Ozkok S, Ozkok A. Contrast-induced acute kidney injury: A review of practical points. World J Nephrol 2017; 6(3): 86-99
Corresponding Author of This Article
Abdullah Ozkok, MD, Associate Professor, Department of Nephrology, Saglik Bilimleri University, Umraniye Training and Research Hospital, Selimiye Mah. Tibbiye Cad. No:38, 34722 Umraniye, Istanbul, Turkey. firstname.lastname@example.org
Checklist of Responsibilities for the Scientific Editor of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Contrast-induced acute kidney injury: A review of practical points
Sercin Ozkok, Abdullah Ozkok
Sercin Ozkok, Department of Radiology, Istanbul Medeniyet University, Goztepe Training and Research Hospital, 34760 Kadikoy, Istanbul, Turkey
Abdullah Ozkok, Department of Nephrology, Saglik Bilimleri University, Umraniye Training and Research Hospital, 34722 Umraniye, Istanbul, Turkey
ORCID number: $[AuthorORCIDs]
Author contributions: Ozkok S reviewed the literature and wrote the paper; Ozkok A designed and wrote the paper.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Abdullah Ozkok, MD, Associate Professor, Department of Nephrology, Saglik Bilimleri University, Umraniye Training and Research Hospital, Selimiye Mah. Tibbiye Cad. No:38, 34722 Umraniye, Istanbul, Turkey. email@example.com
Telephone: +90-21-66321818 Fax: +90-21-66327124
Received: January 21, 2017 Peer-review started: January 21, 2017 First decision: March 8, 2017 Revised: March 21, 2017 Accepted: April 18, 2017 Article in press: April 19, 2017 Published online: May 6, 2017
Contrast-induced acute kidney injury (CI-AKI) is one of the most common causes of AKI in clinical practice. CI-AKI has been found to be strongly associated with morbidity and mortality of the patients. Furthermore, CI-AKI may not be always reversible and it may be associated with the development of chronic kidney disease. Pathophysiology of CI-AKI is not exactly understood and there is no consensus on the preventive strategies. CI-AKI is an active research area thus clinicians should be updated periodically about this topic. In this review, we aimed to discuss the indications of contrast-enhanced imaging, types of contrast media and their impact on nephrotoxicity, major pathophysiological mechanisms, risk factors and preventive strategies of CI-AKI and alternative non-contrast-enhanced imaging methods.
Core tip: The best preventive measure of contrast-induced acute kidney injury is to avoid unnecessary contrast administration which requires a good knowledge of indications and risk factors of contrast-enhanced imaging. Recently, alternative non-contrast-enhanced imaging modalities have been developed which may help us to decrease the frequency of contrast administration. In this review, these alternative modalities are discussed concisely. Type, osmolality, molecular structure and viscosity of contrast media (CM) are important determinants of nephrotoxicity. Major studies and meta-analyses comparing CM in terms of renal safety are also discussed.
Citation: Ozkok S, Ozkok A. Contrast-induced acute kidney injury: A review of practical points. World J Nephrol 2017; 6(3): 86-99
Medical imaging has become an important diagnostic and therapeutic tool in clinical medicine in the era of great technological advances. Contrast media (CM) are increasingly used for better imaging in a broad spectrum of areas such as diagnostic computed tomography (CT) and magnetic resonance imaging (MRI), procedures of interventional radiology and percutaneous transluminal coronary angioplasty (PTCA). There are several adverse effects of CM including nausea, vomiting, thyroid dysfunction and hypersensitivity reactions such as urticaria, laryngeal edema, bronchospasm, hypotension and anaphylactoid shock.
Contrast-induced acute kidney injury (CI-AKI) is one of the most important adverse effects of CM. In the past, CI-AKI was considered to be a mild state with asymptomatic and transient elevations in serum creatinine values however recent studies have demonstrated that both short term and long-term mortality rates have been found to be significantly higher in patients with CI-AKI compared to patients without CI-AKI. Furthermore, a history of CI-AKI may be associated with development of chronic kidney disease (CKD) and progression to end-stage renal disease (ESRD) in long term[3,4].
In this review, we aimed to discuss the indications of contrast-enhanced imaging, types of CM and their impact on nephrotoxicity, major pathophysiological mechanism of CI-AKI, risk factors and preventive strategies of CI-AKI and alternative non-contrast-enhanced imaging methods.
