# Hydration Strategies for Preventing Contrast-Induced Acute Kidney Injury: A Systematic Review and Bayesian Network Meta-Analysis

Authors: Qiuping Cai; Ran Jing; Wanfen Zhang; Yushang Tang; Xiaoping Li; Tongqiang Liu
Journal: Journal of Interventional Cardiology
 (2020)

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## Abstract

Aims. Many previous studies have examined the effect of different hydration strategies on prevention of contrast-induced acute kidney injury (CI-AKI), but the optimal strategy is unknown. We performed a network meta-analysis (NWM) of these previous studies to identify the optimal strategy. Methods and Results. Web of Science, PubMed, OVID Medline, and Cochrane Library were searched from their inception dates to September 30, 2018. Randomized controlled trials (RCTs) were selected based on strict inclusion criteria, and a Bayesian NWM was performed using WinBUGS V.1.4.3. We finally analyzed 60 eligible RCTs, which examined 21,293 patients and 2232 CI-AKI events. Compared to intravenous 0.9% sodium chloride (reference), intravenous sodium bicarbonate (OR [95% CI]: 0.74 [0.57, 0.93]), hemodynamic guided hydration (0.41 [0.18, 0.93]), and RenalGuard guided hydration (0.32 [0.14, 0.70]) significantly reduced the occurrence of CI-AKI. Oral hydration and intravenous 0.9% sodium chloride were each noninferior to no hydration in preventing CI-AKI. Intravenous 0.9% sodium chloride, sodium bicarbonate, and hemodynamic guided hydration were each noninferior to oral hydration in preventing CI-AKI. Based on surface under the cumulative ranking curve values, the RenalGuard system was best (0.974) and hemodynamic guided hydration was second best (0.849). Conclusion. There was substantial evidence to support the use of RenalGuard or hemodynamic guided hydration for preventing CI-AKI in high-risk patients, especially those with chronic kidney disease or cardiac dysfunction.


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## Body

## 1. Introduction

Contrast-induced acute kidney injury (CI-AKI), also referred to as contrast-induced nephropathy (CIN), is an iatrogenic complication that can occur following intravascular administration of iodinated contrast medium (CM) prior to radiography. CI-AKI is the third leading cause of hospital-acquired acute renal injury (AKI) [1]. CI-AKI has a low incidence in the general population, but it has a significant incidence in patients with certain risk factors. Moreover, the occurrence of CI-AKI following cardiac catheterization procedures is associated with an in-hospital mortality of 20%, a 1-year mortality of up to 66%, and an even higher mortality in patients who require dialysis [2, 3]. However, even if patients with high risk of CI-AKI can be identified a priori, no known pharmaceutical treatment can effectively prevent or treat CI-AKI.Guidelines recommend intravascular hydration to prevent CI-AKI [4, 5], and there are several specific hydration strategies, but researchers have not yet established an optimal strategy [6–9]. Notably, recent randomized controlled trials (RCTs) have led to doubts about the effectiveness of various hydration strategies in prevention of CI-AKI. For example, Nijssen et al. [10] conducted an RCT with 660 high-risk patients and found that no prophylaxis was noninferior or cost-saving relative to intravenous hydration. Weisbord et al. [11] enrolled 5177 high-risk patients and reported no benefit of intravenous sodium bicarbonate relative to normal saline. Another RCT [12] concluded that the benefit of sodium bicarbonate was marginal relative to isotonic sodium chloride for preventing CI-AKI among critically ill patients. However, other studies indicated that the RenalGuard System [13–16] and hemodynamic guided hydration [17–19] were safe and effective in preventing CI-AKI. Because of these apparently discrepant results, we conducted a network meta-analysis (NMA) to assess the effects of various hydration strategies on the occurrence of CI-AKI in an effort to identify the optimal strategy for prevention of CI-AKI.


## 2. Methods

### 2.1. Data Search

This systematic review and meta-analysis were performed according to Cochrane Handbook guidelines [20]. The Web of Science, PubMed, OVID Medline, and Cochrane Library databases were searched using medical subject headings or keywords. Relevant published original studies that were published up to September 30, 2018, were examined. The search syntax was as follows: “contrast-induced acute kidney injury OR contrast-induced nephropathy OR CIN OR CI-AKI OR contrast acute renal failure OR contrast nephropathy” AND “hydration OR fluid administration OR volume expansion OR intravenous sodium bicarbonate OR saline infusion.”


### 2.2. Study Selection

An initial eligibility screen of all citations was conducted, and only studies that examined CI-AKI and hydration were selected for further full-text review. All included studies were RCTs; experimental studies were excluded. In addition, all included studies reported the prevention of CI-AKI after intravascular administration of CM; used clinical protocols that were hydration strategies, not pharmaceutical prevention strategies; had clear definitions of CI-AKI; and provided data on the outcome of interest (occurrence of CI-AKI within 2 days to 1 week after procedures).


### 2.3. Data Extraction and Quality Assessment

Two authors (C. Q. P. and J. R.) independently reviewed each article for eligibility. Any disagreement was resolved by discussion among the authors or involvement of a third author. Data extraction included the year of publication, sample size, patient characteristics, risk factors associated with CI-AKI (old age, diabetes mellitus, renal impairment, heart failure), and type and dosage of contrast medium. The primary endpoint was the occurrence of CI-AKI within 2 days to 1 week after intravascular administration of CM. Two investigators independently evaluated the quality of each study using the Jadad scale, which ranges from 0 (worst) to 5 (best) [21].


### 2.4. Statistical Analyses

The advantages of Bayesian NMA over traditional meta-analysis are its greater flexibility, its provision of more naturally interpretable results, and its ability to rank treatments by comparative effectiveness [22]. The occurrence of CI-AKI as a dichotomous outcome variable was expressed as an odds ratio (OR) and 95% confidence interval (CI). All P values were 2-sided, and a P value below 0.05 was considered significant. All analyses were conducted using the Bayesian Markov chain Monte Carlo method in WinBUGS V.1.4.3 (MRC Biostatistics Unit, Cambridge, United Kingdom) using the Microsoft Excel-based macro NetMetaXL V.1.6.1 (Canadian Agency for Drugs and Technologies in Health, Ottawa, Canada) [23]. A convergence test for each analysis was conducted by checking whether the Monte Carlo error was less than 5% of the SD of the effect estimates or the variance between the studies. Convergence was achieved for all analyses using 1000 “burn in” runs and 1000 model runs. NetMetaXL was also used to generate a forest plot, league table, and “rankogram” with surface under the cumulative ranking curve (SUCRA), which ranges from 0 (worst) to 100% (best). Inconsistency was assessed by comparing the residual deviance and deviance information criterion statistics in fitted consistency and inconsistency models.


## 2.1. Data Search

This systematic review and meta-analysis were performed according to Cochrane Handbook guidelines [20]. The Web of Science, PubMed, OVID Medline, and Cochrane Library databases were searched using medical subject headings or keywords. Relevant published original studies that were published up to September 30, 2018, were examined. The search syntax was as follows: “contrast-induced acute kidney injury OR contrast-induced nephropathy OR CIN OR CI-AKI OR contrast acute renal failure OR contrast nephropathy” AND “hydration OR fluid administration OR volume expansion OR intravenous sodium bicarbonate OR saline infusion.”


## 2.2. Study Selection

An initial eligibility screen of all citations was conducted, and only studies that examined CI-AKI and hydration were selected for further full-text review. All included studies were RCTs; experimental studies were excluded. In addition, all included studies reported the prevention of CI-AKI after intravascular administration of CM; used clinical protocols that were hydration strategies, not pharmaceutical prevention strategies; had clear definitions of CI-AKI; and provided data on the outcome of interest (occurrence of CI-AKI within 2 days to 1 week after procedures).


## 2.3. Data Extraction and Quality Assessment

Two authors (C. Q. P. and J. R.) independently reviewed each article for eligibility. Any disagreement was resolved by discussion among the authors or involvement of a third author. Data extraction included the year of publication, sample size, patient characteristics, risk factors associated with CI-AKI (old age, diabetes mellitus, renal impairment, heart failure), and type and dosage of contrast medium. The primary endpoint was the occurrence of CI-AKI within 2 days to 1 week after intravascular administration of CM. Two investigators independently evaluated the quality of each study using the Jadad scale, which ranges from 0 (worst) to 5 (best) [21].


## 2.4. Statistical Analyses

The advantages of Bayesian NMA over traditional meta-analysis are its greater flexibility, its provision of more naturally interpretable results, and its ability to rank treatments by comparative effectiveness [22]. The occurrence of CI-AKI as a dichotomous outcome variable was expressed as an odds ratio (OR) and 95% confidence interval (CI). All P values were 2-sided, and a P value below 0.05 was considered significant. All analyses were conducted using the Bayesian Markov chain Monte Carlo method in WinBUGS V.1.4.3 (MRC Biostatistics Unit, Cambridge, United Kingdom) using the Microsoft Excel-based macro NetMetaXL V.1.6.1 (Canadian Agency for Drugs and Technologies in Health, Ottawa, Canada) [23]. A convergence test for each analysis was conducted by checking whether the Monte Carlo error was less than 5% of the SD of the effect estimates or the variance between the studies. Convergence was achieved for all analyses using 1000 “burn in” runs and 1000 model runs. NetMetaXL was also used to generate a forest plot, league table, and “rankogram” with surface under the cumulative ranking curve (SUCRA), which ranges from 0 (worst) to 100% (best). Inconsistency was assessed by comparing the residual deviance and deviance information criterion statistics in fitted consistency and inconsistency models.


