Review
Copyright ©The Author(s) 2017.
World J Nephrol. May 6, 2017; 6(3): 86-99
Published online May 6, 2017. doi: 10.5527/wjn.v6.i3.86
Table 1 Common indications for contrast media use in medical imaging
Diagnosis and treatment of vascular diseases such as coronary artery disease, pulmonary thromboembolism, arteriovenous malformations, aneurysms, arterial dissections and thrombosis
Diagnosis and staging of neoplastic diseases and mass lesions
Diagnosis of inflammatory and infectious diseases such as multiple sclerosis, meningitis, pancreatitis, diverticulitis
Table 2 Types, osmolalities and molecular structures of iodinated-contrast media
OsmolalityHigh osmolal (> 1400 mosm/kg)Low osmolal (500-850 mosm/kg)Iso-osmolal (290 mosm/kg)
Molecular structureIonic/monomerIonic/dimerNon-ionic/monomerNon-ionic/dimer
Name of moleculeDiatrizoate (Hypaque)Ioxaglate (Hexabrix)Iohexol (Omnipaque)Iodixanol (Visipaque)
Iopamidol (Isovue)
Ioversol (Optiray)
Iopromide (Ultravist)
Iopentol (Imagopaque)
Iomeprol (Iomeron)
Table 3 Major studies comparing low-osmolal and iso-osmolal contrast media in terms of renal safety
Ref.Baseline renal functions/patient populationProcedure/administration routeCompared drugsAim of the study/primary end pointsResults
Feldkamp et al[94]Normal GFRPTCA (intra-arterial)Iodixanol (IOCM) vs Iopromide (LOCM)≥ 25% increase in SCr at 48 hNo difference
Hardiek et al[95]Normal GFR, diabetic patientsPTCA (intra-arterial)Iodixanol (IOCM) vs Iopamidol (LOCM)≥ 25% increase in SCr days 1, 3 and 7No difference
Aspelin et al[96] (NEPHRIC)CKD, diabetic patientsPTCA (intra-arterial)Iodixanol (IOCM) vs Iohexol (LOCM)Peak increase in SCr day 0–3Iso-osmolal safer than low-osmolal CM
Jo et al[97] (RECOVER)CKDPTCA (intra-arterial)Iodixanol (IOCM) vs Ioxaglate (LOCM)Increase in SCr ≥ 25% or ≥ 0.5 mg/dL within 2 dIso-osmolal safer than low-osmolal CM
Solomon et al[98] (CARE)CKDPTCA (intra-arterial)Iodixanol (IOCM) vs Iopamidol (LOCM)Increase in SCr > 0.5 mg/dL at 45-120 hNo difference
Rudnick et al[99] (VALOR)CKDPTCA (intra-arterial)Iodixanol (IOCM) vs Ioversol (LOCM)Increase in SCr > 0.5 mg/dL within 72 hNo difference
Barrett et al[8] (IMPACT)CKDCT (intravenous)Iodixanol (IOCM) vs Iopamidol (LOCM)Increase in SCr > 0.5 mg/dL or ≥ 25% at 48–72 hNo difference
Kuhn et al[100] (PREDICT)CKDCT (intravenous)Iodixanol (IOCM) vs Iopamidol (LOCM)Increase in SCr > 0.5 mg/dL within 48-72 hNo difference
Thomsen et al[101] (ACTIVE)CKDCT (intravenous)Iodixanol (IOCM) vs Iomeprol (LOCM)Increase in SCr > 0.5 mg/dL at 48-72 hLow-osmolal safer than iso-osmolal CM
Nguyen et al[102]CKDCT (intravenous)Iodixanol (IOCM) vs Iopromide (LOCM)Peak rise in SCr days 1-3Iso-osmolal safer than low-osmolal CM
Wessely et al[103]CKDPTCA (intra-arterial)Iodixanol (IOCM) vs İomeprol (LOCM)Peak increase in SCrNo difference
Table 4 Meta-analyses comparing iso-osmolal and low-osmolal contrast media in terms of renal safety
MetaanalysesBaseline renal functionsProcedure/administration routeCompared drugsResults
McCullough et al[104] (16 trials)Both normal GFR and CKDPTCA (intra-arterial)Iodixanol (IOCM) vs various LOCMIodixanol safer than LOCM, e.p. in patients with CKD or CKD + diabetes mellitus
Reed et al[23] (16 trials)Both normal GFR and CKDPTCA + CT (intra-arterial + intravenous)Iodixanol (IOCM) vs various LOCMOverall, no difference. However, iodixanol safer than ioxaglate and iohexol
Heinrich et al[48] (25 trials)Both normal GFR and CKDPTCA + IV urography + CT (intra-arterial + intravenous)Iodixanol (IOCM) vs various LOCMOverall, no difference. However, iodixanol safer than iohexol in CKD patients when CM used via intra-arterial route
From et al[105] (36 trials)Both normal GFR and CKDPTCA + CT (intra-arterial + intravenous)Iodixanol (IOCM) vs various LOCMOverall, no difference. Iodixanol safer than iohexol
