Author and year

Reason for exclusion

Akyuz. 2014

Patients with normal kidney function

Alessandri, 2014

Patients with normal kidney function

Cho, 2010

Does not fulfill selection criteria

Heguilen, 2013

Not using the most widely used PC-AKI definition of SC rise ≥25% or 44µmol/l

Koc, 2013

Patients with normal kidney function

Kong, 2012

Patients with normal kidney function

Kotlyar, 2005

Does not fulfill inclusion criteria (compares iv hydration with N-acetylcysteïne to hydration with placebo, not different hydration strategies)

Lawlor, 2007

Mixture of oral and intravenous hydration, compared to intravenous hydration alone

Mahmoodi, 2014

Patients with normal kidney function

Manari, 2014

The studied hydration infusion mixture is not used in Dutch clinical practice

Martin-Moreno, 2015

Patients with normal kidney function

Mueler, 2005

Does not fulfill inclusion criteria (no control group)

Pakfetrat, 2009

The studied hydration infusion mixture is not used in Dutch clinical practice

Taylor, 1998

Mixture of oral and intravenous hydration, compared to intravenous hydration alone

Thayssen, 2014

Patients with normal kidney function

Trivedi, 2003

Normal kidney function

Vashegani Ferahani, 2009

The studied hydration infusion mixture is not used in Dutch clinical practice

Wrobel, 2014

Did not define CIN/CI-AKI/PC-AKI

Yeghanehkah, 2014

The studied hydration infusion mixture is not used in Dutch clinical practice

Study reference

(first author, publication year)

Describe method of randomisation¹

Bias due to inadequate concealment of allocation?²

(unlikely/likely/unclear)

Bias due to inadequate blinding of participants to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of care providers to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of outcome assessors to treatment allocation?³

(unlikely/likely/unclear)

Bias due to selective outcome reporting on basis of the results?⁴

(unlikely/likely/unclear)

Bias due to loss to follow-up?⁵

(unlikely/likely/unclear)

Bias due to violation of

intention to treat analysis?⁶

(unlikely/likely/unclear)

Hydration versus no hydration

Kooiman, 2014

Computer generated allocation sequence

(stratified by hospital and renal function)

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Nijssen, 2017

Computer- generated using ALEA screening and enrolment application software.

Unlikely

Likely

Likely

Unlikely

Unlikely

Unlikely

Unlikely

Oral hydration

Cho, 2010

Not decribed: “randomly assigned”

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unclear

Unclear

Dussol, 2006

Computer generated randomization list

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unclear

Sodium bicarbonate short schedule versus saline short schedule for coronary angiography and/or percutaneous intervention

Adolph, 2008

Computer-generated randomization schedule

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unclear

Unclear

Boucek, 2013

Computer-generated randomization schedule with the use of numbered opaque envelopes containing identification of assigned medication

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unclear

Brar, 2008

Computer-generated randomization schedule

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unclear

Gomes, 2012

Not decribed: “randomly assigned”

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unclear

Unlikely

Huber, 2016

Computer-generated randomization

list

Unlikelu

Unlikely

Unlikely

Unlikely

Unlikely

Unclear

Unclear

Manari, 2014

Computer generated balanced randomization list

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unclear

Unclear

Ozcan, 2007

Not decribed: “randomly assigned”

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unclear

Unclear

Ratcliffe, 2009

Not decribed: “randomization block”

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Likely

Unclear

Recio-Mayoral, 2007

Not decribed: “randomly assigned”

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unclear

Unlikely

Sodium bicarbonate short schedule versus saline long schedule for coronary angiography and/or percutaneous intervention

Briguori, 2007

Computer-generated randomization schedule

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unclear

Castini, 2008

Computer-generated randomization table

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unclear

Unclear

Hafiz, 2012

Random allocation table

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unclear

Klima, 2012

Sealed envelopes

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unclear

Lee, 2011

Interactive web response system, computer generated randomization, stratified by participating center

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unclear

Maioli, 2008

Computerized open-label assignment in blinded envelopes used in a consecutive fashion

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unclear

Nieto-Rios, 2014

Sealed opaque envelopes (random numbers table)

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unclear

Shavit, 2009

Not described

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unclear

Sodium bicarbonate versus saline: “other schedules” for coronary angiography and/or percutaneous intervention

Chong, 2015

Block randomisation,

stratified by site, using aweb-randomisation system or back-up randomisation envelopes.

Unlikely

Likely

Unclear

Unlikely

Unlikely

Unlikely

Unlikely

Motohiro, 2011

Computer-generated random numbers

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Tamura, 2009

Computer-generated random numbers

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Turedi,

2016

Computer-based block randomization.

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unclear

Unlikely

Ueda, 2011

Computer-generated random numbers

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Sodium bicarbonate short schedule versus saline long schedule for computed tomography

Kooiman, 2014

Computer-generated allocation sequence

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Controlled diuresis

Brar, 2014

Computer-generated concealed randomisation schedule

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Barbanti, 2015

Randomization based on computer generated

codes

Unlikely

Likely

Likely

Unlikely

Unlikely

Unlikely

Unlikely

Briguori, 2011

Computer-generated randomisation list

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unclear

Marenzi, 2012

Computer-generated random numbers

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unclear

Qian, 2016

“randomly assigned”

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unclear

Usmiani, 2015

“randomly assigned”

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unclear

Usmiani, 2016

Randomly subdivided

Unlikely

Likely

Likely

Unlikely

Unlikely

Unclear

Unlikely

Visconti, 2016

Prospective, non-randomised study

Likely

Unclear

Unclear

Unclear

Unlikely

Unclear

Unclear

Study reference

Study characteristics

Patient characteristics ²

Intervention (I)

Comparison / control (C) ³

Follow-up

Outcome measures and effect size ⁴

Comments

Hydration versus no hydration

Kooiman, 2014

Type of study: randomized controlled trial

Setting: emergency patients, multiple centers, both in- and outpatients

Country: the Netherlands

Source of funding: non-commercial

Inclusion criteria:

1) adult patients ≥18 years with a clinical suspicion of a pulmonary embolis requiring computed tomography-pulmonary angiography (CTPA)

2) chronic kidney disease (CKD): eGFR <60mL/min/1.73m²

Exclusion criteria:

1) pregnancy

2) previous contrast administration within past 7 days

3) documented allergy for iodinated contrast media

4) hemodynamic instability (systolic blood pressure <100mmHg)

5) earlier participation in samen trial

N total at baseline:

Intervention: 67

Control: 71

Important prognostic factors²:

For example

age ± SD:

I: 70 ± 12

C: 71 ± 13

Sex:

I: 52% M

C: 48% M

eGFR ± SD:

I: 50 ± 16

C: 48 ± 15

Groups comparable at baseline?

Yes

Describe intervention (treatment/procedure/test):

Withholding hydration prior to CTPA

Describe control (treatment/procedure/test):

250mL iv 1.4% sodium bicarbonate 1 hour before CTPA

Length of follow-up:

96 hours

Loss-to-follow-up:

3/138 (2.2%)

2 lost to follow-up

1 died

Incomplete outcome data:

As above

Outcome measures and effect size (include 95%CI and p-value if available):

CI-AKI

(= creatinine increase >25% / >0.5mg/dL)

I: 6 (9%)

C: 5 (7%)

RR: 1.29, 95% CI: 0.41 – 4.03

None of the patients developed a need for dialysis

Authors’ conclusion:

Our results suggest that preventive hydration could be safely withheld in CKD patients undergoing CTPA for suspected acute pulmonary embolism.

Nijssen, 2017

(AMACING)

Type of study: randomized controlled trial

Setting: elective patients, one university hospital

Country: the Netherlands

Source of funding: Stichting de Weijerhorst

Inclusion criteria:

1) eGFR: 45-59 mL/min/1.73m² combined with either diabetes, or at least two predefined risk factors (age>75y; anaemia defined as haematocrit values <0.39L/L for men, and <0.36L/L for women; cardiovascular disease; non-steroidal anti-inflammatory drug; or diuretic nephrotoxic medication).

Exclusion criteria:

1) Inability to obtain informed consent;

2) eGFR lower than 30mL per min/1.73m²;

3) renal replacement therapy; 4)emergency procedures;

5) intensive care patients;

6) known inability to perform primary endpoint data collection;

7) no referral to prophylactic hydration;

8) participation in other RCT; and

9) isolation due to infection control

N total at baseline:

Intervention: 328

(I1: 328, I2: 296)

Control: 332

(C1: 332, C2: 307)

Important prognostic factors²:

For example

age ± SD:

I: 71.9 ± 9.3

C: 72.6 ± 9.3

Sex:

I: 59% M

C: 64% M

Baseline SCr:

I:118.7±28μmol/L

C:117.7±25μmol/L

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

Prophylactic hydration protocols according to current guidelines:

Standard protocol intravenous

0.9% NaCl 3–4 mL/kg per h during 4 h before and 4 h

after contrast administration; long protocol intravenous

0.9% NaCl 1 mL/kg per h during 12 h before and 12 h after

contrast administration.

Describe control (treatment/procedure/test):

No prophylactic treatment.

Length of follow-up:

2-6 days

Loss-to-follow-up:

I: 68/328

C: 25/332

Incomplete outcome data:

As above

Outcome measures and effect size (include 95%CI and p-value if available):

CI-AKI

(25% or 44 μmol/L within 2–6 days of contrast exposure)

I:8 (2.7%)

C: 8 (2.6%)

P=0.417

No hydration was cost-saving relative to hydration.

No haemodialysis or related deaths occurred within

35 days.

Authors’ conclusion:

‘We found no prophylaxis to be non-inferior and cost-saving in preventing contrast-induced nephropathy

compared with intravenous hydration according to current clinical practice guidelines.’