## 3. Results

### 3.1. Literature Search

We initially identified 3620 publications, assessed 703 RCTs for eligibility by review of the full texts, and ultimately included 60 RCTs which met the eligibility criteria (Figure1). These studies examined 21,293 patients (median: 222, interquartile range [IQR]: 120, 350) and 2232 CI-AKI events. All included RCTs were full-length journal articles. Agreement between the two reviewers at the full-text review stage was excellent (Cohen’s κ = 0.85).Figure 1
Identification and selection of studies for Bayesian network meta-analysis.


### 3.2. Characteristics of Studies and Participants

Table1 shows the characteristics of the included studies. The publication date ranged from 2002 to 2018, and about 50% of the studies were published after 2013. The proportion of male patients ranged from 25.0% to 98.1% (median [IQR]: 65.7 [56.9, 74.8]), and the mean age ranged from 56.2 to 82.9 years (67.8 [63.1, 72.5]). Thirty-one studies enrolled 12,519 patients who had high risk of CI-AKI. The baseline serum creatinine (SCr) level ranged from 61.4 to 236.4 μmol/L (117.1 [89.5, 136.9]), and the baseline estimated glomerular filtration rate (eGFR) ranged from 32 to 93.1 mL/min/1.73 m2 (49.2 [44.1, 74.2]). Twenty-three studies provided the values of left ventricular ejection fraction (LVEF); the mean LVEF ranged from 25% to 57.8% (49.0 [42.8, 54.5]). The percentage of diabetes mellitus (DM) patients ranged from 8% to 100%, and the percentage with heart failure (HF) ranged from 0.6% to 45.8%. A total of 8176 patients from 32 studies received intravenous low-osmolar nonionic CM, 9993 patients from 17 studies received iso-osmolar nonionic CM, and 317 patients from 2 studies received low-osmolar ionic CM. The mean Jadad score of the 60 RCTs was 3.2 (3 [2, 4]), indicating the overall study quality was good.Table 1
Characteristics of the included studies.
Studies
Patients (n)
Inclusion criteria/risk of CI-AKI
Mean age (years)
Males (%)
Baseline SCr (mg/dL)
Baseline eGFR (mL/min/1.73 m2)
Mean LVEF (%)
DM (%)
HF (%)
Treatment groups
Types of CM
CM dosage (mL)
Jadad score
No. of patients
Inclusion criteria/risk of CI-AKI
Mean age
Male (%)
Baseline SCr
Baseline eGFR
Mean LVEF
DM (%)
HF (%)
Groups
Types of CM
Dosage of CM
Jadad score
Weisbord et al. [11]
4993
High risk for renal complications and scheduled for angiography
69.8
93.6
132.6
50.2
80.9
7.4
SC vs. SB
Iodixanol or low-osmolar
85
5
4993
High risk for renal complications and scheduled for angiography
69.8
93.6
132.6
50.2
80.9
7.4
SC vs. SB
Iodixanol or low-osmolar
85
5
van Mourik et al. [24]
74
Symptomatic aortic valve stenosis and impaired renal function who underwent pre-TAVI CTA
82.9
44.6
104.3
47.4
31.1
SC vs. SB
Iopromide
90
3
74
Symptomatic aortic valve stenosis and impaired renal function who underwent pre-TAVI CTA
82.9
44.6
104.3
47.4
31.1
SC vs SB
Iopromide
90
3
Saratzis et al. [25]
58
Elective EVAR for infrarenal AAA
75
89.7
65.5
13.8
SC vs. SB
Iomeprol
126
3
58
Elective EVAR for infrarenal AAA
75
89.7
65.5
13.8
SC vs SB
Iomeprol
126
3
Maioli et al. [18]
296
Elective coronary angiographic procedures
71
68.2
89.3
48
24.7
SC vs. HDy
Iodixanol
131
3
296
Elective coronary angiographic procedures
71
68.2
89.3
48
24.7
SC vs HDy
Iodixanol
131
3
Kooiman et al. [26]
333
CKD patients undergoing elective cardiovascular diagnostic or interventional contrast procedures
73
64.6
50.5
38.7
16.5
SC vs. SB
Not mentioned
113
3
333
CKD patients undergoing elective cardiovascular diagnostic or interventional contrast procedures
73
64.6
50.5
38.7
16.5
SC vs SB
Not mentioned
113
3
Valette et al. [12]
307
Critically ill patients with stable renal function who received intravascular CM
56.2
67.8
61.4
13.4
6.5
SC vs. SB
Low-osmolar
90
4
307
Critically ill patients with stable renal function who received intravascular CM
56.2
67.8
61.4
13.4
6.5
SC vs SB
Low-osmolar
90
4
Nijssen et al. [10]
660
High-risk patients with eGFR of 30–59 ml/min/1.73 m2, undergoing an elective procedure requiring CM administration
72
61.7
118
47.4
32.6
Non vs. SC
Iopromide
90.5
3
660
High-risk patients with eGFR of 30–59 ml/min/1.73 m2, undergoing an elective procedure requiring CM administration
72
61.7
118
47.4
32.6
Non vs SC
Iopromide
90.5
3
Alonso et al. [27]
93
Patients receiving CM during CRT devices implantation
66.5
65.3
110.5
28.5
37
SC vs. SB
Iodixanol
102
2
93
Patients receiving CM during CRT devices implantation
66.5
65.3
110.5
28.5
37
SC vs SB
Iodixanol
102
2
Usmiani et al. [28]
124
Coronary angiography/PCI with eGFR of less than 60 ml/min/1.73 m2
75
74
130.8
44
25
84
SC vs. RenalGuard
Iodixanol
156
3
124
Coronary angiography/PCI with eGFR of less than 60 ml/min/1.73 m2
75
74
130.8
44
25
84
SC vs RenalGuard
Iodixanol
156
3
Turedi et al. [29]
172
Contrast-enhanced CTPA on suspicion of PE with at least one risk factor for CIN
75.5
51.7
85.4
SC vs. SB
Water-soluble, nonionic, low-osmolar
<100
3
172
Contrast-enhanced CTPA on suspicion of PE with at least one risk factor for CIN
75.5
51.7
85.4
SC vs SB
Water-soluble, nonionic, low-osmolar
<100
3
Qian et al. [19]
264
CKD and CHF undergoing coronary procedures
63.5
74.6
151
37.5
39.5
47.3
SC vs. HDy
Iodixanol
166
5
264
CKD and CHF undergoing coronary procedures
63.5
74.6
151
37.5
39.5
47.3
SC vs HDy
Iodixanol
166
5
Solomon et al. [30]
391
Elective coronary or peripheral angiography with eGFR <45 ml/min/1.73 m2
72
57.5
169.3
32.8
59.1
35.5
SC vs. SB
Not mentioned
107
4
391
Elective coronary or peripheral angiography with eGFR <45 ml/min/1.73 m2
72
57.5
169.3
32.8
59.1
35.5
SC vs SB
Not mentioned
107
4
Martin-Moreno et al. [31]
130
Receiving CM for CT scan
57.5
64.3
79.6
Non vs SB
Not mentioned
120
3
130
Receiving CM for CT scan
57.5
64.3
79.6
Non vs SB
Not mentioned
120
3
Jurado-Román et al. [32]
408
STEMI undergoing primary PCI
63.1
73.4
89
22.5
14.7
Non vs. SC
Iso-osmolar nonionic
174
2
408
STEMI undergoing primary PCI
63.1
73.4
89
22.5
14.7
Non vs SC
Iso-osmolar nonionic
174
2
Barbanti et al. [13]
112
TAVR
81
40.2
87.1
51.5
54.6
25
SC vs. RenalGuard
Buckinghamshire
175
3
112
TAVR
81
40.2
87.1
51.5
54.6
25
SC vs RenalGuard
Buckinghamshire
175
3
Yeganehkhah et al. [33]
100
CAG
59.7
53
99.5
43.8
39
SC vs. SB
Iohexol
45.4
3
100
CAG
59.7
53
99.5
43.8
39
SC vs SB
Iohexol
45.4
3
Yang et al. [34]
320
Elective cardiovascular procedures including CAG or interventional treatment
59.2
53.1
70.2
93.1
55.1
20
SC + NAC vs. SB + NAC
Iopromide
125
3
320
Elective cardiovascular procedures including CAG or interventional treatment
59.2
53.1
70.2
93.1
55.1
20
SC + NAC vs SB + NAC
Iopromide
125
3
Yang et al. [34]
320
Elective cardiovascular procedures including CAG or interventional treatment
59.2
53.1
70.2
93.1
55.1
20
SC vs. SB
Iopromide
125
3
320
Elective cardiovascular procedures including CAG or interventional treatment
59.2
53.1
70.2
93.1
55.1
20
SC vs SB
Iopromide
125
3
Thayssen et al. [35]
362
STEMI undergoing primary PCI within 12 hours from the onset of chest pain
62.5
78.5
77
90.5
50
9.7
SC vs. SB
Iodixanol
140
5
362
STEMI undergoing primary PCI within 12 hours from the onset of chest pain
62.5
78.5
77
90.5
50
9.7
SC vs SB
Iodixanol
140
5
Nieto-Rios et al. [36]
220
Tomography scan using CM or angiography
60
57.7
115.8
37.3
SC vs. SB
Iohexol
100
3
220
Tomography scan using CM or angiography
60
57.7
115.8
37.3
SC vs SB
Iohexol
100
3
Manari et al. [37]
592
STEMI within 12 h from symptom onset referred for primary angioplasty
65
74.8
88.5
81
48
16.6
11.8
SC vs. SB
Iodixanol
198
3
592
STEMI within 12 h from symptom onset referred for primary angioplasty
65
74.8
88.5
81
48
16.6
11.8
SC vs SB
Iodixanol
198
3
Mahmoodi et al. [38]
350
Coronary interventions
64.48
51.4
103
64.8
SC vs. SB
Iohexol
2
350
Coronary interventions
64.48
51.4
103
64.8
SC vs SB
Iohexol
2
Luo et al. [39]
216
STEMI
67
65.7
77
77.6
25
Non vs. SC
Iopamiron
234.9
3
216
STEMI
67
65.7
77
77.6
25
Non vs SC
Iopamiron
234.9
3
Kooiman et al. [40]
548
CKD patients receiving CE-CT
72.1
60.4
50.4
26.8
16.4
SC vs. SB
Iomeprol
105
5
548
CKD patients receiving CE-CT
72.1
60.4
50.4
26.8
16.4
SC vs SB
Iomeprol
105
5
Kooiman et al. [41]
138
CKD patients receiving CTPA
70.5
50
49.2
16.7
8
Non vs. SB
Iopromide or iobitridol or iodixanol
74
5
138
CKD patients receiving CTPA
70.5
50
49.2
16.7
8
Non vs SB
Iopromide, or iobitridol, or iodixanol
74
5
Brar et al. [17]
396
Referred to the cardiac catheterization laboratory with eGFR ≤ 60 mL/min/1.73 m2, and at least one of the following: DM, CHF, hypertension, or age older than 75 years
72
61.9
123.8
48
51.3
20.5
SC vs. HDy
Ioxilan
108
3
396
Referred to the cardiac catheterization laboratory with eGFR ≤ 60 mL/min/1.73 m2, and at least one of the following: DM, CHF, hypertension, or age older than 75 years
72
61.9
123.8
48
51.3
20.5
SC vs HDy
Ioxilan
108
3
Akyuz et al. [42]
225
At least one of the high-risk factors for developing CI-AKI and undergoing CAG and/or PCI
63.4
68.9
79.6
84.5
47.5
60.9
7.6
Oral vs. SC
Not mentioned
108
2
225
At least one of the high-risk factors for developing CI-AKI and undergoing CAG and/or PCI
63.4
68.9
79.6
84.5
47.5
60.9
7.6
Oral vs SC
Not mentioned
108
2
Kristeller et al. [43]
92
Stage 3 or higher CKD who underwent cardiac surgery using CPB
72.5
57.6
119.1
44.6
34.8
SC vs SB
Not mentioned
79
5
92
Stage 3 or higher CKD who underwent cardiac surgery using CPB
72.5
57.6
119.1
44.6
34.8
SC vs SB
Not mentioned
79
5
Koc et al. [44]
195
DM patients
62
52.3
88.4
100
SC vs. SB
Not mentioned
90
4
195
DM patients
62
52.3
88.4
100
SC vs SB
Not mentioned
90
4
Gu et al. [45]
859
Coronary angiography or angioplasty
59
72.2
90.1
74.2
20.6
0.6
SC vs. SC + diuresis
Not mentioned
100
2
859
Coronary angiography or angioplasty
59
72.2
90.1
74.2
20.6
0.6
SC vs SC + diuresis
Not mentioned
100
2
Boucek et al. [46]
120
