Preventing radiocontrast-induced nephropathy in chronic kidney disease patients undergoing coronary angiography

Table 1 Risk factors for radiocontrast-induced nephropathy

Modifiable risk factors

Higher dose of contrast agent used

Congestive heart failure

Periprocedural shock

Anemia or postprocedural drop in hematocrit

Use of nephrotoxins

Use of nonsteroidal anti-inflammatory medications

Dehydration

Hypertension or blood pressure control

Diabetes mellitus or sugar control

Increased CK-MB

Urgent or emergency priority of the procedure

Need for cardiac surgery after contrast exposure

Preprocedural intra-aortic balloon pump use

Non-modifiable risk factors

Age > 75 yr

Female sex

Baseline renal function

Table 2 Clinical trials comparing prophylactic renal replacement therapy and control group for radiocontrast-induced nephropathy after coronary angiography procedure (baseline chronic kidney disease stage 3)

Ref.	Time from contrast exposure to the start of RRT (modes of RRT and duration)	No. of patients (RRT:control)	Incidence of RCIN results (RR, 95% CI)	Permanent dialysis rate of RCIN	In-hospital mortality of RCIN
Lehnert et al[70] (1998) diagnostic procedures	63 ± 6 min (HD 3 h)	30 (15:15)	8/15 vs 6/15 (RR = 1.33, 0.61-2.91)	NA	NA
Sterner et al[72] (2000) diagnostic procedures	< 3 h (HD 3 h)	32 (15:17)	6/15 vs 4/17 (RR = 1.70, 0.59-4.90)	NA	NA
Berger et al[71] (2001) diagnostic procedures	106 ± 25 min (HD 2–3 h)	15 (7:8)	3/7 vs 1/8 (RR = 3.43, 0.45-25.93)	NA	NA
Vogt et al[73] (2001) diagnostic procedures	2 h (HD 3 h)	113 (55:58)	24/55 vs 20/58 (RR = 1.27, 0.80-2.01)	3/55 vs 2/58 (RR = 1.58, 0.27-9.11)	1/55 vs 1/58 (RR = 1.06, 0.06-17.30)
Frank et al[74] (2003) diagnostic procedures	0 (HD 4 h)	17 (7:10)	NA	2/7 vs 2/10 (RR = 1.43, 0.26-7.86)	NA
Reinecke et al[78] (2007) diagnostic procedures	< 20 min (HD 4 h)	273 (135:139)	22/135 vs 10/138 (RR = 2.28, 1.12-4.64)	2/135 vs 1/137 (RR = 2.03, 0.19-22.12)	3/135 vs 3 137 (RR =1.02, 0.20-5.12)

RRT: Renal replacement therapy; HD: Hemodialysis; CVVH: Continuous venovenous hemofiltration; RCIN: Radiocontrast-induced nephropathy; CKD: Chronic kidney disease; RR: Relative risk; 95% CI: 95% confidence interval; NA: Not assessed.

Table 3 Clinical trials comparing prophylactic renal replacement therapy and control group for radiocontrast-induced nephropathy after coronary angiography procedure (Baseline chronic kidney disease stage 4-5)

Ref.	Time from contrast exposure to the start of RRT (modes of RRT and duration)	CKD stage, No. of patients (RRT:control)	Incidence of RCIN results (RR, 95% CI)	Permanent dialysis rate of RCIN	In-hospital mortality of RCIN
Marenzi et al[75] (2003) interventional procedures	0 (CVVH 22-30 h)	Stage 4, 114 (58:56)	4/58 vs 32/56 (RR = 0.12, 0.05-0.32)	2/58 vs 11/56 (RR = 0.18, 0.04-0.76)	1/58 vs 8/56 (RR = 0.11, 0.01-0.87)
Marenzi et al[76] (2006) diagnostic and interventional procedures	0 (CVVH 18-36 h)	Stage 4, 92 (62: 30)	9/62 vs 12/30 (RR = 0.36, 0.17-0.77)	NA	3/62 vs 6/30 (RR = 0.20, 0.05-0.88)
Lee et al[77] (2007) diagnostic procedures	81 ± 32 min (HD 4 h)	Stage 5, 82 (42:40)	2/42 vs 18/40 (RR = 0.11, 0.03-0.43)	0/42 vs 5/40 (RR = 0.09, 0-1.52)	No

RRT: Renal replacement therapy; HD: Hemodialysis; CVVH: Continuous venovenous hemofiltration; RCIN: Radiocontrast-induced nephropathy; CKD: Chronic kidney disease; RR: Relative risk; 95% CI: 95% confidence interval; NA: Not assessed.