DEFINITION OF CM
CM is a chemical substance which is used to improve the image quality of various body parts, to differentiate pathological from healthy tissues and to better delineate vascular structures. CM may be used by the way of oral route, intravascular or also through other luminal organs however absorption and nephrotoxic effects of CM used other than intravascular route may be negligible. In this review, the effects of intravascular administration of CM will be discussed.
DEFINITION OF CI-AKI
Various definitions of CI-AKI have been used in the literature. The most widely used definition is the increase in serum creatinine ≥ 0.5 mg/dL or 25% increase of serum creatinine from the baseline value at 48 h after CM administration. However timing of serum creatinine analysis after CM-enhanced imaging is controversial. Measurement as early as 12 h after the procedure (% change of creatinine from baseline) was found to significantly predict CI-AKI and furthermore it was associated with the development of renal damage after 30 d. Serum cystatin C levels have also been evaluated as an early marker of CI-AKI. In the study by Briguori et al performed on CKD patients undergoing PTCA, increase of cystatin C levels ≥ 10% at 24 h after the procedure was found to reliably predict the patients with high risk of CI-AKI.
EPIDEMIOLOGY OF CI-AKI
Incidence of CI-AKI in patients undergoing elective, non-emergent contrast-enhanced CT has been found to be very low, < 1%. In CKD patients, incidence of CI-AKI after intravenous CM administration was found to be 4%. However incidence of CI-AKI following contrast-enhanced CT performed in an emergency setting was found to be higher, > 10% which might reflect the underlying severe clinical status of the patient. Critically ill patients seem to be much more vulnerable to CI-AKI. In a study performed on critically ill patients without pre-existing renal disease, serum creatinine levels were elevated ≥ 25% from the baseline in 18% of the patients after CM-enhanced CT.
Incidence of CI-AKI in patients undergoing PTCA with normal baseline renal function was reported to be < 3%. However, the incidence of CI-AKI was found to be as high as 40% in CKD patients undergoing PTCA[12,13].
NEPHROTOXICITY OF MRI CONTRAST AGENTS
Until recently, MRI contrast agents also called gadolinium-based contrast agents (GBCA) have been considered to be safe in terms of nephrotoxicity. However GBCA has also been reported to cause AKI especially at high doses used for angiography in patients with pre-existing CKD and diabetic nephropathy[14-16]. In an in vitro study, cytotoxicity of GBCA was compared to that of iodinated CM in renal tubular cells at angiographic concentrations and GBCA was not less cytotoxic compared with iomeprol. In another study, urinary interleukin-18 and N-acetyl-glucosaminidase levels were found to increase transiently after administration of GBCA in patients with normal renal function. These results suggest that GBCA also induces cytotoxicity in renal tubular cells. Another important adverse effect of GBCA is the specific clinical entity called nephrogenic systemic fibrosis (NSF) which occurs especially in patients with CKD. NSF is a potentially mortal complication associated with GBCA.Recently, a relationship between previous gadolinium administrations and high signal intensity in the several parts of the brain has been suggested independent of renal function[19,20]. Gadolinium concentration in tissue was found to be strongly associated with cumulative gadolinium dose. Currently, clinical significance of gadolinium deposition in tissues is unclear, further studies are needed to clarify this issue.
In clinical practice, although GBCA are considered to be relatively safer than iodinated CM, risks of AKI, NSF and brain deposition should be kept in mind[14,16].
CLINICAL ISSUES NECESSITATING CM USE
It is important for clinicians to know the indications of contrast-enhanced imaging to avoid unnecessary contrast administration and its related complications. Common indications of CM use in clinical medicine are presented in Table 1. Accordingly, vascular, neoplastic and inflammatory diseases necessitate contrast-enhanced imaging. However CM is not usually suitable for the imaging of intracranial hemorrhages, cervical trauma, simple bone fractures, interstitial lung diseases and urinary system stones.
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
TYPES OF IODINATED CM AND THEIR IMPACT ON NEPHROTOXICITY
Type, osmolality, molecular structure and viscosity of CM are important determinants of nephrotoxicity associated with these agents (Table 2). Hyperosmolal CM (HOCM) was shown to more frequently cause CI-AKI compared with low-osmolal CM (LOCM). However HOCM are no more used in clinical practice. There are controversial results in studies comparing iso-osmolal CM (IOCM) and LOCM as seen in Table 3. In most of these studies, no difference was found between IOCM and LOCM in terms of renal safety. Meta-analyses comparing IOCM and LCOM are presented in Table 4. In the meta-analysis by Reed et al, iodixanol (IOCM) was found to be associated with a reduced risk of CI-AKI compared to iohexol (LOCM) however risk of CI-AKI was not significantly different between iodixanol and other LOCM. In a very recent meta-analysis by Eng et al, a modest decrease in the risk of CI-AKI was found with iodixanol (IOCM) when compared to other LOCM however no difference was found between the groups in terms of risk of renal replacement therapy, cardiovascular outcomes or death. Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommended to use LOCM or IOCM instead of HOCM however due to lack of reliable evidence, no recommendation was made about the preference of IOCM or LOCM.