Diabetic patients with impaired renal function, undergoing intra-arterial or intravenous use of CM
65
75
165
44.1
100
SC vs. SB
Low-osmolar nonionic iodinated
110
5
120
Diabetic patients with impaired renal function, undergoing intra-arterial or intravenous use of CM
65
75
165
44.1
100
SC vs SB
Low-osmolar nonionic iodinated
110
5
Marenzi et al. [47]
170
CKD undergoing coronary procedures
73
78.2
154.7
39
51.5
36.4
SC vs. RenalGuard
Iomeprol
170
3
170
CKD undergoing coronary procedures
73
78.2
154.7
39
51.5
36.4
SC vs RenalGuard
Iomeprol
170
3
Kong et al. [48]
80
Definitive or suspected coronary artery disease
56.5
53.8
105
23.8
Oral vs. SC
Iopromide
152
3
80
Definitive or suspected coronary artery disease
56.5
53.8
105
23.8
Oral vs SC
Iopromide
152
3
Klima et al. [49]
258
Renal insufficiency undergoing intravascular contrast procedures
77
64
137
43.6
37
44
SC vs. SB
Not mentioned
100
5
258
Renal insufficiency undergoing intravascular contrast procedures
77
64
137
43.6
37
44
SC vs SB
Not mentioned
100
5
Gomes et al. [50]
301
Patients at moderate to high risk for developing CIN who were referred for elective CAG or PCI
64
47.5
132.6
18.9
SC vs. SB
Not mentioned
125
2
301
Patients at moderate to high risk for developing CIN who were referred for elective CAG or PCI
64
47.5
132.6
18.9
SC vs SB
Not mentioned
125
2
Motohiro et al. [51]
155
eGFR <60 ml/min/1.73 m2 who were undergoing coronary angiography
72.5
69.7
136.6
44.3
55
60
SC vs. SB
Iopamidol
135
3
155
eGFR <60 ml/min/1.73 m2 who were undergoing coronary angiography
72.5
69.7
136.6
44.3
55
60
SC vs SB
Iopamidol
135
3
Maioli et al. [52]
300
STEMI undergoing primary PCI
65
25
95.9
42.5
21.7
24
Non vs. SB
Iodixanol
216
3
300
STEMI undergoing primary PCI
65
25
95.9
42.5
21.7
24
Non vs SB
Iodixanol
216
3
Lee et al. [53]
382
Diabetic patients with renal disease (serum creatinine >1.1 mg/dl and eGFR <60 ml/min/1.73 m2)
68
70.9
132.6
46
100
SC vs. SB
Iodixanol
116.5
3
382
Diabetic patients with renal disease (serum creatinine >1.1 mg/dl and eGFR <60 ml/min/1.73 m2)
68
70.9
132.6
46
100
SC vs SB
Iodixanol
116.5
3
Hafiz et al. [54]
320
Patients with baseline renal insufficiency scheduled to undergo catheterization
73
56.9
141.4
47.2
SC vs. SB
Nonionic, low-osmolar
115
3
320
Patients with baseline renal insufficiency scheduled to undergo catheterization
73
56.9
141.4
47.2
SC vs SB
Nonionic, low-osmolar
115
3
Briguori et al. [55]
292
High-risk patients with an eGFR ≤30 ml/min/1.73 m2 and/or a risk score ≥11
76
65.4
158.7
32
47
70.2
28.4
SB vs. RenalGuard
Iodixanol
140
3
292
High-risk patients with an eGFR ≤30 ml/min/1.73 m2 and/or a risk score ≥11
76
65.4
158.7
32
47
70.2
28.4
SB vs RenalGuard
Iodixanol
140
3
Wróbel et al. [56]
102
Coronary angiography and/or angioplasty, and had comorbidities that increase the risk of CIN
65.5
56.9
236.4
Oral vs. SC
Loversol
69.5
2
102
Coronary angiography and/or angioplasty, and had comorbidities that increase the risk of CIN
65.5
56.9
236.4
Oral vs SC
Loversol
69.5
2
Vasheghani-Farahani et al. [57]
72
CAG, with SCr 1.5 mg/dL within 2 weeks, having at least 1 of the risk factors
62
79.2
151.2
44.2
36.1
34.7
45.8
0.45 SC vs. SB
Iohexol
117.5
3
72
CAG, with SCr 1.5 mg/dL within 2 weeks, having at least 1 of the risk factors
62
79.2
151.2
44.2
36.1
34.7
45.8
0.45 SC vs SB
Iohexol
117.5
3
Cho et al. [58]
91
Undergoing an elective CAG
78
50.5
123
38.5
17.6
SC vs. SB
Isoversol
128
2
91
Undergoing an elective CAG
78
50.5
123
38.5
17.6
SC vs SB
Isoversol
128
2
Vasheghani-Farahani et al. [59]
265
Serum creatinine level of 1.5 mg/dL or greater undergoing elective CAG
63.3
83
145.4
45.9
51.7
21.5
SC vs. SB
Iohexol
114
5
265
Serum creatinine level of 1.5 mg/dL or greater undergoing elective CAG
63.3
83
145.4
45.9
51.7
21.5
SC vs SB
Iohexol
114
5
Tamura et al. [60]
144
Scheduled for elective CAG or PCI
72.8
87.5
121.1
39.1
57.8
58.3
SC vs. SB
Iohexol
85
3
144
Scheduled for elective CAG or PCI
72.8
87.5
121.1
39.1
57.8
58.3
SC vs SB
Iohexol
85
3
Pakfetrat et al. [61]
192
Undergoing elective CAG or PCI
57.9
61.5
97.2
72.2
50.5
29.7
5.2
SC vs. SB
Iodixanol
65
4
192
Undergoing elective CAG or PCI
57.9
61.5
97.2
72.2
50.5
29.7
5.2
SC vs SB
Iodixanol
65
4
Haase et al. [62]
100
At increased risk of postoperative acute renal dysfunction who were scheduled for elective or urgent cardiac surgery necessitating the use of CPB
71
66
90.7
SC vs. SB
Not mentioned
5
100
At increased risk of postoperative acute renal dysfunction who were scheduled for elective or urgent cardiac surgery necessitating the use of CPB
71
66
90.7
SC vs SB
Not mentioned
5
Budhiraja et al. [63]
187
Nonemergent CAG, baseline serum creatinine >1.0 mg/dL, and availability of serum creatinine values at days 1–3
68
125.8
57.2
30.5
SC vs. SB
Iopromide
199
2
187
Nonemergent CAG, baseline serum creatinine >1.0 mg/dL, and availability of serum creatinine values at days 1–3
68
125.8
57.2
30.5
SC vs SB
Iopromide
199
2
Angoulvant et al. [64]
201
Scheduled for elective CAG, with or without PTCA with a baseline SCr < 140μmol/L
62
80.6
86.2
Oral vs. SC
Not mentioned
290
3
201
Scheduled for elective CAG, with or without PTCA with a baseline SCr< 140μmol/L
62
80.6
86.2
Oral vs SC
Not mentioned
290
3
Maioli et al. [65]
502
Undergoing coronary angiographic procedures with estimated creatinine clearance <60 ml/min
74
59
107
46.5
59.1
SC vs. SB
Iodixanol
165
3
502
Undergoing coronary angiographic procedures with estimated creatinine clearance <60 ml/min
74
59
107
46.5
59.1
SC vs SB
Iodixanol
165
3
Chen et al. [66]
660
Myocardial ischemia (angina or positive exercise treadmill) scheduled for PCI, with SCr<1.5 mg/dl
60
85
114.9
54
8
Non vs. SC
Iso-osmolar nonionic
285
2
660
Myocardial ischemia (angina or positive exercise treadmill) scheduled for PCI, with SCr < 1.5 mg/dl
60
85
114.9
54
8
Non vs SC
Iso-osmolar nonionic
285
2
Chen et al. [66]
276
Myocardial ischemia (angina or positive exercise treadmill) scheduled for PCI, with SCr ≥ 1.5 mg/dl
63
82
221
41
22
Non vs. SC
Iso-osmolar nonionic
298
2
276
Myocardial ischemia (angina or positive exercise treadmill) scheduled for PCI, with SCr ≥ 1.5 mg/dl
63
82
221
41
22
Non vs SC
Iso-osmolar nonionic
298
2
Brar et al. [67]
353
Patients with stable renal disease and undergoing CAG
71
63.9
131.7
48
57
44.5
27.2
SC vs. SB
Ioxilan
132
5
353
Patients with stable renal disease and undergoing CAG
71
63.9
131.7
48
57
44.5
27.2
SC vs SB
Ioxilan
132
5
Adolph et al. [68]
145
Stable renal insufficiency and undergoing elective diagnostic or interventional coronary angiography
72.6
77.9
132.6
33.8
SC vs. SB
Iodixanol
140
5
145
Stable renal insufficiency and undergoing elective diagnostic or interventional coronary angiography
72.6
77.9
132.6
33.8
SC vs SB
Iodixanol
140
5
Schmidt et al. [69]
96
CAG
67.6
74
146.7
64.6
SC vs. SB
Optiray
186
2
96
CAG
67.6
74
146.7
64.6
SC vs SB
Optiray
186
2
Ozcan et al. [70]
264
Scheduled for CAG or PCI and had a baseline creatinine level >1.2 mg/dL
69
74.6
122.9
45.1
26.5
SC vs. SB
Ioxaglate
110
2
264
Scheduled for CAG or PCI and had a baseline creatinine level >1.2 mg/dL
69
74.6
122.9
45.1
26.5
SC vs SB
Ioxaglate
110
2
Masuda et al. [71]
59
Scheduled to undergo an emergency coronary angiography or intervention
75
44.1
116.2
30.5
SC vs. SB
Iopamidol
116
3
59
Scheduled to undergo an emergency coronary angiography or intervention
75
44.1
116.2
30.5
SC vs SB
Iopamidol
116
3
Dussol et al. [72]
156
CKD, who were undergoing radiological procedures with CM
65
67.9
204.5
33.1
28.8
16
SC vs. SC + diuresis
Nonionic, low osmolar
117
5
156
CKD, who were undergoing radiological procedures with CM
65
67.9
204.5
33.1
28.8
16
SC vs SC + diuresis
Nonionic, low osmolar
117
5
Mueller et al. [73]
425
Scheduled for elective or emergency PCI
64
75
89
16
0.45 SC vs. SC
Iopromide
226
2
425
Scheduled for elective or emergency PCI
64
75
89
16
0.45 SC vs SC
Iopromide
226
2
Merten et al. [74]
119
Stable renal insufficiency undergoing diagnostic or interventional procedures requiring radiographic contrast, SCr> 1.1 mg/dL
68
74.8
159.1
47.9
SC vs. SB
Iopamidol
132
3
119
Stable renal insufficiency undergoing diagnostic or interventional procedures requiring radiographic contrast, SCr> 1.1 mg/dL
68
74.8
159.1
47.9
SC vs SB
Iopamidol
132
3
Trivedi et al. [75]
53
Scheduled to undergo nonemergency CAG
67.9
98.1
106.4
52.1
18.9
Oral vs. SC
Ionic, low-osmolar
148
2
53
Scheduled to undergo nonemergency CAG
67.9
98.1
106.4
52.1
18.9
Oral vs SC
Ionic, low-osmolar
148
2
Mueller et al. [76]
1383
Scheduled for elective or emergency CAG
64
74.4
81.77
15.7
0.45 SC vs. SC
Ultravist or imeron
234
2
1383
Scheduled for elective or emergency CAG
64
74.4
81.77
15.7
0.45 SC vs SC
Ultravist, or imeron
234
2
CI-AKI: contrast-induced acute kidney injury; SCr: serum creatinine; eGFR: estimated glomerular filtration rate; LVEF: left ventricular ejection fraction; DM: diabetes mellitus; HF: heart failure; CM: contrast media; CTA: computed tomography angiography; TAVI: transcatheter aortic valve implantation; EVAR: elective endovascular aneurysm repair; AAA: abdominal aortic aneurysm; CKD: chronic kidney disease; CRT: cardiac resynchronization therapy; CTPA: computed tomography pulmonary angiography; PE: pulmonary embolism; CIN: contrast-induced nephropathy; CHF: chronic heart failure; CT: computed tomography; TAVR: transcatheter aortic valve replacement; CAG: coronary angiography; CE-CT: contrast media-enhanced computed tomography; CPB: cardiopulmonary bypass; PTCA: percutaneous transluminal coronary angioplasty; NAC: N-acetylcysteine. Treatment groups: SC: intravenous 0.9% sodium chloride; SB: intravenous sodium bicarbonate; Non: nonhydration; Oral: oral hydration; RenalGuard: RenalGuard system; HDy: hemodynamic guided hydration; SC + diuresis: intravenous 0.9% sodium chloride + diuresis; 0.45 SC: 0.45% sodium chloride.