Oral hydration

Cho, 2010

Type of study: randomized controlled trial

Setting: elective patients, one hospital

Country: United States of America

Source of funding: not reported

Inclusion criteria:

1) patients 18 years or older with stable serum creatinine levels of at least 1.1mg/dL or estimated creatinine clearance less than 60mL/min scheduled for diagnostic, elective angiography

Exclusion criteria:

1) serum creatinine levels >8.0mg/dL

2) change in serum creatinine levels of at least 0.5mg/dL during the previous 24 hours

3) pre-existing dialysis

4) multiple myeloma or other myeloproliferative disease

5) current decompensated heart failure or significant change in NYHA

6) current myocardial infarction

7) symptomatic hypokalaemia

8) uncontrolled hypertension

9) exposure to radiocontrast within 7 days of enrolment into this study

10) emergency catheterisation

11) allergy to radiographic contrast

12) pregnancy

13) administration of mannitol, feoldapam or NAC during the time of the study

14) exacerbation of chronic obstructive pulmonary disease

15) serum bicarbonate greater than 28eEw/L and sodium less than 133mEq/L

N total at baseline:

Intervention: 43

(I1: 22, I2: 22)

Control: 48

(C1: 27, C2: 21)

Important prognostic factors²:

For example

age ± SD:

I1: 81 ± 7

I2: 79 ± 2

C1: 77 ± 8

C2: 78 ± 9

Sex:

I1: 45% M

I2: 38% M

C1: 63% M

C2: 52

Baseline SCr:

I1: 1.38

I2: 1.31

C1: 1.38

C2: 1.41

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

1) oral hydration with 500mL of water to be started 4 hours prior to contrast exposure and stopped 2 hours prior to procedure followed by oral hydration with 600mL water postprocedure

2) oral hydration with 500mL of water to be started 4 hours prior to procedure and stopped 2 hours prior to contrast exposure, with the addition of 3.9g (46.4mEq) of oral sodium bicarbonate to be given 20 minutes prior to contrast exposure followed by oral hydration with 600mL of water and 1.95g (30.4mEq) of oral sodium bicarbonate 2 hours and 4 hours after the initial dose

Describe control (treatment/procedure/test):

1) pretreatment with a 3mL/kg bolus of intravenous saline solution (154mEq/L) over 1 hour priori to contrast exposure

Intravenous infusion of 1mL/kg for 6 hours after procedure

2) pretreatment with a 3mL/kg bolus of intravenous sodium biacrbonate solution (154mEq/L) over 1 hour priori to contrast exposure

Intravenous infusion of 1mL/kg for 6 hours after procedure

Length of follow-up:

72 hours

Loss-to-follow-up:

Not reported

Incomplete outcome data:

Not reported

Outcome measures and effect size (include 95%CI and p-value if available):

CIN

(= >25% increase in sCr from baseline or an absolute increase of 0.5mg/dL from baseline at 72 hours following exposure to radio-contrast)

I1: 1/22

I2: 1/22

C1: 6/27

C2: 2/21

p>0.05

There were no in-hospital mortalities during this study.

Length of hospital stay did not differ significantly between groups.

Authors’ hydration:

Oral hydration with or without sodium bicarbonate prior to and following CAG is not inferioir to intravenous hydration and sodium bicarbonate with respect to CIN; and to date, offers an equivalent and practical approach in preventing a decline in renal functionafter contrast exposure without accuring additional delay in hospital days or in-hospital mortality,

Dussol, 2006

Type of study: randomized controlled trial

Setting: elective patients, one university hospital

Country: France

Source of funding: non-commercial

Inclusion criteria:

1) patients referred for any radiological procedures necessitating a contrast medium injection and who had a baseline Cockcroft clearance between 15-60ml/min

2) either chronic renal failure and on a kidney graft

Exclusion criteria:

1) <18 years old

2) women of child-bearing age not using contraception or breast feeding

3) patients with heart failure and ejection fraction <30%

4) uncontrolled arterial hypertension

5) obvious extracellular overhydration

6) respiratory depression

7) known prior intolerance to theophylline or furosemide

8) previous exposure to contrast media in the 14 days before randomization

9) unwilling or unable to provide informed consent

10) adequate time prior to contrast media injection was not available to perform the study procedure

11) if sCr measurements varied by >10% in the previous weeks before referral

N total at baseline:

Intervention:

Control:

Important prognostic factors²:

For example

age ± SD:

I: 63 ± 15

C: 64 ± 11

Sex:

I: 66% M

C:75 % M

eGFR ± SD:

I: 38 ± 13

C: 33 ± 11

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

NaCl 1g/10kg/day per os for 2 days

Describe control (treatment/procedure/test):

0.9% saline iv 15ml/kg for 6 hours before the procedure

Length of follow-up:

48 hours

Loss-to-follow-up:

Not reported per group separately, in total 3/315 (1%) lost to follow-up

Incomplete outcome data:

As above

Outcome measures and effect size (include 95%CI and p-value if available):

CIN

(= increase in the baseline sCr concentration of at least 44µmol/L (0.5mg/dL) within 48 hours after the injection of contrast media)

I: 5/76 (7%)

C: 4/77 (5%)

p>0.05

None of the patients had fluid overload

Authors’ conclusion:

Oral saline hydration was as efficient as intravenous saline hydration for the prevention of CIN in patients with stage 3 renal diseases.

Sodium bicarbonate short schedule versus saline short schedule for coronary angiography and/or percutaneous intervention

Adolph, 2008

Type of study: randomized controlled trial

Setting: elective patients

Country: Germany

Source of funding: not reported

Inclusion criteria:

1) patients >18 years with baseline serum creatinine concentration greater than 106µmol/L (1.2mg/dL) undergoing elective diagnostic or interventional coronary angiography

Exclusion criteria:

1) acute myocardial infarction

2) allergies to trial medication

3) exposure to contrast mediumwithin the last 7 days

4) thyroid dysfunction

5) pregnancy

6) uncontrolled hypertension

7) life-limiting concomitant disease

8) pulmonary edema

9) chronic dialysis

10) administration of dopamine, mannitol, fenoldopam or NAC during the study

N total at baseline:

Intervention: 71

Control: 74

Important prognostic factors²:

For example

age ± SD:

I: 70 ± 8

C: 73 ± 7

Sex:

I: 75% M

C: 81% M

sCr (mg/dL ± SD)

I: 1.54 ± 0.51

C: 1.57 ± 0.36

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

Sodium bicarbonate 154mEq/L in 5% dextrose solution

2ml/kg body weight/hour for 2 hours before

And

1ml/kg body weight/hour during and for 6 hours after contrast administration

Describe control (treatment/procedure/test):

Sodium chloride 154 mEq/L in 5% dextrose solution

2ml/kg body weight/hour for 2 hours before

And

1ml/kg body weight/hour during and for 6 hours after contrast administration

Length of follow-up:

2 days

Loss-to-follow-up:

1 patient (refused follow-up)

Incomplete outcome data:

3/145 (2%)

2 patients had an emergency coronary bypass and pulmonary edema

1 patient refused follow-up

Outcome measures and effect size (include 95%CI and p-value if available):

CIN

(= elevation of sCr concentration >0.5mg/dL (44µmol/L) or 25%above baseline between day 0 and days 1 or 2 after contrast axposure)

I: 4.2%

C: 2.7%

P=0.61

Dialysis for acute renal failure was not required

Authors’ conclusion:

Renal Insufficiency following radiocontrast exposure demonstrates a homogenously low rate of CIN after exposure to non-ionic, iso-osmolar iodixanol regardless of the use of either bicarbonate sodium or sodium chloride solution for volume supplementation.

Boucek, 2013

Type of study: RCT

Setting: elective inpatients, one hospital

Country: Czech Republic

Source of funding: commercial

Inclusion criteria:

1) presence of diabetes mellitus

2) renal function

impairment (screening serum creatinine _100 mmol/L),

3) age of

≥18 years

4) a planned procedure with intra-arterial or

intravenous use of contrast

Exclusion criteria:

1) endstage

renal disease (screening serum creatinine _500 mmol/L,

2) chronic dialysis treatment or presence of kidney transplant),

3) pre-planned dialysis following the contrast-involving procedure,

4) emergency type of procedure, acute kidney injury

(serum creatinine increase _50 mmol/L during the previous

24-h period),

5) volume overload with left ventricular failure,

6) uncontrolled hypertension (systolic BP _180 or diastolic BP

_110 mmHg),

7) hemodynamic instability (systolic BP <90 and

diastolic BP <50 mmHg),

8) contrast use in the previous 48-h

period,

9) multiple myeloma,

10) pregnancy or breastfeeding

11) pre-planned use of any other measure for CIN prevention

apart from the NaCl or NaHCO3 infusions

N total at baseline:

Intervention: 61

Control: 59

Important prognostic factors²:

For example

age ± SD:

I: 63 ± 11

C: 67 ± 10

Sex:

I: 75% M

C: 75% M

eGFR (mL/min/1.73m²) ± SD

I: 44 ± 19

C: 25 ± 17

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

1.4% sodium bicarbonate in 5% glucose

3ml/kg/hour 1 hour before contrast administration (limited to a maximum of 330mL)

1mL/kg/hour 6 hours after contrast administration

(limited to a maximum of 660mL)

Describe control (treatment/procedure/test):

0.9% saline in 5% glucose

3ml/kg/hour 1 hour before contrast administration (limited to a maximum of 330mL)

1mL/kg/hour 6 hours after contrast administration

(limited to a maximum of 660mL)

Length of follow-up:

2 days – laboratory parameters

1 month – clinical parameters

Loss-to-follow-up:

Intervention:

3/61 (5%)

Reasons not described

Control:

3/59 (5%)

Reasons not described

Incomplete outcome data:

As above

Outcome measures and effect size (include 95%CI and p-value if available):

CIN

(= sCr increase of ≥25% and/or 44µmol/L (0.5mg/dL) within 2 days foillowing administration of contrast)

I: 7 (12%)

C: 5 (9%)

P=0.76

Incidence rate ratio: 1.35 (95% CI: 0.37 – 5.41)

No patients died or experienced severe kidney injury with need for acute dialysis treatment.

Authors’ conclusion:

In diabetic patients with renal function impairment sodium bicarbonate does

not confer protection against contrast-induced nephropathy greater than sodium chloridebased

hydration.

Brar, 2008

Type of study: randomized controlled trial

Setting: elective patients, one hospital

Country: United States of America

Source of funding: commercial

Inclusion criteria:

1) an estimated

glomerular filtration rate (GFR) of 60 mL/min per 1.73m2 or less,

2) age 18

years or older,

3) at least 1 of the follwing: -diabetes mellitus,

-history of congestive heart failure,

-hypertension (140/90 mm Hg treatment with an antihypertensive medication),

-age older than 75 years

Exclusion criteria:

1) inability to obtain consent, 2) receipt of a sodium bicarbonate

infusion prior to randomization,

3) emergency cardiac catheterization,

4) intra-aortic balloon counterpulsation,

5) dialysis,

6) exposure to radiographic

contrast media within the preceding 2 days,

7) allergy to radiographic

contrast media,

8) acutely decompensated

congestive heart failure,

9) severe valvular abnormality (eg, severe aortic stenosis or

mitral regurgitation),

10) single functioning

kidney,

11) history of kidney or heart transplantation,

12) change in estimated GFR of 7.5% or more per day or a cumulative change of15%or more over the prior 2 or more days

N total at baseline:

Intervention: 175

Control: 178

Important prognostic factors²:

For example

age (IQR range)

I: 71 (65-75)

C: 71 (65-76)

Sex:

I: 65% M

C: 62% M

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

1.4% sodium bicarbonate iv infusion

Infusion was begun 1

hour prior to the start of contrast administration

at3mL/kg for1hour, decreased

to 1.5 mL/kg per hour during the procedure

and for 4 hours following completion

of theprocedure.Forpatientsweighing

more than 100 kg, the bolus and infusion

rate were limited to those used for

patients weighing100kg

Describe control (treatment/procedure/test):

0.9% saline iv infusion

Infusion was begun 1

hour prior to the start of contrast administration

at3mL/kg for1hour, decreased

to 1.5 mL/kg per hour during the procedure

and for 4 hours following completion

of theprocedure.Forpatientsweighing

more than 100 kg, the bolus and infusion

rate were limited to those used for

patients weighing100kg

Length of follow-up:

2-3 days for laboratory parameters

6 months for clinical effects

Loss-to-follow-up:

Intervention:

17 (10%) Excluded

1 Did not undergo coronary angiography

16 Did not have estimated GFR data

1-4 d after procedure

Control:

13 (7%) Excluded

2 Did not undergo coronary angiography

11 Did not have estimated GFR data

1-4 d after procedure

Incomplete outcome data:

As above for laboratory paramters.