Table 2 Types, osmolalities and molecular structures of iodinated-contrast media.
High osmolal (> 1400 mosm/kg)
Low osmolal (500-850 mosm/kg)
Iso-osmolal (290 mosm/kg)
Name of molecule
Table 3 Major studies comparing low-osmolal and iso-osmolal contrast media in terms of renal safety.
IOCM has lower osmolality compared with LOCM, however since IOCM has dimeric structure, it has higher viscosity than that of monomeric LOCM. Viscosity rather than osmolality determines the resistance to blood flow, thus IOCM may impair renal medullary blood flow to a greater extent compared to LOCM. Lack of clear superiority of IOCM over LOCM in terms of renal safety may be caused by higher viscosity of IOCM.
MAJOR PATHOPHYSIOLOGICAL MECHANISMS OF CI-AKI
Exact pathophysiological mechanism of CI-AKI is not known and includes complex cascades of events. Proposed mechanisms of CI-AKI are presented in Table 5. The most important elements of pathophysiological mechanism of CI-AKI seem to be the medullary hypoxia due to CM-induced medullary vasoconstriction[27-29] and direct renal tubular cytoxicity[30-33]. CM-induced vasoconstriction is not exactly understood but it is probably caused by an imbalance between vasoconstrictive (endothelin, adenosine) and vasodilatatory mediators (nitric oxide and prostocyclin)[28,32,34]. The contribution of oxidative stress seems to be an important and complementary event that further exacerbates CI-AKI[32,35,36].
Table 5 Proposed pathophysiological mechanisms of contrast-induced acute kidney injury.
Impairment of mitochondrial function and mitochondrial membrane potential
In normal physiological state, renal medullary blood flow and oxygen tension are relatively lower than those of the renal cortex. Furthermore, thick ascending limb located in the outer part of the renal medulla has a high-rate of ion transport with increased oxygen consumption exacerbating the relative hypoxia of the renal medulla. The most susceptible part of the nephron to hypoxia is well-known to be the renal medulla. CM is shown to decrase the oxygen tension of the renal medulla and simultaneously CM - induced osmotic diuresis causes increased sodium delivery to thick ascending limb leading to increased oxygen demand[27,37].
CM is known to cause direct mesangial and tubular cell toxicity. Proposed mechanisms of CM-induced cytotoxicity include oxidative stress, cellular energy failure, impaired cellular calcium homeostasis and increased apoptosis[33,38-40]. In the study by Peer et al, iodinated CM at different concentrations was found to induce apoptosis in both mesangial and tubular cells. The relationship between hypoxia, oxidative stress and direct cytotoxicity is not well-understood in the context of CI-AKI. Previously, a mismatch between the metabolic demands and the perfusion of renal medulla, in another words “relative hypoxia” was suggested to cause increased oxidative stress leading to further cytotoxicity. However, recently, in the study by Liu et al, CM-induced direct cytotoxicity has been shown to cause increased oxidative stress even in the absence of hypoxia. Oxidative stress seemed to be a consequence not a cause of renal tubular injury. Furthermore, in this study CM was found to increase tubuloglomerular feedback which might contribute to disturbances of renal perfusion and filtration. It may suggested that direct cytotoxicity of CM may be the primary event that pull the trigger rather than hypoxia, hypoperfusion or oxidative stress in the pathophysiological mechanism of CI-AKI.
CM - induced increase in blood and renal tubular viscosity may lead to resistance to blood flow and further exacerbate the medullary hypoxia. Another important mechanism may be the mitochondrial dysfunction, especially ionic CM was found to impair the mitochondrial functions and membrane potentials in proximal tubular cells.