Table 4 Clinical trials showing benefit of oral N-acetylcysteine for radiocontrast-induced nephropathy after angiography

Ref.	NAC dosing regimen (cumulated NAC dose)	No. of patients (NAC:control)	Hydration protocol	Contrast media type	Results
Shyu et al[88] (2002) coronary angiography	400 mg po bid before and after the procedure (1.6 g)	121 (60:61)	0.45% saline for 12 h pre- and 12 h postprocedure	LOCM iopamidol	3.3% vs 24.6% (P < 0.001)
Diaz-Sandoval[89] (2002) coronary angiography	600 mg po bid× 2, 1 dose before and 3 dose after the procedure (2.4 g)	54 (25:29)	0.45% saline for 2-12 h pre-and 12 h postprocedure	LOCM ioxilan	8.0% vs 45% (P = 0.005)
Kay et al[86] (2003) coronary angiography	600 mg po bid× 2, before and after the procedure (2.4 g)	200 (102:98)	0.9% saline for 12 h pre- and 6 h postprocedure;	LOCM iopamidol	3.9% vs 12.2% (P = 0.03)
MacNeill et al[90] (2003) coronary angiography	600 mg twice daily × 5 doses (3 g)	43 (21:22)	0.45% saline at a rate of 1 ml/kg per hour for 12 h for in-patients and 2 mL/kg per hour for 4 h for daycare patient	LOCM iopromide	5% vs 32% (P = 0.046)
Efrati et al[91] (2003) coronary angiography.	1000 mg po bid× 2, before and after the procedure (4 g)	49 (24:25)	0.45% saline hydration 1 mL/kg per hour for 12 h before and 12 h after coronary angiography	LOCM iopromide	0% vs 8%
Miner et al[92] (2004) coronary angiography	2000 mg po either 2 or 3 (4 g or 6 g)	180 (95:85)	0.45% intravenous saline	LOCM iohexol	9.6 % vs 22.2% (P = 0.04)
Briguori et al[87] (2004) cardiac/peripheral angiography	standard-dose 600 mg bid× 2 (2.4 g)	224 (110:114)	0.45% saline hydration 1 mL/kg per hour for 12 h before and 12 h after angiography	LOCM iobitridol	11.0% vs 3.5% (P = 0.038)

NAC: N-acetylcysteine; LOCM: Low-osmolar contrast media.

Table 5 Clinical trials comparing IV N-acetylcysteine and control after angiography procedure

Ref.	NAC dosing regimen (cumulated NAC dose)	No. of patients (NAC:hydration)	Hydration protocol	Contrast media type (mean dose)	Results
Baker et al[103] (2003) coronary angiography	150 mg/kg over 30 min before and 50 mg/kg over 4 h after (200 mg/kg)	41:39	0.9% NaCl 1 mL/kg per hour for 12 h pre- and post-procedure	IOCM iodixanol (253 mL)	5% vs 21% (RR = 0.28, P = 0.045)
Kefer et al[105] (2003) coronary angiography	1200 mg 12 h before 1200 mg immediately after the procedure (2.4 g)	53:51	0.9% NaCl 200 mL 12 h pre- and D5W 20 mL/h for 12 h pre and post-procedure	LOCM iopromide/iohexol (199 mL)	3.8% vs 5.9 % (P = 0.98)
Rashid et al[107] (2004) peripheral angiography	2 doses of 1000 mg at 6-12 h before and after the procedure (2 g)	46:48	2 doses of 0.9% NaCl 500 mL over 4-6 h at 6-12 h before and after the procedure	LOCM iohexol 143 mL)	pts. CrCl < 70 mL/min 7.7% vs 8.8% (P = 1.0)
Webb et al[109] (2004) coronary angiography	500 mg in D5W/0.9% NaCl 50 mL for 15 min as a bolus within 1 h before the procedure (500 mg)	242:245	D5W/0.9% NaCl 50 mL as a bolus within 1 h before the procedure and 200 mL 0.9% NaCl	LOCM ioversol (136 mL)	23.3% vs 20.7% (P = 0.51)
Kotlyar et al[110] (2005) cardiac or peripheral angiography	Gr 1: 300 mg × 2 (600 mg)	41:19	0.9% NaCl 1 mL/kg per hour	LOCM iopromide	0% vs 0 %
	Gr 2: 600 mg × 2 (1.2 g)
Carbonell et al[104] (2007) coronary angiography	600 mg twice daily (2.4 g)	107:109	0.45% intravenous saline	LOCM iopromide (193 mL)	10.3% vs 10.1% (P = 0.5)
Koc et al[102] (2010) coronary angiography and/or PCI	600 mg twice daily before and on the day of the coronary procedure (total = 2.4 g)	80:801:602	0.9% saline	LOCM iohexol 138 ± 47 mL)	2.5% vs 16.3% vs 10.0% (P = 0.012)

¹High-dose hydration group: IV 0.9% saline 1 mL/kg per hour before, on and after the day of coronary procedure (5334 ± 783 mL);

²Standard hydration group: IV 0.9% saline 1 mL/kg per hour for 12 h (1893 ± 270 mL). NAC: N-acetylcysteine; RCIN: Radiocontrast induced nephropathy; RR: Relative risk; CrCl: Creatinine clearance; NaCl: Sodium chloride; D5W: 5% dextrose; IOCM: Iso-osmolar contrast media; LOCM: Low-osmolar contrast media; PCI: Percutaneous coronary intervention.