All patients were followed up for clinical events.

Outcome measures and effect size (include 95%CI and p-value if available):

≥25% reduction in estimated eGFR

I: 21/158 (13%

C: 24/165 (15%)

Absolute difference: 1.3, 95% CI: -6.3 to 8.8, p=0.75

Serum creatinine >25% or >0.5mg/dL increase

I: 26/158 (17%)

C: 30/165 (18%)

Absolute difference: 1.7, 95% CI: -6.5 to 10.0, p=0.78

30-day mortality

I: 3/175 (2%)

C: 3/178 (2%)

p>0.05

6-month mortality

I: 34%

C: 2%

P=0.54

6-month start of dialysis

I: 2/175 (1%)

C: 4/178 (2%)

P-value not reported

Authors’ conclusion:

The results of this study do not suggest that hydration with sodium bicarbonate

is superior to hydration with sodium chloride for the prevention of contrast

medium–induced nephropathy in patients with moderate to severe chronic kidney disease

who are undergoing coronary angiography.

Gomes, 2012

Type of study: randomized controlled trial

Setting: elective patients, 6 difference centres

Country: Brazil

Source of funding: none reported

Inclusion criteria:

1) patients at moderate to high risk for developing CIN who were referred for elective coronary angiography or PCI at 6 centers

2) serum creatinine ≥ 1.2 mg/dL or glomerular filtration rate (GFR) <50 mL/min

Exclusion criteria:

1) age <18 years,

2) use of radiographic contrast media during the last 21 days,

3) history of dialysis,

4) cardiac insufficiency class III-IV NYHA,

5) emergency procedures

N total at baseline:

Intervention: 150

Control: 151

Important prognostic factors²:

For example

age ± SD:

I: 64 ± 12

C: 65 ± 12

Sex:

I: 69% M

C: 75% M

eGFR ± SD

I: 51 ± 13

C: 52 ± 13

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

154 mEq/l of sodium bicarbonate in 5% dextrose and H₂O

3 mL/ kg/ h for 1 hour immediately before contrast injection

same fluid at a rate of 1 mL/kg/h during contrast exposure and for 6 hours after the procedure

Describe control (treatment/procedure/test):

0.9% saline infusion

3 mL/ kg/ h for 1 hour immediately before contrast injection

same fluid at a rate of 1 mL/kg/h during contrast exposure and for 6 hours after the procedure

Length of follow-up:

48 hours

Loss-to-follow-up:

Not reported

Incomplete outcome data:

Not reported

Outcome measures and effect size (include 95%CI and p-value if available):

CIN

(=an increase in serum creatinine ≥ 0.5 mg/dL 48 hours after exposure to contrast medium)

I: 9/150 (6%)

C: 9/151 (6%)

P=0.97

Dialysis:

I: 0%

C: 0%

P=1.00

Death:

I: 3%

C: 5%

P=0.81

Authors’ conclusion:

Hydration with sodium bicarbonate was not superior to saline to prevent contrast media induced nephropathy in patients at risk undergoing cardiac catheterization.

Huber, 2016

Type of study: randomized controlled

Setting: single-center university hospital

Country: Germany

Source of funding: institutional support

Inclusion criteria:

1) >18 years;

2) increased risk of CIN undergoing administration of CM. High risk was

defined by a serum creatinine level ≥1.1 or ≥0.8 mg/dL plus an

additional risk factor like diabetes mellitus, renal failure in past

medical history, or nephrotoxic medication (aminoglycoside,

vancomycin, amphotericin B, and diuretic).

Exclusion criteria:

1) pre-existing renal replacement therapy;

2) unstable serum

creatinine levels (difference of more than _0.4 mg/dL within 3

days before contrast application);

3) contraindi-cations for theophylline

or sodium bicarbonate (allergies, tachycardia, alkalosis,

and hypokalemia); and;

4) additional interventions that might

influence renal function.

Important prognostic factors²:

For example

age ± SD:

I: 64.4 ± 15.7

C: 66.1 ±13.3

Sex:

I: 59.5% M

C: 66.7% M

Baseline SCr:

I:1.25± 0.69 mg/dL

C:1.38± 0.65 mg/dL

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

Group B received bicarbonate infusion with 200mg theophylline.

Describe control (treatment/procedure/test):

Control group S received sodium chloride infusion with 200mg theophylline.

Length of follow-up:

48h after CM

Loss-to-follow-up:

I:14/91

C: 14/94

Incomplete outcome data:

Not reported

Outcome measures and effect size (include 95%CI and p-value if available):

CIN

as a raise in serum creatinine of _25% or _0.5 mg/dL within 48 h after contrast application

I: 1/74 (1.4%)

C: 7/78 (9%)

P=0.039

Dialysis:

I: 9%

C: 17%

P=0.189

Authors’ conclusion:

‘In patients at increased risk of CIN receiving prophylactic theophylline,

hydration with sodium bicarbonate reduces contrast-induced renal

impairment compared to hydration with saline.’

Manari, 2014

Type of study: randomized controlled

Setting: emergency patients, multicentre trial

Country: Italy

Source of funding: not reported

Inclusion criteria:

1) Patients

with STEMI within 12 h from symptom onset referred

for primary angioplasty

2) age at least 18 years

3) chest pain lasting for at least 30 min associated with STsegment

elevation of 0.2mV or more in at least two

contiguous leads or new left bundle-branch block

Exclusion criteria:

1) the concomitant detection of mechanical complications,

2) previous peritoneal or hemodialysis treatment, 3) the presence of postanoxic coma

4) pregnancy

N total at baseline:

Intervention 1: 145

Intervention 2: 154

Control 1: 142

Control 2: 151

Important prognostic factors²:

For example

age ± SD:

I1: 64 ± 13

I2: 65 ± 13

C1: 65 ± 13

C2: 65 ± 12

Sex:

I1: 72% M

I2: 75% M

C1: 75% M

C2: 77% M

eGFR ml/min

I1: 80 ± 26

I2: 82 ± 24

C1: 81 ± 23

C2: 82 ± 25

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

I1:

sodium bicarbonate solution 1 ml/kg of body weight per hour for 12 h

I2:

3 ml/kg of body weight per hour for 1 h, followed by

1 ml/kg of body weight per hour for 11 h

Describe control (treatment/procedure/test):

C1:

Intravenous normal saline (0.9%) at a rate of 1 ml/kg of body

weight per hour for 12 h

C2:

normal saline at a

rate of 3 ml/kg of body weight per hour for 1 h followed by

1 ml/kg of body weight per hour for 11 h

Length of follow-up:

3 days – laboratory parameters

12 months – clinical events

Loss-to-follow-up:

Not reported

Incomplete outcome data:

Not reported

Outcome measures and effect size (include 95%CI and p-value if available):

sCr increase ≥25% compared to baseline

I1: 24 (16%)

I2: 27 (18%)

C1: 29 (19%)

C2: 27 (19%)

P=0.92

sCr increase ≥0.5 mg/dL from baseline

I1: 5 (3%)

I2: 3 (3%)

C1: 7 (5%)

C2: 8 (6%)

P=0.51

Mortality did not differ at 30 days and at 12 months (data not shown).

Authors’ conclusion

In patients with STEMI undergoing PPCI, highvolume

hydration with normal saline or sodium bicarbonate

administrated at the time of contrast media administration

was not associated with any significant advantage in terms

of CI-AKI prevention.

Ozcan, 2007

Type of study: randomized controlled trial

Setting: elective patients

Country: Turkey

Source of funding: not reported

Inclusion criteria:

patients who were scheduled

for coronary angiography or percutaneous coronary intervention

and had a baseline creatinine level N1.2 mg/dL

Exclusion criteria:

1) uncontrolled hypertension (systolic and diastolic blood pressure N160 mm Hg and N110 mm Hg, respectively),

2) emergency catheterization,

3) recent exposure to radiocontrast medium within 2 days,

4) volume overload,

5) serum creatinine

levels >4 mg/dL

N total at baseline:

Intervention: 88

Control: 88

Important prognostic factors²:

For example

age median (minimum – maximum)

I: 68 (43-86)

C: 70 (40-84)

Sex:

I: 73% M

C: 75% M

Creatinine clearance (mL/min)

I: 53 (21 – 81)

C: 50 (22-101)

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

1.4% sodium bicarbonate

Iv fluid (1 mL/kg/h,

upper limit 100 mL/h) for 6 hours before and 6 hours after the procedure

Describe control (treatment/procedure/test):

0.9% saline

Iv fluid (1 mL/kg/h,

upper limit 100 mL/h) for 6 hours before and 6 hours after the procedure

Length of follow-up:

48 hours

Loss-to-follow-up:

Not reported

Incomplete outcome data:

Not reported

Outcome measures and effect size (include 95%CI and p-value if available):

CIN

(=an increase in

serum creatinine N25% or 0.5 mg/dL after 48 hours)

I: 12/88

C: 4/88

P=0.043

RR (adjusted): 0.29

95% CI: 0.09 – 0.96

Authors’ conclusion

Hydration with sodium bicarbonate provides better protection against CIN than the sodium chloride

infusion does alone.

Ratcliffe, 2009

Type of study: randomized controlled trial

Setting: elective patients, 1 center

Country: United States of America

Source of funding: not reported

Inclusion criteria:

1) ambulatory or hospitalized patients who were scheduled for invasive coronary angiography or percutaneous coronary intervention for the evaluation and treatment of coronary artery disease

2) willing to participate

in the study, and were able to understand and provide

informed written consent

3) patients older than 18 years of age, with renal insufficiency defined by elevated serum creatinine (greater than 132.6 μmol/L

in men, and greater than 114.9 μmol/L in women) or reduced calculated creatinine clearance (less than 1.002 mL/s) using the

Cockcroft-Gault formula, and/or diabetes mellitus on oral antiglycemic or insulin therapy

Exclusion criteria:

1) pregnancy or lactation; 2) acute myocardial infarction;

3) clinical signs of heart failure (or documented ejection fraction of less than 35%);

4) cardiogenic shock; 5) hypertrophic or restrictive cardiomyopathy;

6) contrast medium exposure within one week before the procedure;

7) previous serious reactions to contrast medium;

8) renal transplantation; dialysis; severe comorbid illness;

9) use of dopamine, mannitol or fenoldopam; 10) newly discovered uncontrolled diabetes mellitus;

11) the inability to obtain informed consent or follow-up

N total at baseline:

Intervention:

Control:

Important prognostic factors²:

For example

age ± SD:

I: 67 ± 11

C: 64 ± 10

Sex:

I: 58% M

C: 60% M

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

Iv 0.9% NaHCO3 hydration

at an infusion rate of

3 mL/kg/h for 1 h before contrast, and continued at 1 mL/kg/h during the procedure and for 6 h following contrast exposure

Describe control (treatment/procedure/test):

Iv 0.9% saline hydration

at an infusion rate of

3 mL/kg/h for 1 h before contrast, and continued at 1 mL/kg/h during the procedure and for 6 h following contrast exposure

Length of follow-up:

72 hours

Loss-to-follow-up:

Intervention:

15/30 (50%)

Reasons:

11 lack of complete follow-up

4 other reasons

Control:

10/29 (30%)

8 lack of complete follow-up

2 other reasons

Incomplete outcome data:

As above

Outcome measures and effect size (include 95%CI and p-value if available):

CIN

(=an increase of greater than 25% in serum creatinine concentration from baseline to 72 h after administration of the contrast media)

I: 2/19 (11%)

C: 1/15 (7%)

p>0.05

Authors’ conclusion:

CIN in high-risk patients may be effectively minimized solely through the use of an aggressive hydration protocol and an iso-osmolar contrast agent. The addition of NaHCO3 and/or NAC did not have an effect on the incidence of CIN.