RISK FACTORS FOR CI-AKI
Patients who are scheduled to have a contrast-enhanced diagnostic or interventional procedure should be evaluated for risk factors of CI-AKI (Table 6). Most important risk factors for CI-AKI are pre-existing CKD (GFR < 60 mL/min per 1.73 m2) and diabetes mellitus which may have additive effects on each other. In a study performed on patients undergoing contrast-enhanced CT, incidence of CI-AKI was found to be higher in diabetic CKD patients compared with non-diabetic CKD patients.
Table 6 Patient-related and contrast media-related risk factors for contrast-induced acute kidney injury.
Patient-related risk factors
Diabetes mellitus and diabetic nephropathy
Simultaneous use of nephrotoxic drugs
States of reduced kidney perfusion
Congestive heart failure
Contrast-media related risk factors
High volume of CM
Use of hyperosmolal CM
Multiple exposure to CM in short-term
CKD: Chronic kidney disease; CM: Contrast media.
Impacts of the type of imaging procedure and administration route of CM on CI-AKI
Type of the contrast-enhanced procedure seems to be an important determinant of CI-AKI. As aforementioned in this review, risk of CI-AKI with invasive PTCA seems to be higher compared to that of contrast-enhanced CT. This difference of the risk of CI-AKI between the two procedures may be caused by two reasons: (1) clinical status and comorbidities of the patients; and (2) administration route of the CM. Patients undergoing PTCA usually have significant ischemic heart disease and advanced atherosclerosis. During PTCA, significant hypotension may occur leading to ischemic nephropathy in addition to CI-AKI. Another important adverse event that may occur with invasive angiographic procedures is the cholesterol embolization syndrome (CES) which is sometimes hard to differentiate from CI-AKI. Administration route of the CM may also be important in the occurrence of CI-AKI. For contrast enhanced CT, CM is given intravenously, however in PTCA, CM is given intra-arterially. Risk of CI-AKI has been found to be higher with intra-arterial CM compared to intravenous CM administration especially when CM is used suprarenally[44,45]. With suprarenal intra-arterial administration of CM, peak CM concentration within the kidney was found to be higher. In the meta-analysis by Dong et al, risk of CI-AKI with intra-arterial iodixanol was found to be significantly lower when compared with intra-arterial LOCM. However no difference was found between IOCM and LOCM in terms of renal safety when CM was used intravenously. Similarly, in another meta-analysis by Heinrich et al, iodixanol was found to be safer than iohexol in CKD patients undergoing a procedure with intra-arterial CM administration. Iodixanol (IOCM) may be suggested to be a better choice for patients in the interventional cardiology setting.
Volume of CM
Lower doses of CM (definitions of low dose are variable: < 30-125 mL) were found to be less nephrotoxic[49,50]. In a study by Manske et al, low dose of CM was defined as < 5 mL/kg per serum creatinine. Recently, newer CT modalities have been developed using low tube voltage and low CM volume to reduce radiation exposure and the risk of CI-AKI without sacrificing image quality[51-53]. However it should be kept in mind that even very low doses of CM may lead to CI-AKI in patients with high risk factors.
RISK SCORING FOR CI-AKI
Several risk scoring systems have been developed to predict the CI-AKI. In the study by Mehran et al, CI-AKI was defined as an increase ≥ 25% and/or ≥ 0.5 mg/dL in serum creatinine at 48 h after PCI and they proposed a CI-AKI risk stratification score based on 8 readily available variables including (1) patient-related features such as age > 75 years, diabetes mellitus, chronic congestive heart failure (CHF), acute pulmonary edema, hypotension, anemia, and CKD; (2) procedure-related features such as the use of IABP or increasing volumes of CM. Integer scores of these risk factors were determined as: Hypotension, 5; IABP, 5; CHF, 5; age > 75 years, 4; anemia, 3; diabetes mellitus, 3; each 100 mL of CM, 1; serum creatinine > 1.5 mg/dL, 4; eGFR = 40-60 mL/min per 1.73 m2, 2; eGFR = 20-40 mL/min per 1.73 m2, 4; eGFR < 20 mL/min per 1.73 m2, 6. These scores are summed up and total risk score is obtained. For example, if total risk score is ≤ 5, risk of CI-AKI is 7.5% and risk of dialysis is 0.04%. However risk of CI-AKI is 57% and risk of dialysis is approximately 13% with a total risk score of ≥ 16. In conclusion, in this study, increasing total risk score was found to exponentially predict increased risk of CI-AKI. Another simple risk scoring for CI-AKI in patients undergoing PTCI is composed of age, creatinine and ejection fraction (ACEF score) which has been found to be an independent and useful predictor of CI-AKI defined as a rise in serum creatinine ≥ 0.5 mg/dL[55,56].