### 3.3. Network Meta-Analysis

Figure2 shows all the comparisons in the NMA. Thirty-seven studies (13,365 participants) compared the efficacy of intravenous sodium bicarbonate and 0.9% sodium chloride. The other hydration strategies were nonhydration (8 studies, 1396 patients), oral hydration (6 studies, 355 patients), intravenous half iso-osmolar saline (3 studies, 968 patients), intravenous hydration, mainly normal saline + diuresis (2 studies [26, 31], 501 patients), hemodynamic guided hydration (3 studies, 458 patients), and RenalGuard system guided hydration (4 studies, 348 patients).Figure 2
Network diagram of eight hydration strategies used to prevent contrast-induced acute kidney injury in the 60 included studies. Circles represent hydration strategies and lines represent direct comparisons. Circle size indicates the number of participants who received each treatment, and line thickness indicates the number of studies in each comparison.We compared the ORs of the different hydration strategies using a forest plot (Figure3) and analyzed the results of the random effects consistency NMA using a league table, which shows all pairwise comparisons (Figure 4). Taken together, these results indicate that, relative to typical intravenous 0.9% sodium chloride hydration (reference), the occurrence of CI-AKI was significantly reduced by intravenous sodium bicarbonate (OR [95% CI]: 0.74 [0.57, 0.93]), hemodynamic guided hydration (0.41 [0.18, 0.93]), and RenalGuard system guided hydration (0.32 [0.14, 0.70]). Oral hydration (0.72 [0.28, 1.82]) and intravenous 0.9% sodium chloride (0.64 [0.39, 1.08]) were each noninferior to no hydration for prevention of CI-AKI. Relative to oral hydration (reference), intravenous 0.9% sodium chloride or sodium bicarbonate and hemodynamic guided hydration were each noninferior in prevention of CI-AKI, but RenalGuard guided hydration was superior (0.21 [0.07, 0.63]). Intravenous hydration plus diuresis also did not decrease the risk of CI-AKI relative to oral hydration and no hydration.Figure 3
Forest plot showing the effect of different hydration strategies. Summary estimates from the pooled studies with 95% confidence intervals are indicated for fixed effects (open diamonds) and random effects (filled diamonds) models.Figure 4
League table, showing all pairwise comparisons of studies.A rankogram and SUCRA values indicated the RenalGuard system was best (SUCRA = 0.974) followed by hemodynamic guided hydration (SUCRAs = 0.849; Figure5). Intravenous sodium bicarbonate had a SUCRA of 0.667. The SUCRAs for intravenous 0.9% sodium chloride, intravenous hydration plus diuresis, oral and no hydration, and the other treatments ranged from 0.197 to 0.441, and their rankings were similar. Hydration using half iso-osmolar saline alone was the least effective treatment.Figure 5
Rankogram of the effect of different hydration strategies in reducing the risk of contrast-induced acute kidney injury.