Recio-Mayoral, 2007

Type of study: randomized controlled trial

Setting: emergency patients, one hospital

Country: United Kingdom

Source of funding: not reported

Inclusion criteria:

1) acute coronary syndrome (ACS) patients who were admitted to our coronary care unit

2) patients with myocardial infarction treated with primary PCI or rescue PCI, as well as patients with high-risk non–ST-segment elevation ACS needing urgent revascularization

Exclusion criteria:

1) end-stage renal failure on dialysis,

2) uncontrolled hypertension (systolic blood pressure

>160 mm Hg and/or diastolic blood pressure >100 mm Hg)

3) signs of cardiac failure not responding to medical treatment,

4) known severe aortic valve stenosis (area >1.0 cm2),

5) allergy to iodated contrast or NAC 6) pregnancy

N total at baseline:

Intervention: 56

Control: 55

Important prognostic factors²:

For example

age ± SD:

I: 65 ± 10

C: 64 ± 9

Sex:

I: 68% M

C: 71% M

Glomerular filtration rate (mL/min)

I: 75 ± 21

C: 74 ± 20

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

Active prophylactic treatment of PCI:

Intravenous bolus of 5 ml/kg/h of alkaline saline solution with 154 mEq/l of sodium bicarbonate in 5% glucose and H2O (adding 77 ml of 1,000 mEq/l sodium bicarbonate to 433 ml of 5% glucose in H2O) plus 2,400 mg of N-AC in the same solution over 1 hour the bolus was administered

in the 60 min preceding contrast injection

Afterward, patients received fluid therapy, without N-AC, at 1.5 ml/kg/h perfusion rate in the 12 h after the procedure plus 2 doses of 600 mg N-AC orally the next day

Describe control (treatment/procedure/test):

Standard treatment:

perfusion of isotonic saline (0.9%) at rate of 1 ml/kg/h for 12 h after PCI plus 2 doses of 600 mg N-AC orally the next day

Length of follow-up:

3 days

Loss-to-follow-up:

Not reported

Incomplete outcome data:

Not reported

Outcome measures and effect size (include 95%CI and p-value if available):

CIN

(=an absolute increase in SCr concentration

of 0.5 mg/dl or more from baseline value in the 3 days after

PCI)

I: 1/55 (2%)

C: 12/55 (22%)

Odds ratio: 0.065 (95% CI: 0.008 – 0.521, p=0.01)

Acute anuric renal failure

I: 1/55 (2%)

C: 7/55 (13%)

P=0.032

Authors’ conclusion:

Rapid intravenous hydration with sodium bicarbonate plus N-AC before contrast injection is effective and safe in

the prevention of CIN in patients undergoing emergency PCI.

Sodium bicarbonate short schedule versus saline long schedule for coronary angiography and/or percutaneous intervention

Briguori, 2007

Type of study: randomized controlled trial

Setting: elective patients, one hospital

Country: Italy

Source of funding: not reported

Inclusion criteria:

1) patients with chronic kidney disease who underwent coronary and/or peripheral angiography and/or angioplasty

2) _18 years of age

3) stable serum creatinine concentration >2.0 mg/dL and/or or an estimated glomerular filtration rate <40 mL/ min/1.73 m²

Exclusion criteria:

1) serum creatinine levels >8 mg/dL,

2) a history of dialysis,

3) multiple myeloma, 4) pulmonary edema,

4) acute myocardial infarction,

5) recent exposure to radiographic contrast within 2 days of the study,

6) pregnancy,

7) administration of theophylline, dopamine, mannitol, or fenoldopam

N total at baseline:

Intervention: 111

Control: 108

Important prognostic factors²:

For example

age ± SD:

I: 70 ± 9

C: 71 ± 9

Sex:

I: 88% M

C: 81% M

Groups comparable at baseline?

Yes

Describe intervention (treatment/procedure/test):

154 mEq/L sodium bicarbonate in dextrose and H2O,.

The initial intravenous bolus was 3 mL/kg/h for 1 hour immediately before contrast injection. After this, patients received the same fluid at a rate of 1 mL/kg/h during contrast exposure and for 6 hours after the procedure.

NAC orally at a dose of 1200 mg twice daily on the day before and the day of administration of the contrast agent (total of 2 days).

Describe control (treatment/procedure/test):

Isotonic saline (0.90%) was given intravenously at a rate of 1 mL/kg body weight per hour

(0.5 mL/kg for patients with left ventricular ejection fraction _40%) for 12 hours before and 12 hours after administration of the contrast agent.

NAC orally at a dose of 1200 mg twice daily on the day before and the day of administration of the contrast agent (total of 2 days).

Length of follow-up:

48 hours for laboratory parameters

5 days for clnical events

Loss-to-follow-up:

Intervention:

9/117 (8%)

8 had no follow-up sCr value

1 had no contrast exposure

Control:

7/118(6%)

7 had no follow-up sCr value

Incomplete outcome data:

As above

Outcome measures and effect size (include 95%CI and p-value if available):

CIN

(=increase _25% of creatinine concentration)

I: 2/108 (2%)

C: 11/111 (10%)

P=0.02

Renal failure requiring temporary dialysis:

I: 1/108 (1%)

C: 1/111 (1%)

p-value not reported

Authors’ conclusion:

The strategy of volume supplementation by sodium bicarbonate plus NAC seems to be superior to the combination of normal saline with NAC alone or with the addition of ascorbic acid in preventing CIN in patients at medium to high risk.

Castini, 2008

Type of study: randomized controlled trial

Setting: one hospital

Country: Italy

Source of funding: not reported

Inclusion criteria:

1) patients undergoing coronary angiography and/or percutaneous coronary intervention

2) aged 18 years or older with stable serum creatinine levels ≥1.2 mg/dL

Exclusion criteria:

1) serum creatinine levels >4 mg/dL,

2) a history of dialysis,

3) multiple myeloma,

4) pulmonary edema,

5) cardiogenic shock,

6) acute myocardial infarction,

7) emergency catheterization,

8) recent exposure to radiographic contrast media within 7 days of the study, 9) allergy to iodinate contrast media or NAC,

10) previous enrollment in the same or other protocols, 11) pregnancy,

12) administration of theophylline, mannitol, dopamine, dobutamine, nonsteroidal anti-inflammatory drugs, or fenoldopam.

N total at baseline:

Intervention: 52

Control: 51

Important prognostic factors²:

For example

age ± SD:

I: 70 ± 8

C: 73 ± 8

Sex:

I: 85% M

C: 84% M

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

154 mL of 1000 mEq/L SB added to 846 mL of 5% dextrose in H2O. The initial intravenous bolus was 3 mL/kg for 1 hour immediately before contrast injection. Thereafter, patients received the same fluid at a rate of 1 mL/kg per hour during contrast exposure and for 6 hours after the procedure.

Describe control (treatment/procedure/test):

saline (0.9%) given intravenously at a rate of 1 mL/kg body weight per hour for 12 hours before and 12 hours after administration of the contrast agent

Length of follow-up:

5 days

Loss-to-follow-up:

Not reported

Incomplete outcome data:

Not reported

Outcome measures and effect size (include 95%CI and p-value if available):

CIN1

(=an increase in serum creatinine concentration≥25% over the baseline value in any of the 3 predefined time-points: 24 hours, 48 hours and 5 days)

I: 7 (14%)

C: 7 (14%)

P>0.05

CIN2

(=the rate of an absolute increase in serum creatinine concentration ≥0.5 mg/dL at the same time-points)

I: 6 (12%)

C: 4 (8%)

p>0.05

No patients required dialysis.

Authors’ conclusion:

Our findings suggest that neither the addition of NAC nor the administration of SB add further benefit in CIN prevention, compared to standard hydration with isotonic saline infusion.

Hafiz, 2012

Type of study: randomized controlled trial

Setting: elective patients, two tertiary hospitals

Country: United states of america

Source of funding: not reported

Inclusion criteria:

1) patients undergoing elective coronary and peripheral angiography and intervention.

2) serum creatinine >1.6 mg/dl in non-diabetics and >1.4 mg/dl in diabetics or an estimated glomerular filtration rate (eGFR) of <50 ml/min/1.73 m2, calculated by the Modification of Diet in Renal Disease

(MDRD) formula

3) age >18 years

Exclusion criteria:

(1) were on dialysis; (2) had unstable renal function (defined as change in serum creatinine of

>0.4 mg/dl within 48 hr prior to the index procedure),

(3) had pulmonary edema,

(4) had serum bicarbonate level >34 mmol/L;

(5) received fenoldapam, mannitol, dopamine, or NAC within 48 hr prior to the index procedure;

(6) were in cardiogenic shock,

(7) were allergic to contrast media,

(8) were pregnant,

(9) were unable to provide informed consent.

N total at baseline:

Intervention: 159

Control: 161

Important prognostic factors²:

For example

age (IQR):

I: 74 (65-80)

C: 73 (63-80)

Sex:

I: 56% M

C: 57% M

eGFR
I: 42 (32-51)

C: 41 (33-50)

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

dextrose 5% in water containing 154 mEq/L of NaHCO3 with or without NAC

NAC was used in 50% of patients in both study arms in a similarly randomized fashion as above; 1,200 mg was administered orally 2–12 hr before the procedure followed by another 1,200 mg oral dose 6–12 hr after the procedure

Describe control (treatment/procedure/test):

intravenous 0.9% normal saline with or without NAC

NAC was used in 50% of patients in both study arms in a similarly randomized fashion as above; 1,200 mg was administered orally 2–12 hr before the procedure followed by another 1,200 mg oral dose 6–12 hr after the procedure

Length of follow-up:

48 hours

Loss-to-follow-up:

Not reported

Incomplete outcome data:

Not reported

Outcome measures and effect size (include 95%CI and p-value if available):

CI-AKI

(=increase in serum creatinine concentration of either >25% or >0.5 mg/dl at 48 hr after the procedure)

I: 12%

C: 9%

p>0.05

There were no deaths or major

adverse effects noted in our patient population during

the study period.

Authors’ coclusion:

Incidence of CI-AKI was no different in the NaHCO3 group compared to saline group, and NAC did not reduce CI-AKI in the two study arms.