TREATMENT OF CI-AKI
There is no specific treatment for CI-AKI. There is no evidence that any of the preventive strategies are helpful once the CI-AKI develops. Similar to the management of other types of AKI, stabilization of hemodynamic paramaters and maintenance of normal fluid and electrolyte balance is crucial. Thus, prevention may be the only treatment modality for CI-AKI.
PREVENTION OF CI-AKI
Preventive strategies of CI-AKI are presented in Table 7. First things first, to prevent CI-AKI, avoid unnecessary contrast administration which requires good communication between the clinician and the radiologist. Clinicians should be informed about the medical imaging techniques alternative to contrast-enhanced medical imaging. If contrast use is inevitable, every patient should be evaluated for the risk factors for CI-AKI. Re-evaluation of concomitant use of other nephrotoxic drugs is of the utmost importance. Non-steroid anti-inflammatory drugs and nephrotoxic antibiotics such as aminoglycosides, colistin and antifungals such as amphotericin B should not be used if clinically possible.
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
In a prospective randomized study, hydration with isotonic (0.9% saline) and half-isotonic (0.45% sodium chloride plus 5% glucose) solutions were compared in terms of efficiency in prevention of CI-AKI in patients undergoing coronary angioplasty. Hydration was performed before, during and after the procedure and total amount of hydration was approximately 2000 mL. In this study, isotonic hydration was found to be superior to half-isotonic hydration in the prevention of CI-AKI. In a study performed on patients undergoing nonemergency cardiac catheterization, saline hydration starting from 12 h before the procedure was compared to unrestricted oral fluid intake. Patients in the first group received normal saline for 24 h (at a rate of 1 mL/kg per hour). Intravenous saline hydration was found to decrease the both incidence and severity of CI-AKI. In contrast, in a very recent prospective, randomized, non-inferiority study performed on CKD patients (eGFR: 30-59 mL/min per 1.73 m2) undergoing an elective procedure with CM, patients were randomly assigned to receive intravenous 0.9% NaCl or no prophylaxis. No prophylaxis group was found to be non-inferior to prophylaxis group and furthermore it was found to be cost-effective. However, despite the results of this study, we still strongly recommend hydration especially in patients with high risk of CI-AKI. Hypervolemia should be avoided during hydration of the patients. Monitorization of left ventricular end diastolic pressure was found to be a useful and effective way of guiding fluid replacement in a randomized controlled trial. Further studies are needed to prove the efficacy of hydration in prevention of CI-AKI.
There is controversy about the efficacy of sodium bicarbonate to prevent CI-AKI, several studies found sodium bicarbonate as protective against CI-AKI[62,63] while others found no beneficial effect[64-66]. In a meta-analysis, sodium bicarbonate was found to be protective against CI-AKI but with a borderline significance. In another 2 meta-analyses, no difference was found between bicarbonate and saline in terms of prevention from CI-AKI[67,68].
There is no standard dose of sodium bicarbonate for the prevention of CI-AKI. In a study, bicarbonate solution was prepared by adding 154 mL of 1000 mEq/L sodium bicarbonate to 846 mL of 5% dextrose in H2O. In this study, hydration with sodium bicarbonate before contrast exposure is more effective than hydration with sodium chloride for prophylaxis of CI-AKI. In another study, bicarbonate solution was prepared with 75 mL of 8.4% sodium bicarbonate added to 1 L of isotonic saline. In this study, no difference was found between sodium bicarbonate plus saline group and hyration with only saline group in terms of prevention from CI-AKI. Since sodium bicarbonate contains high amount of sodium, risk of hypervolemia should be taken into consideration especially in patients with congestive heart failure and CKD and dose of the bicarbonate should be individualized.
N-acetylcysteine (NAC) did not decrease the risk of CI-AKI in patients undergoing PTCA in a large randomized trial. There are several meta-analyses about the efficacy of NAC against CI-AKI with both non-significant and significant results. Although the strength of the evidence is low, NAC is a well tolerated, inexpensive drug and it has a relatively good profile of adverse effects. Thus, in 2012, KDIGO suggested NAC for patients with high risk of CI-AKI. There is no consensus on the dose of the NAC however it is usually used at a dose of 600-1200 mg orally twice daily.