### 3.4. Inconsistency Analysis

We performed network inconsistency assessment for the fixed effect model for the 60 studies (Figure6). The resulting plot demonstrated that nearly all the studies were near the line of equality and that the results were therefore consistent. However, there was some evidence of inconsistency in 3 noninferiority studies [10, 31]. In particular, Martin-Moreno et al. [31] and Nijssen et al. [10] found that intravenous sodium bicarbonate and 0.9% sodium chloride were noninferior to oral hydration.Figure 6
Inconsistency plot of enrolled studies, showing the posterior mean deviance of each study from the consistency model (horizontal axis) and the inconsistency model (vertical axis).


## 3.1. Literature Search

We initially identified 3620 publications, assessed 703 RCTs for eligibility by review of the full texts, and ultimately included 60 RCTs which met the eligibility criteria (Figure1). These studies examined 21,293 patients (median: 222, interquartile range [IQR]: 120, 350) and 2232 CI-AKI events. All included RCTs were full-length journal articles. Agreement between the two reviewers at the full-text review stage was excellent (Cohen’s κ = 0.85).Figure 1
Identification and selection of studies for Bayesian network meta-analysis.


## 3.2. Characteristics of Studies and Participants

Table1 shows the characteristics of the included studies. The publication date ranged from 2002 to 2018, and about 50% of the studies were published after 2013. The proportion of male patients ranged from 25.0% to 98.1% (median [IQR]: 65.7 [56.9, 74.8]), and the mean age ranged from 56.2 to 82.9 years (67.8 [63.1, 72.5]). Thirty-one studies enrolled 12,519 patients who had high risk of CI-AKI. The baseline serum creatinine (SCr) level ranged from 61.4 to 236.4 μmol/L (117.1 [89.5, 136.9]), and the baseline estimated glomerular filtration rate (eGFR) ranged from 32 to 93.1 mL/min/1.73 m2 (49.2 [44.1, 74.2]). Twenty-three studies provided the values of left ventricular ejection fraction (LVEF); the mean LVEF ranged from 25% to 57.8% (49.0 [42.8, 54.5]). The percentage of diabetes mellitus (DM) patients ranged from 8% to 100%, and the percentage with heart failure (HF) ranged from 0.6% to 45.8%. A total of 8176 patients from 32 studies received intravenous low-osmolar nonionic CM, 9993 patients from 17 studies received iso-osmolar nonionic CM, and 317 patients from 2 studies received low-osmolar ionic CM. The mean Jadad score of the 60 RCTs was 3.2 (3 [2, 4]), indicating the overall study quality was good.Table 1
Characteristics of the included studies.
Studies
Patients (n)
Inclusion criteria/risk of CI-AKI
Mean age (years)
Males (%)
Baseline SCr (mg/dL)
Baseline eGFR (mL/min/1.73 m2)
Mean LVEF (%)
DM (%)
HF (%)
Treatment groups
Types of CM
CM dosage (mL)
Jadad score
No. of patients
Inclusion criteria/risk of CI-AKI
Mean age
Male (%)
Baseline SCr
Baseline eGFR
Mean LVEF
DM (%)
HF (%)
Groups
Types of CM
Dosage of CM
Jadad score
Weisbord et al. [11]
4993
High risk for renal complications and scheduled for angiography
69.8
93.6
132.6
50.2
80.9
7.4
SC vs. SB
Iodixanol or low-osmolar
85
5
4993
High risk for renal complications and scheduled for angiography
69.8
93.6
132.6
50.2
80.9
7.4
SC vs. SB
Iodixanol or low-osmolar
85
5
van Mourik et al. [24]
74
Symptomatic aortic valve stenosis and impaired renal function who underwent pre-TAVI CTA
82.9
44.6
104.3
47.4
31.1
SC vs. SB
Iopromide
90
3
74
Symptomatic aortic valve stenosis and impaired renal function who underwent pre-TAVI CTA
82.9
44.6
104.3
47.4
31.1
SC vs SB
Iopromide
90
3
Saratzis et al. [25]
58
Elective EVAR for infrarenal AAA
75
89.7
65.5
13.8
SC vs. SB
Iomeprol
126
3
58
Elective EVAR for infrarenal AAA
75
89.7
65.5
13.8
SC vs SB
Iomeprol
126
3
Maioli et al. [18]
296
Elective coronary angiographic procedures
71
68.2
89.3
48
24.7
SC vs. HDy
Iodixanol
131
3
296
Elective coronary angiographic procedures
71
68.2
89.3
48
24.7
SC vs HDy
Iodixanol
131
3
Kooiman et al. [26]
333
CKD patients undergoing elective cardiovascular diagnostic or interventional contrast procedures
73
64.6
50.5
38.7
16.5
SC vs. SB
Not mentioned
113
3
333
CKD patients undergoing elective cardiovascular diagnostic or interventional contrast procedures
73
64.6
50.5
38.7
16.5
SC vs SB
Not mentioned
113
3
Valette et al. [12]
307
Critically ill patients with stable renal function who received intravascular CM
56.2
67.8
61.4
13.4
6.5
SC vs. SB
Low-osmolar
90
4
307
Critically ill patients with stable renal function who received intravascular CM
56.2
67.8
61.4
13.4
6.5
SC vs SB
Low-osmolar
90
4
Nijssen et al. [10]
660
High-risk patients with eGFR of 30–59 ml/min/1.73 m2, undergoing an elective procedure requiring CM administration
72
61.7
118
47.4
32.6
Non vs. SC
Iopromide
90.5
3
660
High-risk patients with eGFR of 30–59 ml/min/1.73 m2, undergoing an elective procedure requiring CM administration
72
61.7
118
47.4
32.6
Non vs SC
Iopromide
90.5
3
Alonso et al. [27]
93
Patients receiving CM during CRT devices implantation
66.5
65.3
110.5
28.5
37
SC vs. SB
Iodixanol
102
2
93
Patients receiving CM during CRT devices implantation
66.5
65.3
110.5
28.5
37
SC vs SB
Iodixanol
102
2
Usmiani et al. [28]
124
Coronary angiography/PCI with eGFR of less than 60 ml/min/1.73 m2
75
74
130.8
44
25
84
SC vs. RenalGuard
Iodixanol
156
3
124
Coronary angiography/PCI with eGFR of less than 60 ml/min/1.73 m2
75
74
130.8
44
25
84
SC vs RenalGuard
Iodixanol
156
3
Turedi et al. [29]
172
Contrast-enhanced CTPA on suspicion of PE with at least one risk factor for CIN
75.5
51.7
85.4
SC vs. SB
Water-soluble, nonionic, low-osmolar
<100
3
172
Contrast-enhanced CTPA on suspicion of PE with at least one risk factor for CIN
75.5
51.7
85.4
SC vs SB
Water-soluble, nonionic, low-osmolar
<100
3
Qian et al. [19]
264
CKD and CHF undergoing coronary procedures
63.5
74.6
151
37.5
39.5
47.3
SC vs. HDy
Iodixanol
166
5
264
CKD and CHF undergoing coronary procedures
63.5
74.6
151
37.5
39.5
47.3
SC vs HDy
Iodixanol
166
5
Solomon et al. [30]
391
Elective coronary or peripheral angiography with eGFR <45 ml/min/1.73 m2
72
57.5
169.3
32.8
59.1
35.5
SC vs. SB
Not mentioned
107
4
391
Elective coronary or peripheral angiography with eGFR <45 ml/min/1.73 m2
72
57.5
169.3
32.8
59.1
35.5
SC vs SB
Not mentioned
107
4
Martin-Moreno et al. [31]
130
Receiving CM for CT scan
57.5
64.3
79.6
Non vs SB
Not mentioned
120
3
130
Receiving CM for CT scan
57.5
64.3
79.6
Non vs SB
Not mentioned
120
3
Jurado-Román et al. [32]
408
STEMI undergoing primary PCI
63.1
73.4
89
22.5
14.7
Non vs. SC
Iso-osmolar nonionic
174
2
408
STEMI undergoing primary PCI
63.1
73.4
89
22.5
14.7
Non vs SC
Iso-osmolar nonionic
174
2
Barbanti et al. [13]
112
TAVR
81
40.2
87.1
51.5
54.6
25
SC vs. RenalGuard
Buckinghamshire