Klima, 2012

Type of study: randomized controlled trial

Setting: elective patients, multi-center trial

Country: Switzerland

Source of funding: commercial and non-commerzial

Inclusion criteria:

All patients admitted with renal dysfunction {actual serum creatinine level above the upper limit of normal of the serum creatinine (0.93 mmol/L for women and .117 mmol/L for men) or estimated glomerular filtration rate (eGFR) ,60 mL/min/1.73 m2 [eGFR calculated using the abbreviated Modification of Diet in Renal Disease

(MDRD) study equation16]} scheduled to undergo an intra-arterial or intravenous radiographic contrast procedure on the next day

Exclusion criteria:

1) age ≥18 years,

2) pre-existing dialysis, allergy to radiographic contrast,

3) pregnancy,

4) severe heart failure (NYHA functional class III and IV),

5) N-acetylcysteine ≤24 h before contrast,

6) clinical condition requiring continuous fluid therapy, e.g. severe sepsis

N total at baseline:

Intervention: 87

Control: 89

Important prognostic factors²:

For example

age median (IQR):

I: 78 (70-82)

C: 75 (70-82)

Sex:

I: 66% M

C: 62% M

eGFR ± SD

I: 43 ± 11

C: 43 ± 12

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

The initial intravenous bolus was 3 mL/kg/h of 166 mEq/L sodium bicarbonate for 1 h immediately before radiocontrast injection. Following this, patients received the same fluid at a rate of 1 mL/kg/h during the contrast exposure and for 6 h after the procedure.

Describe control (treatment/procedure/test):

The infusion of 0.9% sodium chloride was administered at a continuous rate of 1 mL/kg/h, beginning from 8 p.m. on the day before the procedure and for at least 12h after the procedure.

Length of follow-up:

48 hours

Loss-to-follow-up:

Intervention:

6/93 (6%)

5 received no radiocontrast

1 refused participation

Control:

4/93 (4%)

4 received no radiocontrast

Incomplete outcome data:

As above

Outcome measures and effect size (include 95%CI and p-value if available):

CIN

(=an increase of ≥25% or an increase of ≥44 µmol/L in the baseline serum creatinine concentration within 48 h)

I: 9%

C:1%

P=0.02

No patient experienced a serious adverse event related to the infusion (death, intensive care unit admission). Also, no patient required intravenous diuretics or nitrates due to pulmonary congestion.

Authors’ conclusion:

Volume supplementation with 24 h sodium chloride 0.9% is superior to sodium bicarbonate for the prevention of

CIN.

Lee, 2011

Type of study: randomized controlled trial

Setting: elective patients, multicentre trial academic hospitals

Country: Korea

Source of funding: not reported

Inclusion criteria:

1) patients undergoing coronary or endovascular angiography or intervention

2) serum creatinine ≥1.1 mg/dl, estimated glomerular filtration rate (eGFR) ≤60 ml/min/1.73 m²,

3) age ≥18 years,

4) diagnosis with diabetes mellitus

Exclusion criteria:

1) inability to obtain informed consent,

2) serum creatinine ≥8 mg/dl, eGFR ≤15

ml/min/1.73 m² at rest,

end-stage renal disease on hemodialysis,

3) multiple myeloma,

4) pulmonary edema,

5) uncontrolled hypertension (systolic pressure >160 mm Hg or

diastolic pressure >100 mm Hg),

6) acute ST-segment elevation myocardial infarction while undergoing primary percutaneous intervention,

7) emergency coronary angioplasty or angiography,

8) use of contrast media within the previous 2 days,

9) pregnancy,

10) allergy to contrast medium

11) medications such as theophylline, dopamine, mannitol, fenoldopam, and NAC

N total at baseline:

Intervention: 193

Control: 189

Important prognostic factors²:

For example

age median (IQR)

I: 69 (63-73)

C: 68 (67-72)

Sex:

I: 70% M

C: 71% M

eGFR:
I: 46 (34-53)

C: 46 (37-53)

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

Sodium bicarbonate infusion (154 mEq/L in dextrose and water) was begun 1 hour before the start of contrast injection, starting at 3 ml/kg/hour and decreasing to 1 ml/ kg/hour during the procedure and for 6 hours after completion of the procedure

All patients received NAC 1,200 mg 2 times/day for 2 days starting the day before the index procedure

Describe control (treatment/procedure/test):

0.9% sodium chloride 1 ml/kg/hour for 12 hours before and after the procedure

All patients received NAC 1,200 mg 2 times/day for 2 days starting the day before the index procedure

Length of follow-up:

48 hours for laboratory parameters

6 months for clinical parameters

Loss-to-follow-up:

Intervention:

5/193 (3%)

All had no laboratory data

Control:

2/189 (1%)

All had no laboratory data

Incomplete outcome data:

As above

Outcome measures and effect size (include 95%CI and p-value if available):

CIN

(=a ≥25% increase in serum creatinine concentration

or a ≥0.5 mg/dl absolute increase in serum creatinine from baseline within 48 hours after contrast exposure)

I: 17 (9%)

C: 10 (5%)

P=0.17

Requirement of hemodialysis

I: 4 (2%)

C: 2 (1%)

P=0.69

Rates of death, myocardial infarction, and stroke did not differ significantly at 1 month and 6 months after contrast exposure.

Authors’ conclusion:

In conclusion, hydration with sodium bicarbonate is not superior to hydration with sodium chloride in preventing CIN in patients with diabetic nephropathy undergoing coronary or endovascular angiography or intervention.

Infusion rates were decreased to 0.5 ml/kg/hour in patients with left ventricular ejection fraction ≤45% in the 2 treatment arms.

Maioli, 2008

Type of study: randomized controlled trial

Setting: elective patients, one center

Country: Italy

Source of funding: not reported

Inclusion criteria:

1) patients with pre-angiographic estimated creatinin clearance <60 ml/min

2) undergoing planned angiographic procedures

Exclusion criteria:

1) creatinine clearance ≥ 60 ml/min n = 691

2) refusal to participate n = 18

3) administration of contrast medium within the previous 10 days n = 12

4) end stage renal disease n = 3

N total at baseline:

Intervention: 250

Control: 252

Important prognostic factors²:

For example

age median (IQR):

I: 74 (67-79)

C: 74 (70-79)

Sex:

I: 57% M

C: 61% M

eGFR ± SD:

I: 43 ± 11

C: 42 ± 10

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

Sodium bicarbonate (154 mEq/l in dextrose and water) received 3 ml/kg for 1 h before contrast medium, followed by an infusion of 1 ml/kg/h for 6 h after the procedure.

All patients received 600 mg oral NAC twice a day from the day before to the day after the procedure

Describe control (treatment/procedure/test):

1 ml/kg/h 0.9% sodium chloride for 12 h before and after the procedure

Length of follow-up:

5 days

Loss-to-follow-up:

Intervention:

4/252 (2%)

3 died

1 acute renal failure

Control:

5/250 (2%)

4 died

1 acute renal failure

Incomplete outcome data:

As above

Outcome measures and effect size (include 95%CI and p-value if available):

CIN

(=an absolute increase of at least 0.5 mg/dl over baseline serum creatinine within 5 days after the administration of the contrast medium)

I: 25 (10%)

C: 29 (12%)

P=0.60

CIN2

(=as a relative increase _25% over baseline serum creatinine within 5 days after contrast agent administration)

I: 15%

C: 21%

P=0.13

Death and acute renal failure, see column “Follow-up” for numbers, no significant difference in clinical events.

Authors’ conclusion:

Hydration with sodium bicarbonate plus NAC before contrast medium exposure is not more effective than hydration with isotonic saline plus NAC for prophylaxis of CIN in patients with moderate-to-severe renal dysfunction.

Nieto-Rios, 2014

Type of study: randomized controlled trial

Setting: elective patients, single center

Country: Colombia

Source of funding: not reported

Inclusion criteria:

1) Inpatients in a tertiary center, scheduled to undergo a procedure with the nonionic radiographic contrast agent iohexol.

2) serum creatinine levels of at least 1.2 mg/dL (106.1 μmol/L) and/or type 2 dia­betics,

Exclusion criteria:

1) current clinical diagnosis of exacerbated congestive heart failure, 2) ejection fraction <35% by previous echocardiography,

3) signs of acute pulmonary edema within 48 hours before the procedure,

4) systolic blood pressure <90 mmHg or requirement of vasopressors support,

5) patients with exposure to contrast 30 days prior to the study,

6) known allergy to contrast dye,

7) chronic renal disease with dialysis therapy,

8) criteria for dialytic urgency,

9) pregnancy,

10) requirement of an emergency procedure (e.g., aortography for diagnosis of aortic aneurism),

11) patients with serum potassium <3 mEq/L (because of the risk of hypokalemia induced by bicarbonate),

12) uncompensated diabetes mellitus (four different values >200 mg/dL in the previous 24 hours)

13) patient or physician refusal to participate.

N total at baseline:

Intervention: 107

Control: 113

Important prognostic factors²:

For example

age ± SD:

I: 61 ± 17

C: 60 ± 17

Sex:

I: 57% M

C: 58% M

Baseline sCr (mg/dL):

I: 1.3 ± 0.3

C: 1.3 ± 0.3

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

3 ml/kg of sodium bicarbonate solution (150 mEq/L) one hour prior to procedure and then drip rate was decreased to 1 ml/ kg/hour until 6 hours post procedure

Describe control (treatment/procedure/test):

1 ml/ kg/hour of normal saline solution, starting 12 hours before and continuing 12 hours after iohexol contrast

Length of follow-up:

5 days

Loss-to-follow-up:

Intervention:

7/107 (7%)

3 died

1 withdrawed

3 technical difficulties

Control:

1/113 (1%)

1 died

Incomplete outcome data:

As above

Outcome measures and effect size (include 95%CI and p-value if available):

CIN

(= increase in serum creatinine on 25% or more within 2 days after administration of radiographic con­trast)

I: 12 (12%)

C: 8 (7%)

RR: 1.68, 95% CI: 0.72 – 3.94

p>0.05

Decompensated heart failure

I: 3 (3%)

C: 7 (6%)

P=0.34

Authors conclusion:

Our investigation showed that there were no differences between normal saline solution (extended infusion) vs. bicarbonate solution for nephroprotection.

Shavit, 2009

Type of study: randomized controlled trial

Setting: elective patiens, single-center

Country: Israel

Source of funding: not reported

Inclusion criteria:

1) patients with chronic kidney disease (CKD) stage III–IV undergoing cardiac catheterization

Exclusion criteria:

1) plasma creatinine levels more than

8 mg/dL or eGFR less than 15 mL/min, change in plasma creatinine levels of ≥0.5 mg/dL during the previous 24 hours,

2) preexisting dialysis, multiple myeloma,

3) pulmonary edema,

4) uncontrolled hypertension (systolic

>160 mmHg, diastolic >100 mmHg),

5) recent exposure to radiographic contrast, or other nephrotoxic medications (within 2 days of the study),

6) allergy to radiocontrast,

7) pregnancy

N total at baseline:

Intervention: 51

Control: 36

Important prognostic factors²:

For example

age ± SD:

I: 72 ± 10

C: 71 ± 9

Sex:

I: 84% M

C: 70% M

eGFR (ml/min/1.73m²) ± SD:

I: 43 ± 11

C: 40 ± 10

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

154 mEq/L sodium bicarbonate in 5% dextrose in water mixed by adding 154 mL of 1,000 mEq/L sodium bicarbonate to 846 mL of 5% dextrose in water. The initial IV bolus was 3 mL/kg for 1 hour before cardiac catheterization. Following this bolus, patients received the same fluid at a rate of 1 mL/kg per hour during the contrast exposure and for 6 hours after the procedure.