Prophylactic hemodialysis (HD) and hemofiltration (HF) were not found to be protective against CI-AKI. In the meta-analysis including 8 studies of HD and 3 studies of HF, no beneficial effects of these treatment modalities was found against CI-AKI. Furthermore, HD was found to increase the risk of CI-AKI. Thus prophylactic renal replacement treatments are not recommended.
Remote ischemic preconditioning
Remote ischemic preconditioning (RIP) is an interesting procedure that has been evaluated as a potential protective mechanism of CI-AKI. RIP depends on a hypothesis that a transient ischemia of an organ may protect against an ischemic injury of another distant organ. Mostly, RIP has been induced by arm ischemia performed by inflation of blood pressure cuffs. In preliminary studies, RIP has been found to decrease the risk of CI-AKI[72,73]. However further randomized clinical trials are needed before a recommendation can be made.
Should we stop ACEI/ARB treatments before the contrast-enhanced imaging?
Some clinicians may prefer to stop angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) before the contrast administration because ACEI/ARB are considered to increase the risk of CI-AKI. Supporting these concerns, in a retrospective study, use of ACEI/ARBs during PTCA was found to be independently associated with increased risk of CI-AKI. However in a prospective randomized trial, discontinuation of ACEI/ARB treatments 24 h before PTCA did not influence the incidence of CI-AKI in patients with CKD. We think that, cessation of ACEI/ARB treatments for only 1 d before the procedure might not be adequate because renal hemodynamic effects of these drugs might last longer. In a very recent meta-analysis, ACEI use was not found to have a significant effect on the CI-AKI in patients undergoing PTCA. In summary, there is not enough evidence to recommend withholding or continuing ACEI/ARB treatments before contrast-enhanced imaging.
Should we stop metformin treatment before the contrast-enhanced imaging?
Metformin is not a nephrotoxic drug however it is excreted by the kidney. Metformin is known to cause severe lactic acidosis in patients with renal impairment. About 8% of cases reporting metformin induced lactic acidosis were found to be associated with CI-AKI. Cessation of metformin at least 48 h before the contrast administration is a common but controversial clinical practice. According to other researchers, the risk of metformin induced lactic acidosis is extremely low in patients with normal renal function thus discontinuation of metformin is considered unnecessary in non-uremic patients. We think that it will be appropriate to discontinue metformin especially in CKD patients who are planned to have a contrast-enhanced procedure.
ALTERNATIVE NON-CONTRAST ENHANCED IMAGING TECHNIQUES
In the era of rapidly evolving technology, new non-contrast-enhanced imaging modalities have been developed (Table 9). Most of these modalities are MRI-based techniques. Knowledge of these new techniques may be beneficial for the renal health of the patients needing contrast-enhanced imaging and interventions. Preference of these imaging modalities may be discussed between the clinician and radiologist.
Table 9 Alternative non-contrast enhanced imaging techniques.
Name of the technique
TOF MR angiography
No contrast agent is required
Atherosclerotic carotid disease
Peripheral artery disease (less frequently)
ECG-gated fast spin echo MR angiography
Peripheral artery disease
No contrast agent is required.
Thoraco-abdominal aortic aneurysm
Higher image quality compared to TOF MR angiography in peripheral arterial imaging
SSFP MR imaging
Coronary artery disease
No contrast agent is required
Myocardial viability and function
Renal artery stenosis
Congenital heart diseases
Arterial spin labeling with/without SSFP
Native and transplanted renal renal artery stenosis
No contrast agent is required.
Evaluation of organ perfusion
Cerebral blood flow
When combined with SSFP, it can be used as an angiographic imaging
Characterization of masses
Phase contrast MR imaging
Imaging of major thoroco-abdominal vascular structures
There are two concerns about the use of iodinated CM in patients with ESRD; risk of loss of residual renal function (RRF) and CM-induced hypervolemia.
RRF is associated with better outcome and survival in patients with ESRD. Thus it should be preserved by avoiding unnecessary use of CM and nephrotoxic drugs. HD treatment after iodinated CM exposure was not shown to preserve RRF in patients with ESRD.
Another concern about the contrast administration is the hypervolemia that may be induced by the CM. Sometimes clinicians may prefer to perform HD immediately after contrast enhanced imaging. However as reported by Hamani et al, new non-ionic LOCM does not seem to increase serum osmolality, arterial blood pressure and it does not cause hypervolemia. Thus immediate HD may not be warranted to prevent hypervolemia in stable chronic HD patients.