175
3
112
TAVR
81
40.2
87.1
51.5
54.6
25
SC vs RenalGuard
Buckinghamshire
175
3
Yeganehkhah et al. [33]
100
CAG
59.7
53
99.5
43.8
39
SC vs. SB
Iohexol
45.4
3
100
CAG
59.7
53
99.5
43.8
39
SC vs SB
Iohexol
45.4
3
Yang et al. [34]
320
Elective cardiovascular procedures including CAG or interventional treatment
59.2
53.1
70.2
93.1
55.1
20
SC + NAC vs. SB + NAC
Iopromide
125
3
320
Elective cardiovascular procedures including CAG or interventional treatment
59.2
53.1
70.2
93.1
55.1
20
SC + NAC vs SB + NAC
Iopromide
125
3
Yang et al. [34]
320
Elective cardiovascular procedures including CAG or interventional treatment
59.2
53.1
70.2
93.1
55.1
20
SC vs. SB
Iopromide
125
3
320
Elective cardiovascular procedures including CAG or interventional treatment
59.2
53.1
70.2
93.1
55.1
20
SC vs SB
Iopromide
125
3
Thayssen et al. [35]
362
STEMI undergoing primary PCI within 12 hours from the onset of chest pain
62.5
78.5
77
90.5
50
9.7
SC vs. SB
Iodixanol
140
5
362
STEMI undergoing primary PCI within 12 hours from the onset of chest pain
62.5
78.5
77
90.5
50
9.7
SC vs SB
Iodixanol
140
5
Nieto-Rios et al. [36]
220
Tomography scan using CM or angiography
60
57.7
115.8
37.3
SC vs. SB
Iohexol
100
3
220
Tomography scan using CM or angiography
60
57.7
115.8
37.3
SC vs SB
Iohexol
100
3
Manari et al. [37]
592
STEMI within 12 h from symptom onset referred for primary angioplasty
65
74.8
88.5
81
48
16.6
11.8
SC vs. SB
Iodixanol
198
3
592
STEMI within 12 h from symptom onset referred for primary angioplasty
65
74.8
88.5
81
48
16.6
11.8
SC vs SB
Iodixanol
198
3
Mahmoodi et al. [38]
350
Coronary interventions
64.48
51.4
103
64.8
SC vs. SB
Iohexol
2
350
Coronary interventions
64.48
51.4
103
64.8
SC vs SB
Iohexol
2
Luo et al. [39]
216
STEMI
67
65.7
77
77.6
25
Non vs. SC
Iopamiron
234.9
3
216
STEMI
67
65.7
77
77.6
25
Non vs SC
Iopamiron
234.9
3
Kooiman et al. [40]
548
CKD patients receiving CE-CT
72.1
60.4
50.4
26.8
16.4
SC vs. SB
Iomeprol
105
5
548
CKD patients receiving CE-CT
72.1
60.4
50.4
26.8
16.4
SC vs SB
Iomeprol
105
5
Kooiman et al. [41]
138
CKD patients receiving CTPA
70.5
50
49.2
16.7
8
Non vs. SB
Iopromide or iobitridol or iodixanol
74
5
138
CKD patients receiving CTPA
70.5
50
49.2
16.7
8
Non vs SB
Iopromide, or iobitridol, or iodixanol
74
5
Brar et al. [17]
396
Referred to the cardiac catheterization laboratory with eGFR ≤ 60 mL/min/1.73 m2, and at least one of the following: DM, CHF, hypertension, or age older than 75 years
72
61.9
123.8
48
51.3
20.5
SC vs. HDy
Ioxilan
108
3
396
Referred to the cardiac catheterization laboratory with eGFR ≤ 60 mL/min/1.73 m2, and at least one of the following: DM, CHF, hypertension, or age older than 75 years
72
61.9
123.8
48
51.3
20.5
SC vs HDy
Ioxilan
108
3
Akyuz et al. [42]
225
At least one of the high-risk factors for developing CI-AKI and undergoing CAG and/or PCI
63.4
68.9
79.6
84.5
47.5
60.9
7.6
Oral vs. SC
Not mentioned
108
2
225
At least one of the high-risk factors for developing CI-AKI and undergoing CAG and/or PCI
63.4
68.9
79.6
84.5
47.5
60.9
7.6
Oral vs SC
Not mentioned
108
2
Kristeller et al. [43]
92
Stage 3 or higher CKD who underwent cardiac surgery using CPB
72.5
57.6
119.1
44.6
34.8
SC vs SB
Not mentioned
79
5
92
Stage 3 or higher CKD who underwent cardiac surgery using CPB
72.5
57.6
119.1
44.6
34.8
SC vs SB
Not mentioned
79
5
Koc et al. [44]
195
DM patients
62
52.3
88.4
100
SC vs. SB
Not mentioned
90
4
195
DM patients
62
52.3
88.4
100
SC vs SB
Not mentioned
90
4
Gu et al. [45]
859
Coronary angiography or angioplasty
59
72.2
90.1
74.2
20.6
0.6
SC vs. SC + diuresis
Not mentioned
100
2
859
Coronary angiography or angioplasty
59
72.2
90.1
74.2
20.6
0.6
SC vs SC + diuresis
Not mentioned
100
2
Boucek et al. [46]
120
Diabetic patients with impaired renal function, undergoing intra-arterial or intravenous use of CM
65
75
165
44.1
100
SC vs. SB
Low-osmolar nonionic iodinated
110
5
120
Diabetic patients with impaired renal function, undergoing intra-arterial or intravenous use of CM
65
75
165
44.1
100
SC vs SB
Low-osmolar nonionic iodinated
110
5
Marenzi et al. [47]
170
CKD undergoing coronary procedures
73
78.2
154.7
39
51.5
36.4
SC vs. RenalGuard
Iomeprol
170
3
170
CKD undergoing coronary procedures
73
78.2
154.7
39
51.5
36.4
SC vs RenalGuard
Iomeprol
170
3
Kong et al. [48]
80
Definitive or suspected coronary artery disease
56.5
53.8
105
23.8
Oral vs. SC
Iopromide
152
3
80
Definitive or suspected coronary artery disease
56.5
53.8
105
23.8
Oral vs SC
Iopromide
152
3
Klima et al. [49]
258
Renal insufficiency undergoing intravascular contrast procedures
77
64
137
43.6
37
44
SC vs. SB
Not mentioned
100
5
258
Renal insufficiency undergoing intravascular contrast procedures
77
64
137
43.6
37
44
SC vs SB
Not mentioned
100
5
Gomes et al. [50]
301
Patients at moderate to high risk for developing CIN who were referred for elective CAG or PCI
64
47.5
132.6
18.9
SC vs. SB
Not mentioned
125
2
301
Patients at moderate to high risk for developing CIN who were referred for elective CAG or PCI
64
47.5
132.6
18.9
SC vs SB
Not mentioned
125
2
Motohiro et al. [51]
155
eGFR <60 ml/min/1.73 m2 who were undergoing coronary angiography
72.5
69.7
136.6
44.3
55
60
SC vs. SB
Iopamidol
135
3
155
eGFR <60 ml/min/1.73 m2 who were undergoing coronary angiography
72.5
69.7
136.6
44.3
55
60
SC vs SB
Iopamidol
135
3
Maioli et al. [52]
300
STEMI undergoing primary PCI
65
25
95.9
42.5
21.7
24
Non vs. SB
Iodixanol
216
3
300
STEMI undergoing primary PCI
65
25
95.9
42.5
21.7
24
Non vs SB
Iodixanol
216
3
Lee et al. [53]
382
Diabetic patients with renal disease (serum creatinine >1.1 mg/dl and eGFR <60 ml/min/1.73 m2)
68
70.9
132.6
46
100
SC vs. SB
Iodixanol
116.5
3
382
Diabetic patients with renal disease (serum creatinine >1.1 mg/dl and eGFR <60 ml/min/1.73 m2)
68
70.9
132.6
46
100
SC vs SB
Iodixanol
116.5
3
Hafiz et al. [54]
320
Patients with baseline renal insufficiency scheduled to undergo catheterization
73
56.9
141.4
47.2
SC vs. SB
Nonionic, low-osmolar
115
3
320
Patients with baseline renal insufficiency scheduled to undergo catheterization
73
56.9
141.4
47.2
SC vs SB
Nonionic, low-osmolar
115
3
Briguori et al. [55]
292
High-risk patients with an eGFR ≤30 ml/min/1.73 m2 and/or a risk score ≥11
76
65.4
158.7
32
47
70.2
28.4
SB vs. RenalGuard
Iodixanol
140
3
292
High-risk patients with an eGFR ≤30 ml/min/1.73 m2 and/or a risk score ≥11
76
65.4
158.7
32
47
70.2
28.4
SB vs RenalGuard
Iodixanol
140
3
Wróbel et al. [56]
102
Coronary angiography and/or angioplasty, and had comorbidities that increase the risk of CIN
65.5
56.9
236.4
Oral vs. SC
Loversol
69.5
2
102
Coronary angiography and/or angioplasty, and had comorbidities that increase the risk of CIN
65.5
56.9
236.4
Oral vs SC
Loversol
69.5
2
Vasheghani-Farahani et al. [57]
72