For patients weighing more than 110 kg, the initial fluid bolus and drip were limited to those doses administered to patients weighing

110 kg.

Describe control (treatment/procedure/test):

12-hour infusion of 154 mEq/L (0.9%) sodium chloride at a rate of 1 mL/kg per hour before cardiac catheterization and NAC 600 mg × 2/d

orally the day before and the day of the procedure

Length of follow-up:

2 days

Loss-to-follow-up:

Intervention:

0 (0%)

Control:

5/41 (12%)

No laboratory evaluation at baseline or after contrast exposure

Incomplete outcome data:

As above

Outcome measures and effect size (include 95%CI and p-value if available):

CI-AKI
(=an increase of 25% or 0.3 mg/dL or more in plasma creatinine within

2 days of contrast administration)

I: 5/51 (10%)

C: 3/36 (8%)

p>0.05

CI-AKI2

(=an increase in plasma creatinine of 0.3 mg/dL or more from baseline)
I: 17%

C: 16%

P>0.05

No patient developed more than 50% increment of creatinine or required renal replacement therapy during the hospitalization.

Authors’ conclusion:

Hydration with sodium bicarbonate is not more effective than hydration with sodium chloride and oral NAC for prophylaxis of CI-AKI in patients with CKD stage III–IV undergoing cardiac catheterization.

Sodium bicarbonate versus saline: “other schedules” for coronary angiography and/or percutaneous intervention

Chong, 2015

Type of study: randomized controlled trial

Setting:

University Heart Centre

Country: Singapore

Source of funding: not reported

Inclusion criteria:

1) adults >21 years of age;

2) glomerular filtration

rate (GFR) of 15–60 mL/min/1.73m2 – calculated by the abbreviated Modification

of Diet in Renal Disease (MDRD) formula –

3) scheduled to undergo elective cardiac

catheterisation with or without PCI

4) were able to receive pre-hydration for 12 h.

Exclusion criteria:

1) end-stage renal failure with GFR of b15 mL/min/1.73 m2,

acute renal failure with a N44 μmol/L increase in serum Cr levels in the previous 24 h;

2) pre-existing dialysis;

3) pulmonary oedema or moderate to severe congestive heart failure

(New York Heart Association III–IV);

4) inability to withstand the fluid load;

5) presence

of haemodynamic compromise, uncontrolled hypertension (untreated systolic blood pressure

N160mmHg, or diastolic blood pressure N100mmHg)

6) emergency cardiac catheterisation

7) exposure to

contrast in the previous two days;

8) allergies to contrast or NAC;

9) administration of sodium bicarbonate or NAC within 48 h of cardiac catheterisation;

10) clinical conditions requiring

continuous fluid therapy such as severe sepsis;

11) Use of potentially renal-toxic drugs;

12) cisplatin within 48 h of cardiac catheterisation and throughout the study

duration;

Important prognostic factors²:

For example

age ± SD:

I: 69 ± 10

I2: 71 ± 10

C: 67 ± 10

Sex:

I1: 72% M

I2: 78% M

C: 78% M

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

I1: High-dose oral NAC with a sustained intravenous sodium chloride infusion (NAC group)

I2: Intravenous sodium bicarbonate infusion (SOB

group)

Describe control (treatment/procedure/test):

C1: Oral NAC and abbreviated intravenous sodium bicarbonate infusion (COM group)

Length of follow-up:

48 hrs

Loss-to-follow-up:

I1: 28/185

I2: 29/182

C1: 25/181

Death:

I1: 0/185

I2: 1/182

C1: 2/181

Outcome measures and effect size (include 95%CI and p-value if available):

CIN, which was defined as ≥25% increase of serum Cr concentration

or a ≥44 μmol/L (0.5mg/dL) increase in serum Cr within 48 h of cardiac catheterisation

or PCI

I1: 6.5%

I2: 12.8%

C1: 10.6%

P=0.214

Authors’ conclusion

‘The combination regimenwas not superior to individual regimens in preventing CIN in patientswith

baseline renal impairment. There was a trend suggesting that the 12-hour sustained sodium chloride prehydration

regimen was more protective than the 1-hour abbreviated SOB regimen.’

Motohiro, 2011

Type of study: randomized controlled trial

Setting: elective patient, 2 hospitals

Country: Japan

Source of funding: not reported

Inclusion criteria:

1) patients undergoing coronary angiography or intervention

2) ≥20 years old

3) had an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m²

Exclusion criteria:

1) serum creatinine levels >4 mg/dl,

2) changes in serum creatinine levels of ≥0.5 mg/dl during the previous 24 hours,

3) pre-existing dialysis,

4) pulmonary edema,

5) uncontrolled hypertension (treated systolic blood pressure >160 mm Hg or diastolic blood pressure >100 mm Hg),

6) emergency catheterization,

7) exposure to radiographic contrast within previous

2 days,

8) any allergy to radiographic contrast medium

N total at baseline:

Intervention: 77

Control: 78

Important prognostic factors²:

For example

age ± SD:

I: 74 ± 7

C: 71 ± 9

Sex:

I: 64% M

C: 76% M

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

0.9% sodium chloride for 12 hours before and after the procedure.

Sodium bicarbonate solution was prepared by adding 154 ml of sodium bicarbonate 1,000 mEq/L to

846 ml of 5% dextrose in water. In the sodium bicarbonate group the sodium bicarbonate solution was changed 3 hours before contrast administration

Describe control (treatment/procedure/test):

0.9% sodium chloride for 12 hours before and after the procedure.

Length of follow-up:

1 months

Loss-to-follow-up:

Intervention:

2/79 (2%)

No laboratory test results

Control:

1/79 (1%)

 Angialgia due to sodium bicarbonate infusion

Incomplete outcome data:

As above

Outcome measures and effect size (include 95%CI and p-value if available):

CIN

(=25% increase or an absolute increase of

_0.5 mg/dl in serum creatinine from baseline value, which appeared within 2 days of the produce)

I: 2 (3%)
C: 10 (13%)

P=0.02

relative risk 0.176, 95% confidence interval

0.037 to 0.83

No patient required

Hemodialysis.

Authors’ conclusion

Sodium chloride plus sodium bicarbonate is more effective than sodium chloride alone for prophylaxis of CIN and can lead to retention of better long-term renal function.

Tamura, 2009

Type of study: randomized controlled trial

Setting: elective patients, two hospitals

Country: Japan

Source of funding: not reported

Inclusion criteria:

1) Patients who were scheduled for elective coronary arteriography or percutaneous coronary intervention

2) age >20 years

3) serum creatinine (Cr) level >1.1 to <2.0 mg/dl.

Exclusion criteria:

1) allergy to contrast medium, pregnancy,

2) history of dialysis,

3) exposure to contrast-medium within the preceding 48 hours of the study,

4) acute coronary syndrome within the preceding 1 month of the study,

5) severe symptoms of heart failure (New York Heart Association functional class IV),

6) left ventricular ejection fraction >25%,

7) severe chronic respiratory disease,

8) single functioning kidney,

9) administration of N-acetylcysteine, theophylline, dopamine, or mannitol

N total at baseline:

Intervention: 72

Control: 72

Important prognostic factors²:

For example

age ± SD:

I: 73 ± 8

C: 72 ± 10

Sex:

I: 83% M

C: 92% M

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

Standard hydration with sodium chloride plus single-bolus intravenous administration of sodium bicarbonate (20 ml /20 mEq; Meyron 84, Otsuka Pharmaceutical,

Inc., Tokyo, Japan) 5 minutes before contrast exposure

Describe control (treatment/procedure/test):

Standard hydration with sodium chloride alone

(=intravenous administration with isotonic saline (0.9%) at a rate of 1 ml/kg/hour (0.5 ml/kg/hour for patients with left ventricular ejection fraction <40%) for 12 hours before and 12 hours after an elective coronary procedure. For patients weighing >80 kg, infusion rate was limited to 80 ml/hour (40 ml/hour for patients with left ventricular ejection fraction _40%).

Length of follow-up:

3 days

Loss-to-follow-up:

All patients completed the study

Incomplete outcome data:

All patients completed the study

Outcome measures and effect size (include 95%CI and p-value if available):

CIN

(=an increase ≥25% or ≥0.5 mg/dl in serum Cr within the first 3 days after the procedure compared to baseline value)

I: 1.4%

C: 12.5%

P=0.017

Adverse clinical events (acute pulmonary edema, acute renal failure requiring dialysis, and death within 7 days of procedure)

I: 0%

C: 1.4%

p>0.05

Authors’ conclusion

In conclusion, single-bolus intravenous administration of sodium bicarbonate in addition to standard hydration can more effectively prevent CIN than standard hydration alone in patients with mild renal insufficiency undergoing an elective coronary procedure.

Turedi, 2016

Type of study: randomized controlled trial

Setting: academic emergency center

Country: Turkey

Source of funding: not reported

Inclusion criteria:

1) Undergoing contrastenhanced

thoracic CT due to suspected PE;

2) aged over

18 years;

3) with measure-able basal creatinine levels pretomography

and;

4) measureable serum creatinine levels 48– 72 hours posttomography, and with one or more of the

risk factors for CIN. The risk

factors were preexisting renal dysfunction (Cr 1.4 mg/dL or a high or calculated glomerular filtration rate

[GFR] < 60 mL/min/1.73 m²), diabetes mellitus, hypertension

receiving treatment, hypotension (systolic blood

pressure < 90 mm Hg), coronary artery disease, history of  nephrotoxic drug use (nonsteroidal anti-inflammatory

drugs, cisplatin, aminoglycoside, amphotericin B), liver disease, congestive heart failure (active or history thereof), age 75 or over, and anemia (hematocrit

< 30%).

Exclusion criteria:

1) end-stage renal disease already in

peritoneal dialysis;

2) hemodialysis;

3) pregnant women;

4) subjects with a known allergy to NAC or NaHCO3;

5) patients requiring NAC therapy or NaHCO3 therapy

for existing additional disease;

6) exposed to contrast

material for any reason in the previous 10 days or 7) during the in-hospital follow-up period

8) patients

who refused to participate

Important prognostic factors²:

For example

age ± SD:

I: 76 (72-80)

I2: 77 (71-80)

C: 74 (73-76)

Sex:

I1: 48% M

I2: 51% M

C: 53% M

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

I1: 3 mL/kg intavenous NAC+NS solution (3 g NAC was made up to 1000 mL with NS),

I2: NaHCO3 + NS solution (132 mEq NaHCO3 was made up to

1000 mL with NS)

Describe control (treatment/procedure/test):

C1: NS alone 1 hour before CTPA and 1 mL/kg intavenous per hour for a minimum of 6 hour after CTPA.