GBCA should be better avoided in ESRD patients because of the risk of potentially mortal complication: NSF which is a systemic fibrosing disease that occurs due to exposure to GBCA especially in patients with GFR < 30 mL/min. If it is inevitable to use GBCA in ESRD patients, immediate HD after the imaging procedure should be considered because GBCA has been shown to be effectively removed by HD. However no proof exists that HD after GBCA exposure reduces the risk of NSF.
In HD patients without urine output (no RRF), if contrast-enhanced imaging is required, CT is clearly preferred over MRI to avoid the risk of NSF.
PROGNOSIS OF CI-AKI
Short and long term mortalities of patients with CI-AKI have been shown to be higher compared with patients without CI-AKI[85-87]. However there are few studies about the long-term renal prognosis of patients who developed CI-AKI. In a prospective study performed on patients with symptomatic peripheral artery disease undergoing PTCA, patients with CI-AKI were found to be at increased risk of long-term loss of renal function, cardiovascular events, and death. In this study, one year after the procedure, decline in eGFR was significantly higher in patients with CI-AKI compared with patients without CI-AKI (12.4 mL/min vs 6.2 mL/min). In another observational study on CKD patients undergoing PTCA, persistent renal dysfunction was defined as the decrease of creatinine clearance ≥ 25% of baseline values at 3 mo. In this study, overall incidence of CI-AKI was found to be 12%, and persistent renal dysfunction was found in 18.6% of CI-AKI patients. Similarly, in another study performed on patients undergoing PTCA, continuous deterioration of kidney function (CDKF) was defined as > 25% increase in serum creatinine or serum creatinine > 0.5 mg/dL above baseline at 6 to 8 mo after PTCA. In this study CDFK was found in 16% of the study population and this group of patients was found to have significantly higher 5-year mortality rate. In a large study performed to find the incidence of CKD onset after PTCA, incidence of new-onset CKD within 6 mo of the procedure was found to be 0.9%. Furthermore, in this study trans-radial access site was found to be associated with less CKD than the femoral approach.
The most important alternative diagnosis of AKI after contrast-enhanced imaging especially PTCA is the CES which is rarer than CI-AKI however long-term renal survival is significantly worse than CI-AKI. CES manifests later than CI-AKI, usually 1-2 wk after the procedure. Dislodgement of cholesterol crystals from the atherosclerotic plaques leads to embolization of the small peripheral arterioles causing a multisystemic disease with allergic-immunological features including eosinophilia, hypocomplementemia, livedo reticularis, distal gangrenes with palpable pulses (blue-toe syndrome) and pathognomonic Hollenhorst plaques on ophthalmologic examination. Renal biopsy reveals empty clefts within the obliterated lumens of the arterioles. Differentiation of CI-AKI and CES is important because these two diseases may have different types of treatment modalities. Once developed, CI-AKI necessitates only supportive measures. However since CES is a type of allergic-immunological disease, anti-inflammatory treatments such as corticosteroids and cyclophosphamide may be considered[92,93]. But there is no proof of efficacy of these anti-inflammatory treatments on CES.
Manuscript source: Invited manuscript
Specialty type: Urology and nephrology
Country of origin: Turkey
Peer-review report classification
Grade A (Excellent): A
Grade B (Very good): 0
Grade C (Good): C, C, C
Grade D (Fair): 0
Grade E (Poor): 0
P- Reviewer: Sabate M, Schoenhagen P, Tomizawa M, Zuo L S- Editor: Song XX L- Editor: A E- Editor: Li D
Bottinor W, Polkampally P, Jovin I. Adverse reactions to iodinated contrast media.Int J Angiol. 2013;22:149-154.
Rudnick M, Feldman H. Contrast-induced nephropathy: what are the true clinical consequences?Clin J Am Soc Nephrol. 2008;3:263-272.
Maioli M, Toso A, Leoncini M, Gallopin M, Musilli N, Bellandi F. Persistent renal damage after contrast-induced acute kidney injury: incidence, evolution, risk factors, and prognosis.Circulation. 2012;125:3099-3107.
Nemoto N, Iwasaki M, Nakanishi M, Araki T, Utsunomiya M, Hori M, Ikeda N, Makino K, Itaya H, Iijima R. Impact of continuous deterioration of kidney function 6 to 8 months after percutaneous coronary intervention for acute coronary syndrome.Am J Cardiol. 2014;113:1647-1651.