Eng et al[24] (29 trials)Both normal GFR and CKDPTCA + IV urography + CT (intra-arterial + intravenous)Iodixanol (IOCM) vs various LOCMIodixanol slightly safer than LOCM but the lower risk did not exceed a minimally important clinical difference
Table 5 Proposed pathophysiological mechanisms of contrast-induced acute kidney injury
Medullary vasoconstriction and hypoxia[27-29]
Direct cytotoxicity to renal tubular cells[30-33]
Release of vasoconstrictive mediators: Endothelin, adenosine, angiotensin II, vasopressin[28]
Reduction of vasodilatatory mediators: Nitric oxide, prostocyclin[28,32,34]
Increased oxidative stress[32,35,36]
Impairment of tubulo-glomerular feedback[32]
Increased blood and renal tubular viscosity[41]
Impairment of mitochondrial function and mitochondrial membrane potential[42]
Table 6 Patient-related and contrast media-related risk factors for contrast-induced acute kidney injury
Patient-related risk factors
Pre-existing CKD
Diabetes mellitus and diabetic nephropathy
Older age
Simultaneous use of nephrotoxic drugs
Multiple myeloma
States of reduced kidney perfusion
Dehydration
Congestive heart failure
Hemodynamic instability
Contrast-media related risk factors
High volume of CM
Use of hyperosmolal CM
Multiple exposure to CM in short-term
Intra-arterial administration
Table 7 Strategies to reduce the risk of contrast-induced acute kidney injury
Assess the risk of CI-AKI
Assess the need of contrast-enhancement, avoid unnecessary contrast administration
Avoid concomitant use of other nephrotoxic drugs
Hydrate the patient with isotonic saline and/or sodium bicarbonate before and after the procedure
N-acetyl-cysteine 1200 mg orally twice daily
Prefer iso-osmolal or hypo-osmolal CM
Use minimum amount of CM
Check renal functions within 1 wk of the procedure
Table 8 Experimental drugs and procedures to prevent contrast-induced acute kidney injury
Drugs
Hydration with isotonic saline[57-59]
N-acetyl-cysteine[69,106-110]
Sodium bicarbonate[58,68,108,109,111]
Theophylline[112-114]
Mannitol[115]
Furosemide[115-117]
Ascorbic acid (vitamin C)[118]
Tocopherol (vitamin E)[119]
Statins[120-124]
Mesna[125]
Dopamine[126]
Fenoldopam (dopamin agonist)[127]
Calcium channel blockers (verapamil, diltiazem)[128]
Adenosine[129]
Endothelin receptor antagonists[130]
Atrial natriuretic peptide[131]
Iloprost (PGI2 analogue)[132]
Misoprostol (PGE1 analogue)[133]
Trimetazidine[134]
Erythropoetin[135,136]
Nebivolol[137]
Sodium citrate[138]
Procedures
Remote ischemic preconditioning[72,73]
Prophylactic hemodialysis/hemofiltration/hemodiafiltration[71,139,140]
Table 9 Alternative non-contrast enhanced imaging techniques
Name of the techniqueClinical indicationsNotes
TOF MR angiographyCerebral aneurysmNo contrast agent is required
Stroke
Atherosclerotic carotid disease
Arteriovenous malformation
Peripheral artery disease (less frequently)
ECG-gated fast spin echo MR angiographyPeripheral artery diseaseNo contrast agent is required.
Thoraco-abdominal aortic aneurysmHigher image quality compared to TOF MR angiography in peripheral arterial imaging
SSFP MR imagingCoronary artery diseaseNo contrast agent is required
Myocardial viability and function
Pericardial diseases
Renal artery stenosis
Congenital heart diseases
Arterial spin labeling with/without SSFPNative and transplanted renal renal artery stenosisNo contrast agent is required.
Renal perfusionEvaluation of organ perfusion
Cerebral blood flowWhen combined with SSFP, it can be used as an angiographic imaging
Characterization of masses
Phase contrast MR imagingImaging of major thoroco-abdominal vascular structuresNo contrast agent is required.
Congenital heart diseaseQuantification of blood flow and velocity
Renal artery stenosis
Carbon-dioxide angiographyPeripheral artery disease (mostly infra-diaphragmatic)No contrast agent is required.
Non-allergenic, non-nephrotoxic, inexpensive.
Neurotoxic, risk of air trapping and distal ischemia