Length of follow-up:

48-72 hrs

Loss-to-follow-up:

I1: 7/85

I2: 8/85

C1: 11/87

Death:

I1: 4/85

I2: 2/85

C1: 6/87

Outcome measures and effect size (include 95%CI and p-value if available):

CIN development creatinine levels and post-CTPA creatinine

levels measured 48–72 hours following contrast exposure

and an increase ≥25% or 0.5 mg/dL

I1: 23.5%

I2: 21.2%

C1: 26.4%

P=0.719

Authors’ conclusion

‘In conclusion, there were no statistically significant differences observed

among prophylactic NAC, NaHCO3, and NS in prevention of CIN following contrast-enhanced CTPA.’

Ueda, 2011

Type of study: randomized controlled trial

Setting: emergency patients, single center

Country: Japan

Source of funding: not reported

Inclusion criteria:

1) patients undergoing an emergent (within 60 minutes of admission) diagnostic or interventional coronary procedure, such as coronary angiography or percutaneous coronary intervention

2) >20 years old

3) had renal insufficiency, defined by a serum creatinine

(Cr) concentration of >1.1 mg/dl or estimated glomerual filtration rate (eGFR) of <60 ml/min

Exclusion criteria:

1) change in the serum Cr concentration of >0.5 mg/dl during the 24 hours before the procedure,

2) pre-existing dialysis, exposure to the contrast media within 2 days before the study,

3) allergy to the contrast media, pregnancy,

4) previous or planned administration of mannitol, fenoldopam, N-acetylcysteine, theophylline, dopamine, or nonstudy sodium bicarbonate

N total at baseline:

Intervention: 30

Control: 29

Important prognostic factors²:

For example

age ± SD:

I: 77 ± 9

C: 75 ± 10

Sex:

I: 79% M

C: 77% M

sCr (mg/dL) ± SD:

I: 1.32 ± 0.46

C: 1.51 ± 0.59

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

Intravenous bolus injection of 154 mEq/L of sodium bicarbonate at a dose of 0.5 ml/kg, as soon as possible after they were admitted, before the administration of the contrast medium

Intravenous infusion of 154 mEq/L sodium bicarbonate at 1 ml/kg/hour during and for 6 hours after the coronary procedure

Describe control (treatment/procedure/test):

Intravenous bolus injection of 154 mEq/L of sodium chloride at a dose of 0.5 ml/kg, as soon as possible after they were admitted, before the administration of the contrast medium

Intravenous infusion of 154 mEq/L sodium bicarbonate at 1 ml/kg/hour during and for 6 hours after the coronary procedure

Length of follow-up:

2 days

Loss-to-follow-up:

Intervention:

0 (0%)

Control:

1/30 (3%)

Circulatory failure

Incomplete outcome data:

As above

Outcome measures and effect size (include 95%CI and p-value if available):

CIN

(=an increase by >25% or >0.5 mg/dl of the serum creatinine level within 2 days after the procedure)

I: 1 (3%)

C: 8 (28%)

RR: 0.12, 95% CI: 0.016 – 0.91

P=0.01

Congestive heart failure

I: 5/30 (17%)

C: 6/29 (21%)

p>0.05

Death

I: 2/30 (7%)

C: 2/29 (7%)

p>0.05

No patients developed acute renal failure requiring hemodialysis.

Authors’ conclusion

In conclusion, rapid alkalization by bolus injection of sodium bicarbonate was effective for the prevention of CIN in patients with CKD undergoing emergent procedures.

Sodium bicarbonate short schedule versus saline long schedule for computed tomography

Kooiman, 2014

Type of study: randomized controlled trial

Setting: elective patients, multi-center trial

Country: the Netherlands

Source of funding: non-commercial

Inclusion criteria:

1) In- and outpatients electively scheduled for CE-CT regardless of the indication

2) least 18 years of age, had CKD (eGFR <60 mL/min/1.73 m² estimated by the Modification of Diet in Renal Disease formula

3) eligible for the fluid challenge of saline hydration

Exclusion criteria:

1) pregnancy,

2) previous contrast administration within the last 7 days,

3) documented allergy for iodinated contrast media,

4) haemodynamic instability (systolic blood

pressure <100 mmHg)

5) previous participation in the trial

N total at baseline:

Intervention: 267

Control: 281

Important prognostic factors²:

For example

age ± SD:

I: 72 ± 10

C: 73 ± 10

Sex:

I: 60% M

C: 61% M

Mean eGFR:

I: 50 ± 13

C: 51 ± 14

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

250 mL intravenous 1.4% sodium bicarbonate 1 h prior to CE-CT without hydration post-CE-CT

Describe control (treatment/procedure/test):

2000 mL of intravenous 0.9% saline, 1000 mL prior to and 1000 mL post-CE-CT

Length of follow-up:

96 hours

Loss-to-follow-up:

Intervention:

15/267(6%)

2 treated according to protocol

5 CT without iv contrast

6 CT cancelled and no hydration

Control:

20/281 (7%)

7 treated according to protocol

7 CT cancelled and no hydration

4 CT without iv contrast

2 treated with sodium bicarbonate

Incomplete outcome data:

As above

Outcome measures and effect size (include 95%CI and p-value if available):

CI-AKI

(=serum creatinine increase >25%/>44 μmol/L (0.5 mg/dL)

I: 8 (3%)

C: 14 (5%)

P=0.23

Recovery of kidney function:

I: 75%

C: 69%

P=0.81

Acute heart failure due to volume expansion (based on the

treating physician’s clinical judgement) occurred in none of the patients in the sodium bicarbonate group versus 6 of 281 patients in the saline group (P = 0.03)

None of the CI-AKI patients developed

a need for dialysis.

Authors’ conclusion

Short hydration with sodium bicarbonate prior to CE-CT was non-inferior to peri-procedural saline hydration with respect to renal safety and may result in healthcare savings.

Controlled diuresis for coronary angiography and/or percutaneous intervention

Barbanti, 2016

Type of study: randomized controlled trial

Setting: university hospital

Country: Italy

Source of funding: not reported

Inclusion criteria:

1) All patients with

symptomatic severe aortic stenosis undergoing TAVI

were considered eligible

Exclusion criteria:

1) chronic end-stage renal failure on dialysis;

2) episode of acute congestive heart failure with left

ventricular ejection fraction <30% in the past 30 days

before randomization;

3) contraindica-tions to placement

of a Foley catheter;

4) urgent TAVI

5) unavailability of

the RenalGuard system.

Important prognostic factors²:

For example

age ± SD:

I: 82 (78-83)

C: 81 (78-84)

Sex:

I: 61% F

C: 59% F

Serum creatine ± SD

I: 1.0 (0.85-1.15)

C: 0.97 (0.83-1.16)

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

RenalGuard therapy received hydration with a normal saline solution; with an initial bolus (priming) of 250 ml was infused over 30 min (preprocedural. Urine flow was monitored and

maintained at the target value throughout the procedure

and during the following 4 h.

phase).

Describe control (treatment/procedure/test):

control group received

sodium normal saline solution at a rate of 1 ml/kg/h

12 h before TAVR, during contrast exposure, and for 6 h after the procedure.

Length of follow-up:

78 hrs

Loss-to-follow-up:

No loss to follow-up

Outcome measures and effect size (include 95%CI and p-value if available):

AKI

(defined: absolute reduction in kidney

function (<72 h) and defined as: 1) stage 1: increase in

serum creatinine to 150% to 200% (1.5 to 2.0x increase

compared with baseline) or increase of >0.3

mg/dl (≥26.4 mmol/l); 2) stage 2: increase in serum

creatinine to 200% to 300% (2.0 to 3.0x increase

compared with baseline); and 3) stage 3: increase in

serum creatinine to ≥300% (>3_ increase compared

with baseline) or serum creatinine of ≥4.0 mg/dl

(≥354 mmol/l) with an acute increase of at least 0.5

mg/dl (44 mmol/l).)

I: 4 (5.4%)

C: 13 (25.2%)

RR: 0.21, 95% CI: 0.06 – 0.71

P=0.014

Cardiovascular death

I: 0/56(0%)

C: 1/56 (1.8%)

P=0.306

Death

I: 1/56 (1.8%)

C: 2/56 (3.6%)

P=0.537

Authors’ conclusion

‘In summary, furosemide-induced diuresis with matched isotonic intravenous hydration using the RenalGuard system

is an effective therapeutic tool to reduce the occurrence of AKI in patients undergoing TAVR.’

Brar, 2014

Type of study: randomized controlled trial

Setting: elective patients, 1 center

Country: United states of America

Source of funding: not reported

Inclusion criteria:

1) patients referred to the cardiac catheterisation laboratory

2) an estimated glomerular fi ltration rate (GFR) of 60 mL/min per 1・73 m² or lower;

3) age 18 years or older;

4) at least one of the following: diabetes mellitus, history of congestive heart failure, hypertension (blood pressure >140/90 mm Hg or treatment with antihypertensive medication), or age older than 75 years.

Exclusion criteria:

1) inability to obtain consent from participants,

2) emergency cardiac catheterisation (eg, primary percutaneous coronary intervention for ST-segment elevation myocardial infarction),

3) renal replacement therapy,

4) exposure to radiographic contrast media within the previous 2 days,

5) allergy to radiographic contrast media,

6) acute decompensated heart failure,

7) severe valvular heart disease,

8) mechanical aortic prosthesis,

9) left ventricular thrombus,

10) history of kidney or heart transplantation,

11) change in estimated GFR of 7.5% or more per day or a cumulative change of 15% or more during the pre ceding 2 or more days.

N total at baseline:

Intervention: 196

Control: 200

Important prognostic factors²:

For example

age ± SD:

I: 71 ± 9

C: 72 ± 8

Sex:

I: 64% M

C: 59% M

eGFR ± SD

I: 48 ± 9

C: 48 ± 9

Groups comparable at baseline?

Describe intervention (treatment/procedure/test):

0.9% sodium chloride bolus infusion at

3 mL/kg for 1 h

The fl uid rate was adjusted according to the left ventricular end-diastolic pressure as follows: 5 mL/kg/h for left ventricular end-diastolic pressure lower than 13 mmHg,

3 mL/kg/h for pressure of 13–18 mmHg, and

1.5 mL/kg/h for pressure higher than 18 mmHg. The fl uid rate was set at the start of the procedure (before contrast exposure), continued for the duration of the procedure, and for 4 h post-procedure.

Describe control (treatment/procedure/test):

0.9% sodium chloride bolus infusion at

3 mL/kg for 1 h

5 mL/kg per h.

The fl uid rate was set at the start of the procedure (before contrast exposure), continued for the duration of the procedure, and for 4 h post-procedure.

Length of follow-up:

2-8 weeks for laboratory parameters

6 months for clinical events

Loss-to-follow-up:

Intervention:

0 (0%)

Control:

0 (0%)

Incomplete outcome data:

Intervention:

18/196 (9%)

12 had 1 sCr value

6 had no sCr value

Control:

28/200 (14%)

24 had 1 sCr value

4 had no sCr value

Outcome measures and effect size (include 95%CI and p-value if available):

CIN

(=a greater than 25% or 0.5 mg/dL increase in the serum creatinine concentration)

I: 12/178 (7%)

C: 28/172 (16%)

RR: 0.41, 95% CI: 0.22 – 0.79, p=0.005

6-months mortality

I: 0.5%

C: 4%

P=0.037

No significant difference in other adverse clinical events at 30 days or 6 months

In total, six patients (1・5%)—three in each group— terminated the intravenous fl uids early, the reason for which was shortness of breath in all six patients.