CAG, with SCr 1.5 mg/dL within 2 weeks, having at least 1 of the risk factors
62
79.2
151.2
44.2
36.1
34.7
45.8
0.45 SC vs. SB
Iohexol
117.5
3
72
CAG, with SCr 1.5 mg/dL within 2 weeks, having at least 1 of the risk factors
62
79.2
151.2
44.2
36.1
34.7
45.8
0.45 SC vs SB
Iohexol
117.5
3
Cho et al. [58]
91
Undergoing an elective CAG
78
50.5
123
38.5
17.6
SC vs. SB
Isoversol
128
2
91
Undergoing an elective CAG
78
50.5
123
38.5
17.6
SC vs SB
Isoversol
128
2
Vasheghani-Farahani et al. [59]
265
Serum creatinine level of 1.5 mg/dL or greater undergoing elective CAG
63.3
83
145.4
45.9
51.7
21.5
SC vs. SB
Iohexol
114
5
265
Serum creatinine level of 1.5 mg/dL or greater undergoing elective CAG
63.3
83
145.4
45.9
51.7
21.5
SC vs SB
Iohexol
114
5
Tamura et al. [60]
144
Scheduled for elective CAG or PCI
72.8
87.5
121.1
39.1
57.8
58.3
SC vs. SB
Iohexol
85
3
144
Scheduled for elective CAG or PCI
72.8
87.5
121.1
39.1
57.8
58.3
SC vs SB
Iohexol
85
3
Pakfetrat et al. [61]
192
Undergoing elective CAG or PCI
57.9
61.5
97.2
72.2
50.5
29.7
5.2
SC vs. SB
Iodixanol
65
4
192
Undergoing elective CAG or PCI
57.9
61.5
97.2
72.2
50.5
29.7
5.2
SC vs SB
Iodixanol
65
4
Haase et al. [62]
100
At increased risk of postoperative acute renal dysfunction who were scheduled for elective or urgent cardiac surgery necessitating the use of CPB
71
66
90.7
SC vs. SB
Not mentioned
5
100
At increased risk of postoperative acute renal dysfunction who were scheduled for elective or urgent cardiac surgery necessitating the use of CPB
71
66
90.7
SC vs SB
Not mentioned
5
Budhiraja et al. [63]
187
Nonemergent CAG, baseline serum creatinine >1.0 mg/dL, and availability of serum creatinine values at days 1–3
68
125.8
57.2
30.5
SC vs. SB
Iopromide
199
2
187
Nonemergent CAG, baseline serum creatinine >1.0 mg/dL, and availability of serum creatinine values at days 1–3
68
125.8
57.2
30.5
SC vs SB
Iopromide
199
2
Angoulvant et al. [64]
201
Scheduled for elective CAG, with or without PTCA with a baseline SCr < 140μmol/L
62
80.6
86.2
Oral vs. SC
Not mentioned
290
3
201
Scheduled for elective CAG, with or without PTCA with a baseline SCr< 140μmol/L
62
80.6
86.2
Oral vs SC
Not mentioned
290
3
Maioli et al. [65]
502
Undergoing coronary angiographic procedures with estimated creatinine clearance <60 ml/min
74
59
107
46.5
59.1
SC vs. SB
Iodixanol
165
3
502
Undergoing coronary angiographic procedures with estimated creatinine clearance <60 ml/min
74
59
107
46.5
59.1
SC vs SB
Iodixanol
165
3
Chen et al. [66]
660
Myocardial ischemia (angina or positive exercise treadmill) scheduled for PCI, with SCr<1.5 mg/dl
60
85
114.9
54
8
Non vs. SC
Iso-osmolar nonionic
285
2
660
Myocardial ischemia (angina or positive exercise treadmill) scheduled for PCI, with SCr < 1.5 mg/dl
60
85
114.9
54
8
Non vs SC
Iso-osmolar nonionic
285
2
Chen et al. [66]
276
Myocardial ischemia (angina or positive exercise treadmill) scheduled for PCI, with SCr ≥ 1.5 mg/dl
63
82
221
41
22
Non vs. SC
Iso-osmolar nonionic
298
2
276
Myocardial ischemia (angina or positive exercise treadmill) scheduled for PCI, with SCr ≥ 1.5 mg/dl
63
82
221
41
22
Non vs SC
Iso-osmolar nonionic
298
2
Brar et al. [67]
353
Patients with stable renal disease and undergoing CAG
71
63.9
131.7
48
57
44.5
27.2
SC vs. SB
Ioxilan
132
5
353
Patients with stable renal disease and undergoing CAG
71
63.9
131.7
48
57
44.5
27.2
SC vs SB
Ioxilan
132
5
Adolph et al. [68]
145
Stable renal insufficiency and undergoing elective diagnostic or interventional coronary angiography
72.6
77.9
132.6
33.8
SC vs. SB
Iodixanol
140
5
145
Stable renal insufficiency and undergoing elective diagnostic or interventional coronary angiography
72.6
77.9
132.6
33.8
SC vs SB
Iodixanol
140
5
Schmidt et al. [69]
96
CAG
67.6
74
146.7
64.6
SC vs. SB
Optiray
186
2
96
CAG
67.6
74
146.7
64.6
SC vs SB
Optiray
186
2
Ozcan et al. [70]
264
Scheduled for CAG or PCI and had a baseline creatinine level >1.2 mg/dL
69
74.6
122.9
45.1
26.5
SC vs. SB
Ioxaglate
110
2
264
Scheduled for CAG or PCI and had a baseline creatinine level >1.2 mg/dL
69
74.6
122.9
45.1
26.5
SC vs SB
Ioxaglate
110
2
Masuda et al. [71]
59
Scheduled to undergo an emergency coronary angiography or intervention
75
44.1
116.2
30.5
SC vs. SB
Iopamidol
116
3
59
Scheduled to undergo an emergency coronary angiography or intervention
75
44.1
116.2
30.5
SC vs SB
Iopamidol
116
3
Dussol et al. [72]
156
CKD, who were undergoing radiological procedures with CM
65
67.9
204.5
33.1
28.8
16
SC vs. SC + diuresis
Nonionic, low osmolar
117
5
156
CKD, who were undergoing radiological procedures with CM
65
67.9
204.5
33.1
28.8
16
SC vs SC + diuresis
Nonionic, low osmolar
117
5
Mueller et al. [73]
425
Scheduled for elective or emergency PCI
64
75
89
16
0.45 SC vs. SC
Iopromide
226
2
425
Scheduled for elective or emergency PCI
64
75
89
16
0.45 SC vs SC
Iopromide
226
2
Merten et al. [74]
119
Stable renal insufficiency undergoing diagnostic or interventional procedures requiring radiographic contrast, SCr> 1.1 mg/dL
68
74.8
159.1
47.9
SC vs. SB
Iopamidol
132
3
119
Stable renal insufficiency undergoing diagnostic or interventional procedures requiring radiographic contrast, SCr> 1.1 mg/dL
68
74.8
159.1
47.9
SC vs SB
Iopamidol
132
3
Trivedi et al. [75]
53
Scheduled to undergo nonemergency CAG
67.9
98.1
106.4
52.1
18.9
Oral vs. SC
Ionic, low-osmolar
148
2
53
Scheduled to undergo nonemergency CAG
67.9
98.1
106.4
52.1
18.9
Oral vs SC
Ionic, low-osmolar
148
2
Mueller et al. [76]
1383
Scheduled for elective or emergency CAG
64
74.4
81.77
15.7
0.45 SC vs. SC
Ultravist or imeron
234
2
1383
Scheduled for elective or emergency CAG
64
74.4
81.77
15.7
0.45 SC vs SC
Ultravist, or imeron
234
2
CI-AKI: contrast-induced acute kidney injury; SCr: serum creatinine; eGFR: estimated glomerular filtration rate; LVEF: left ventricular ejection fraction; DM: diabetes mellitus; HF: heart failure; CM: contrast media; CTA: computed tomography angiography; TAVI: transcatheter aortic valve implantation; EVAR: elective endovascular aneurysm repair; AAA: abdominal aortic aneurysm; CKD: chronic kidney disease; CRT: cardiac resynchronization therapy; CTPA: computed tomography pulmonary angiography; PE: pulmonary embolism; CIN: contrast-induced nephropathy; CHF: chronic heart failure; CT: computed tomography; TAVR: transcatheter aortic valve replacement; CAG: coronary angiography; CE-CT: contrast media-enhanced computed tomography; CPB: cardiopulmonary bypass; PTCA: percutaneous transluminal coronary angioplasty; NAC: N-acetylcysteine. Treatment groups: SC: intravenous 0.9% sodium chloride; SB: intravenous sodium bicarbonate; Non: nonhydration; Oral: oral hydration; RenalGuard: RenalGuard system; HDy: hemodynamic guided hydration; SC + diuresis: intravenous 0.9% sodium chloride + diuresis; 0.45 SC: 0.45% sodium chloride.


