia and contrast-induced acute kidney injury (CI-AKI) (OR, 1.82; 95% CI, 1.27–2.61)

Figure 3. Sensitivity analysis of association between anemia and CI-AKI: the result showed the pooled ORs were stable

Figure 4. Primary funnel plot for publication bias (a) (Egger`s test: P = 0.045); Adjusted funnel plot from trimming estimator and filled analysis for publication bias (Pooled OR, 1.57;95% CI, 1.10–2.25, P = 0.013)

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