Table 6 Clinical trials showing benefit of IV bicarbonate over saline to prevent radiocontrast-induced nephropathy after angiography

Ref.	Inclusion criteria	No. of patients	Hydration protocol	Contrast media type	Results: RCIN in bicarbonate group vs saline group	Dialysis and death rate
Merten et al[149] (2004) CT/coronary angiography	SCr ≥ 1.1 mg/dL	119	0.9% NaCl 1 mL/kg per hour for 12 h pre- and post-procedure	Iopamidol	1.7% vs 13.6% (P = 0.02)	Dialysis rate 0%
Ozcan et al[152] (2007) coronary angiography/PCI	SCr > 1.2 mg/dL	264	0.9% NaCl 200 mL 12 h pre- and D5W 20 mL/h for 12 h pre and post-procedure	Ioxaglate	4.5% vs 13.6% (P = 0.036)	Dialysis rate 1%
Briguori et al[150] (2007) coronary/peripheral angiography	SCr ≥ 2.0 mg/dL or eGFR < 40 mL/min per 1.73 m2	326	0.9% NaCl 500 mL over 4-6 h at 6-12 h before and after the procedure	Iodixanol	1.9% vs 9.9% (P = 0.019)	Dialysis rate 1%
Masuda et al[151] (2007) emergency coronary angiography/PCI	SCr ≥ 1.1 mg/dL or eGFR < 60 mL/min	59	D5W/0.9% NaCl 50 mL as a bolus within 1 h before the procedure and 200 mL 0.9% NaCl	Iopamidol	6.7% vs 34.5% (P = 0.01)	Dialysis rate 7%; death rate 3%
Recio-Mayoral et al[108] (2007) emergency PCI	None	111	Sodium bicarbonate 5 mL/kg per hour 1 h before the procedure and 1.5 mL/kg per hour for 12 h after the procedure	Iomeprol	1.8% vs 21.8% (P < 0.001)	Dialysis rate 4%; death rate 4.5%
Pakfetrat et al[153] (2009) coronary angiography/PCI	SCr > 1.2 mg/dL	192	Bicarbonate in dextrose infusion, normal saline infusion alone or combined with oral acetazolamide before procedure	Iodixanol	4.2% vs 12.5% (P < 0.001)	NA
Tamura et al[154] (2009) elective coronary angiography	SCr > 1.1 to < 2.0 mg/dL) undergoing an elective coronary	144	Single-bolus intravenous administration of sodium bicarbonate (20 mEq) immediately before contrast exposure	Iopamidol	10.3% vs 10.1% (P = 0.5)	NA
Ueda et al[155] (2011) emergent coronary procedures	SCr > 1.2 mg/dL	59	A bolus intravenous injection of 154 mEq/L of sodium bicarbonate or saline at the dose of 0.5 mL/kg, before CM, followed by infusion of 154 mEq/L sodium bicarbonate at 1 mL/kg per hour for 6 h in both groups	Iopamidol	3.3% vs 27.6% (P = 0.01)	NA

RCIN: Radiocontrast induced nephropathy; NaCl: Sodium chloride; D5W: 5% dextrose; PCI: Percutaneous coronary intervention; NA: Not assessed.

Table 7 Meta-analysis comparing the effectiveness of bicarbonate and saline to prevent radiocontrast-induced nephropathy

Ref.	Year of publication	No. of patients	No. of trials	Relative risk (95% CI) of RCIN of bicarbonate therapy compared with saline	Study heterogeneity and publication bias
Joannidis et al[160]	2008	2043	9	0.45 (0.26-0.79)	Heterogeneity detectable and publication bias was present
Hogan et al[161]	2008	1307	7	0.37 (0.18-0.714)	Evidence of heterogeneity
Ho et al[162]	2008	573	4	0.22 (0.11-0.44)	Significant heterogeneity
Meier et al[163]	2009	2633	17	0.52 (0.34-0.80)	Evidence of heterogeneity and publication bias
Navaneethan et al[166]	2009	1854	12	0.46 (0.26-0.82)	Heterogeneity and publication bias were detectable
Kanbay et al[165]	2009	2448	17	0.54 (0.36-0.83)	There are study heterogeneity and publication biases
Zoungas et al[168]	2009	3563	23	0.62 (0.45-0.86)	Evidence of heterogeneity and publication bias was present
Hoste et al[167]	2010	3055	18	0.66 (0.45-0.95)	Evidence of heterogeneity and publication bias was present
Trivedi et al[171]	2010	1090	10	0.57 (0.38-0.85)	No evidence of heterogeneity and no publication bias
Kunadian et al[170]	2011	1734	7	0.33 (0.16-0.69)	Heterogeneity and publication bias were detectable
Brown et al[164]	2009	1994	10	0.65 (0.40-1.05)	Significant heterogeneity
Brar et al[169]	2009	2290 (large trials, 1145; small trials, 1145)	14 (large trials 3; small trials 11)	large trials: 0.85 (0.63-1.16); small trials: 0.50 (0.27-0.93)	Evidence of publication bias; heterogeneity accounted for by trial size

RCIN: Radiocontrast-induced nephropathy; 95% CI: 95% confidence interval.