Authors’ conclusion:

Left ventricular end-diastolic pressure-guided fl uid administration seems to be safe and eff ective in preventing contrast-induced acute kidney injury in patients undergoing cardiac catheterisation.

Briguori, 2011

Type of study: randomized controlled trial

Setting: elective patients, multicenter

Country: Italy

Source of funding: not reported

Inclusion criteria:

1) patients with chronic kidney disease scheduled for coronary and/or peripheral angiography and/or angioplasty with an estimated glomerular filtration rate (eGFR) ≤30mL /min/ 1.73 m² and/or a risk score ≥11)

Exclusion criteria:

1) acute myocardial infarction;

2) acute pulmonary edema;

3) cardiogenic shock;

4) dialysis;

5) multiple myeloma;

6) administration of sodium bicarbonate, theophilline, dopamine, mannitol,

and/or fenoldopam;

7) recent (<48 hours) administration of iodinated contrast medium

8) enrollement in another study

N total at baseline:

Intervention: 146

Control: 146

Important prognostic factors²:

For example

age ± SD:

I: 76 ± 8

C: 75 ± 9

Sex:

I: 61% M

C: 71% M

eGFR ± SD:

I: 32 ± 7

C: 32 ± 9

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

hydration with normal saline plus NAC controlled by the RenalGuard system

NAC was administered only iv (1500 mg in 1L saline) during the 3 phases (preprocedural,

intraprocedural, and postprocedural) of the RenalGuard therapy.

Describe control (treatment/procedure/test):

154 mEq/L sodium bicarbonate in dextrose and H2O.

The initial intravenous bolus was 3 mL/kg per hour for at least 1 hour before contrast injection. Then, all patients received the same fluid at a rate of 1 mL/kg per hour during contrast exposure and for 6 hours after the procedure.

NAC orally at a dose of 1200 mg twice daily the day before and the day of administration of the contrast agent (for a total of 2 days)

additional NAC dose (1200 mg diluted in 100 mL normal

saline) was administered intravenously during the procedure.

The total NAC dose was 6 g.

Length of follow-up:

1 week

Loss-to-follow-up:

0 (0%) in both groups

Incomplete outcome data:

Intervention:

0 (0%)

Control:

3/147 (2%)

2 discontinued treatment

1 did not receive allocated treatment

Outcome measures and effect size (include 95%CI and p-value if available):

CI-AKI

(=an increase in sCr concentration ≥0.3 mg/dL above the baseline value at 48 hours after administration of Contrast or the need fordialysis)
I: 16/146 (11%)

C: 30/146 (21%)

Odds ratio: 0.47, 95% CI 0.24 – 0.92

P<0.05

Authors’ conclusion:

RenalGuard therapy is superior to sodium bicarbonate and N-acetylcysteine in preventing contrast-induced acute kidney injury in high-risk patients.

The risk score for predicting CI-AKI was calculated according to the following algorithm: hypotension (integer score 5), intra-aortic balloon pump support (integer score 5), congestive heart failure (integer score 4), age >75 years (integer

score 4), diabetes mellitus (integer score 3), eGFR _60

mL/min/1.73 m² (integer score 2 to 6), preexisting anemia(integer score 3), and CM volume (integer score 1 for each 100 cm³).

The global scores ≥5, 6 to 10, 11 to 16, and _16 predict a CI-AKI risk of 7.5%, 14%, 26.1%, and 57.3%, respectively.

Marenzi, 2012

Type of study: randomised controlled trial

Setting: elective and emergency patients

Country: Italy

Source of funding: not reported

Inclusion criteria:

1) age ≥18 years and ≤85 years, and elective or urgent (within 24 h from hospital admission because of non–ST-segment elevation [acute] myocardial infarction [NSTEMI]) coronary angiography and, when indicated, percutaneous coronary intervention (PCI).

Exclusion criteria:

1) primary or rescue PCI and angiography procedures requiring a direct renal injection of contrast,

2) cardiogenic shock, overt congestive heart failure,

3) acute respiratory insufficiency,

4) recent acute kidney injury,

5) chronic peritoneal

or hemodialysis treatment,

6) known furosemide hypersensitivity,

7) receipt of intravenous contrast within 10 days before the procedure or another planned contrast-enhanced procedure in the following 72 h,

8) contraindications to placement of a Foley catheter in the bladder.

N total at baseline:

Intervention: 87

Control: 83

Important prognostic factors²:

For example

age ± SD:

I: 73 ± 7

C: 74 ± 8

Sex:

I: 78% M

C: 78% M

eGFR ± SD:
I: 1.8 ± 0.6

C: 1.7 ± 0.5

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

Approximately 90 min before the coronary procedure, Furosemide with matched hydration treatment was started with an initial intravenous bolus (250 ml) of normal saline solution over 30 min.

Furosemide was then administered as a single intravenous bolus of 0.5 mg/kg (up to a maximum of 50 mg).

Urine output was calculated continuously by the system, and when a urine output rate >300 ml/h was achieved, patients were brought to the catheterization laboratory and underwent coronary angiography. Matched hydration was continued throughout the catheterization procedure and for 4 h after the last contrast dose. At this time, therapy was discontinued.

Additional doses of furosemide (up to a maximal cumulative dose of 2.0 mg/kg) were given in cases where the urine output was below 300 ml/h during treatment. The Foley catheter was removed 24 h after the procedure.

Describe control (treatment/procedure/test):

continuous intravenous infusion of isotonic saline at a rate of 1 ml/kg/h (0.5ml/kg/h in case of left ventricular ejection fraction ≤40%) for at least 12 h before and 12 h after the procedure.

Length of follow-up:

72 hours

Loss-to-follow-up:

Intervention:

2/89 (2%)

Failed to insert foley catheter

Control:

2/85 (2%)

Withdrawal of treatment due to pulmonary edema

Incomplete outcome data:

As described above)

Outcome measures and effect size (include 95%CI and p-value if available):

CIN

(=a ≥25% or ≥0.5 mg/dl rise in serum creatinine over baseline during the first 72 h post-procedure)

I: 4 (5%)

C: 15 (18%)

P=0.005

Cumulative in-hospital complications

I: 8%

C: 18%

P=0.052

Authors’ conclusion:

In patients with CKD undergoing coronary procedures, furosemide-induced high urine output with matched hydration significantly reduces the risk of CIN and may be associated with improved in-hospital outcome.

Qian, 2016

Type of study: randomised controlled trial

Setting: elective patients, multiple centers

Country: Japan

Source of funding: not reported

Inclusion criteria:

1) patients with CKD and chronic heart failure undergoing coronary procedures

Exclusion criteria:

-

N total at baseline:

Intervention: 132

Control: 132

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

Central-venous pressure guided hydration group

Describe control (treatment/procedure/test):

Standard hydration group

Length of follow-up:

48 hours

Loss-to-follow-up:

Not reported

Incomplete outcome data:

Not reported

Outcome measures and effect size (include 95%CI and p-value if available):

CIN

(=an increase by >25% or >0.5 mg/dl of the serum creatinine level within 2 days after the procedure)

I: 16%

C: 30%

P=0.006

Acute heart failure:

I: 3.8%

C: 3.0%

P=0.50

Authors’ conclusion:

Controlled vnous pressure guided fluid administration can safely and effectively reduce the risk of CIN in patients with CKD and chronic heart failure.

Usmiani, 2015

Type of study: randomized controlled trial

Setting: elective patients

Country: Brazil

Source of funding: not reported

Inclusion criteria:

1) patients with chronic kidney disease (CKD) undergoing coronary

procedures

Exclusion criteria:

-

N total at baseline:

Intervention: 65

Control: 68

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

iv 250 mL isotonic saline bolus, followed by a 0.5 mg/kg furosemide i.v. bolus to forced diuresis. A dedicated device automatically matched the isotonic saline i.v. infusion rate to the urinary output for 1 h before, during and 4 h after the procedure.

Describe control (treatment/procedure/test):

Standard saline and bicarbonate hydration

Length of follow-up:

2 days

Loss-to-follow-up:

Not reported

Incomplete outcome data:

Not reported

Outcome measures and effect size (include 95%CI and p-value if available):

CI-AKI

(=an increase by >25% or >0.5 mg/dl of the serum creatinine level within 2 days after the procedure)

I: 7%

C: 25%

P=0.01

Major adverse cardiovascular events

I: 7%

C: 32%

P<0.01

Authors’ conclusion:

In patients with CKD undergoing coronary procedures, furosemide-induced high urine output with matched hydration significantly reduces the risk of CIN and may be associated with improved in-hospital outcome.

Usmiani, 2016

Type of study: randomized controlled trial

Setting: university hospital

Country: Italy

Source of funding: not reported

Inclusion criteria:

1) Elgibile for voth procedures 2) eGFR of less than 60 mL/

min/1.73m2

Exclusion criteria:

1) primary PCI (emergency

procedure);

2) cardiogenic shock;

3) acute heart failure;

4) endstage

renal disease on haemodialysis;

5) urinary tract infections

within the last 3 months;

6) benign prostatic hyperplasia

and;

7) previously known difficulties in urinary

catheterization.

Important prognostic factors²:

For example

age ± SD:

I1: 76 ± 9

C: 75 ± 8

Sex:

I1: 22% F

C: 29% F

Serum creatine ± SD

I1: 1.54 ±0.43

C: 1.42 ±0.41

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

Matched hydration was to be performed with the Renal-

Guard System.

250 mL i.v. isotonic saline

bolus is given in 30 min, followed by 0.5 mg/kg i.v. furosemide to forced diuresis. Isotonic saline i.v. infusion proceeds automatically, rate-matched with diuresis

Describe control (treatment/procedure/test):

BS-NAC intravenous hydration (isotonic saline/

N-acetylcysteine/vitamin C)

1000 mL isotonic saline i.v. administration 12 h before

procedure (rate-adjusted according to LVEF 20–40mL/h if LVEF<30%, 80–120 mL/h if LVEF 30–50%, 200 mL/h if LVEF >50%).

Plus 3 mL/kg/h 1.4% SB solution i.v. infusion for 1 h before

Plus: 5000mg p.o. Vitamin C

Plus: 1200mg p.o. N-acetylcysteine

Length of follow-up:

7 days

Loss-to-follow-up:

9 loss to follow-up

I: 8/67

C: 1/66

Outcome measures and effect size (include 95%CI and p-value if available):

AKI

(CIAKI after

coronary angiography/PCI as defined by an increase of sCr +0.3 mg/dL in 48 h or +50% in 7 days)

I: 4 (6%)

C: 16 (24%)

P=0.01

Cardiovascular death

I: 1/59(1.7%)

C: 7/65 (10.8%)

Authors’ conclusion

‘Matched hydration was more effective than BS-NAC

in CIAKI prevention.’