## 3.3. Network Meta-Analysis

Figure2 shows all the comparisons in the NMA. Thirty-seven studies (13,365 participants) compared the efficacy of intravenous sodium bicarbonate and 0.9% sodium chloride. The other hydration strategies were nonhydration (8 studies, 1396 patients), oral hydration (6 studies, 355 patients), intravenous half iso-osmolar saline (3 studies, 968 patients), intravenous hydration, mainly normal saline + diuresis (2 studies [26, 31], 501 patients), hemodynamic guided hydration (3 studies, 458 patients), and RenalGuard system guided hydration (4 studies, 348 patients).Figure 2
Network diagram of eight hydration strategies used to prevent contrast-induced acute kidney injury in the 60 included studies. Circles represent hydration strategies and lines represent direct comparisons. Circle size indicates the number of participants who received each treatment, and line thickness indicates the number of studies in each comparison.We compared the ORs of the different hydration strategies using a forest plot (Figure3) and analyzed the results of the random effects consistency NMA using a league table, which shows all pairwise comparisons (Figure 4). Taken together, these results indicate that, relative to typical intravenous 0.9% sodium chloride hydration (reference), the occurrence of CI-AKI was significantly reduced by intravenous sodium bicarbonate (OR [95% CI]: 0.74 [0.57, 0.93]), hemodynamic guided hydration (0.41 [0.18, 0.93]), and RenalGuard system guided hydration (0.32 [0.14, 0.70]). Oral hydration (0.72 [0.28, 1.82]) and intravenous 0.9% sodium chloride (0.64 [0.39, 1.08]) were each noninferior to no hydration for prevention of CI-AKI. Relative to oral hydration (reference), intravenous 0.9% sodium chloride or sodium bicarbonate and hemodynamic guided hydration were each noninferior in prevention of CI-AKI, but RenalGuard guided hydration was superior (0.21 [0.07, 0.63]). Intravenous hydration plus diuresis also did not decrease the risk of CI-AKI relative to oral hydration and no hydration.Figure 3
Forest plot showing the effect of different hydration strategies. Summary estimates from the pooled studies with 95% confidence intervals are indicated for fixed effects (open diamonds) and random effects (filled diamonds) models.Figure 4
League table, showing all pairwise comparisons of studies.A rankogram and SUCRA values indicated the RenalGuard system was best (SUCRA = 0.974) followed by hemodynamic guided hydration (SUCRAs = 0.849; Figure5). Intravenous sodium bicarbonate had a SUCRA of 0.667. The SUCRAs for intravenous 0.9% sodium chloride, intravenous hydration plus diuresis, oral and no hydration, and the other treatments ranged from 0.197 to 0.441, and their rankings were similar. Hydration using half iso-osmolar saline alone was the least effective treatment.Figure 5
Rankogram of the effect of different hydration strategies in reducing the risk of contrast-induced acute kidney injury.


## 3.4. Inconsistency Analysis

We performed network inconsistency assessment for the fixed effect model for the 60 studies (Figure6). The resulting plot demonstrated that nearly all the studies were near the line of equality and that the results were therefore consistent. However, there was some evidence of inconsistency in 3 noninferiority studies [10, 31]. In particular, Martin-Moreno et al. [31] and Nijssen et al. [10] found that intravenous sodium bicarbonate and 0.9% sodium chloride were noninferior to oral hydration.Figure 6
Inconsistency plot of enrolled studies, showing the posterior mean deviance of each study from the consistency model (horizontal axis) and the inconsistency model (vertical axis).


## 4. Discussion

To our knowledge, this is the first NMA to compare different hydration strategies for prevention of CI-AKI. We included 60 RCTs which examined 21,293 participants and 2232 CI-AKI events. Our comparison of 8 hydration strategies for preventing CI-AKI confirmed that, relative to intravenous 0.9% sodium chloride hydration, three treatments during CM administration significantly reduced the risk for CI-AKI: the RenalGuard system, hemodynamic guided hydration, and intravenous sodium bicarbonate. Relative to no hydration, oral hydration and intravenous 0.9% sodium chloride were each noninferior in prevention of CI-AKI. Relative to oral hydration, intravenous 0.9% sodium chloride and sodium bicarbonate were each noninferior in prevention of CI-AKI. Thus, we ranked the RenalGuard system as the best strategy and hemodynamic guided hydration as the second best.Guidelines for the prevention of CI-AKI in high-risk patients routinely recommend hydration protocols before contrast exposure as an established preventive measure [77, 78]. A recent large RCT [10] led us to reanalyze the efficacy of hydration for prevention of CI-AKI. In particular, the AMAstricht Contrast-Induced Nephropathy Guideline (AMACING) study [10] enrolled 660 patients with high risk of CI-AKI and concluded that, relative to intravenous hydration, no prophylaxis was less expensive and noninferior in prevention of CI-AKI. In our meta-analysis, five studies compared the effectiveness of intravenous 0.9% sodium chloride and three studies compared bicarbonate with nonhydration, leading to our conclusion that, relative to no hydration (reference), oral hydration or hydration with intravenous 0.9% sodium chloride was noninferior in prevention of CI-AKI. These results were unsurprising, because simple oral or intravenous hydration can lead to complications, such as heart failure, pulmonary edema, and electrolyte disorders. Thus, the safety window of hydration is relatively narrow for patients undergoing percutaneous coronary intervention (PCI), and other more effective or precise hydration strategies may be needed to decrease the incidence of CI-AKI.Most meta-analyses before 2016 [79–83] confirmed that intravenous sodium bicarbonate was more effective than sodium chloride in preventing CI-AKI. However, two recent influential studies concluded that intravenous sodium bicarbonate provided no benefit over intravenous sodium chloride in high-risk patients [11] and critically ill patients [12]. Our NMA included 37 studies that compared intravenous sodium chloride with sodium bicarbonate, and our results also indicated that intravenous sodium bicarbonate led to a reduced risk for CI-AKI, although the effect size was small (OR [95% CI]: 0.74 [0.57, 0.93]). Alkalization with bicarbonate perfusion could theoretically reduce the formation of reactive oxygen species by decreasing the production of hydroxyl radicals due to inhibition of the Haber-Weiss and Fenton reactions [84]. However, the HYDRAREA study [12] assessed 307 critically ill patients with stable renal function and found that hydration with bicarbonate provided no benefit relative to hydration with isotonic sodium chloride. These researchers also noted that bicarbonate provided a greater benefit in the smaller studies, suggesting publication bias. Recently, Weisbord et al. [11] enrolled 5177 patients with high risk for renal complications and found that administration of sodium bicarbonate did not reduce the occurrence of CI-AKI. This result supports the interpretation that sodium bicarbonate is not more effective than sodium chloride in preventing CI-AKI or longer-term adverse outcomes after angiography. However, there was high heterogeneity among our 60 studies regarding concurrent medications, comorbidities (CHF, DM), types of CM, periprocedural hydration protocols, concentrations and dosages of sodium bicarbonate, and radiographic procedures [12]. Thus, we do not recommend alkalization with intravenous sodium bicarbonate as a single strategy, and a more effective hydration strategy is needed to prevent CI-AKI.Several recent RCTs of high risk patients [13, 28, 47, 55] showed that furosemide-induced high-volume forced diuresis with matched hydration using the RenalGuard system effectively prevented CI-AKI. RenalGuard is a closed-loop fluid-management system, in which each volume of urine that enters the collection bag leads to the infusion of an equal volume of saline into the patient. Two meta-analyses [14, 16] of RCTs concluded that the RenalGuard system significantly reduced the risk of CI-AKI and the need for renal replacement therapy in high-risk patients undergoing coronary angiography. Our rankogram analysis indicated that the RenalGuard system of guided hydration had the highest rank, with a SUCRA of 0.974. However, we did not assess the effectiveness of intravenous hydration plus diuresis without a guided system, and the rankogram indicated that hemodynamic guided hydration was the second best method, with a SUCRA of 0.849. Brar et al. [17] used left ventricular end-diastolic pressure to guide fluid administration and demonstrated that this method was safe and effective in prevention of CI-AKI among patients undergoing cardiac catheterization. Another study [19] demonstrated that central venous pressure-guided fluid administration safely and effectively reduced the risk of CI-AKI in patients with CKD and CHF. Maioli et al. [18] assessed body fluid level using bioimpedance vector analysis (BIVA), which allows adjustment of intravascular volume expansion, and this led to a lower incidence of CI-AKI after angiographic procedures. Therefore, our results indicate that the RenalGuard system and hemodynamic guided hydration are best for patients with high-risk for CI-AKI, especially those with CKD and cardiac dysfunction.


## 5. Limitations

It is essential to note several limitations of our study. Firstly, the hydration protocol should have a substantial influence on CI-AKI, but because of the high heterogeneity of specific protocols used in the included studies, we could not analyze distinct protocols, such as the effect of different concentrations of sodium bicarbonate, and the effect of hydration duration. Secondly, several confounding factors that we did consider may have impacted the effects of hydration, including dosage and types of CM, risk status of patients for CI-AKI, and other factors. Finally, it may be inappropriate to define hemodynamic guided hydration based on the use of different indexes, such as left ventricular end-diastolic pressure, central venous pressure, and bioimpedance.


## 6. Conclusion

This Bayesian NMA provided substantial evidence to support the use of RenalGuard or hemodynamic guided hydration to prevent CI-AKI in high-risk patients, especially those with CKD or cardiac dysfunction.



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*Source: 7292675-2020-02-11.xml*