Ribichini F, Graziani M, Gambaro G, Pasoli P, Pighi M, Pesarini G, Abaterusso C, Yabarek T, Brunelleschi S, Rizzotti P. Early creatinine shifts predict contrast-induced nephropathy and persistent renal damage after angiography.Am J Med. 2010;123:755-763.
Briguori C, Visconti G, Rivera NV, Focaccio A, Golia B, Giannone R, Castaldo D, De Micco F, Ricciardelli B, Colombo A. Cystatin C and contrast-induced acute kidney injury.Circulation. 2010;121:2117-2122.
Weisbord SD, Mor MK, Resnick AL, Hartwig KC, Palevsky PM, Fine MJ. Incidence and outcomes of contrast-induced AKI following computed tomography.Clin J Am Soc Nephrol. 2008;3:1274-1281.
Barrett BJ, Katzberg RW, Thomsen HS, Chen N, Sahani D, Soulez G, Heiken JP, Lepanto L, Ni ZH, Ni ZH. Contrast-induced nephropathy in patients with chronic kidney disease undergoing computed tomography: a double-blind comparison of iodixanol and iopamidol.Invest Radiol. 2006;41:815-821.
Mitchell AM, Jones AE, Tumlin JA, Kline JA. Incidence of contrast-induced nephropathy after contrast-enhanced computed tomography in the outpatient setting.Clin J Am Soc Nephrol. 2010;5:4-9.
Polena S, Yang S, Alam R, Gricius J, Gupta JR, Badalova N, Chuang P, Gintautas J, Conetta R. Nephropathy in critically Ill patients without preexisting renal disease.Proc West Pharmacol Soc. 2005;48:134-135.
Rihal CS, Textor SC, Grill DE, Berger PB, Ting HH, Best PJ, Singh M, Bell MR, Barsness GW, Mathew V. Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention.Circulation. 2002;105:2259-2264.
Chong E, Shen L, Poh KK, Tan HC. Risk scoring system for prediction of contrast-induced nephropathy in patients with pre-existing renal impairment undergoing percutaneous coronary intervention.Singapore Med J. 2012;53:164-169.
Marenzi G, Lauri G, Assanelli E, Campodonico J, De Metrio M, Marana I, Grazi M, Veglia F, Bartorelli AL. Contrast-induced nephropathy in patients undergoing primary angioplasty for acute myocardial infarction.J Am Coll Cardiol. 2004;44:1780-1785.
Penfield JG, Reilly RF. What nephrologists need to know about gadolinium.Nat Clin Pract Nephrol. 2007;3:654-668.
Fujisaki K, Ono-Fujisaki A, Kura-Nakamura N, Komune N, Hirakawa N, Tsuruya K, Komune S, Iida M. Rapid deterioration of renal insufficiency after magnetic resonance imaging with gadolinium-based contrast agent.Clin Nephrol. 2011;75:251-254.
Perazella MA. Current status of gadolinium toxicity in patients with kidney disease.Clin J Am Soc Nephrol. 2009;4:461-469.
Heinrich MC, Kuhlmann MK, Kohlbacher S, Scheer M, Grgic A, Heckmann MB, Uder M. Cytotoxicity of iodinated and gadolinium-based contrast agents in renal tubular cells at angiographic concentrations: in vitro study.Radiology. 2007;242:425-434.
Mawad H, Laurin LP, Naud JF, Leblond FA, Henley N, Vallée M, Pichette V, Leblanc M. Changes in Urinary and Serum Levels of Novel Biomarkers after Administration of Gadolinium-based Contrast Agents.Biomark Insights. 2016;11:91-94.
Kanda T, Ishii K, Kawaguchi H, Kitajima K, Takenaka D. High signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted MR images: relationship with increasing cumulative dose of a gadolinium-based contrast material.Radiology. 2014;270:834-841.
Olchowy C, Cebulski K, Łasecki M, Chaber R, Olchowy A, Kałwak K, Zaleska-Dorobisz U. The presence of the gadolinium-based contrast agent depositions in the brain and symptoms of gadolinium neurotoxicity - A systematic review.PLoS One. 2017;12:e0171704.
Lautin EM, Freeman NJ, Schoenfeld AH, Bakal CW, Haramati N, Friedman AC, Lautin JL, Braha S, Kadish EG. Radiocontrast-associated renal dysfunction: a comparison of lower-osmolality and conventional high-osmolality contrast media.AJR Am J Roentgenol. 1991;157:59-65.
Reed M, Meier P, Tamhane UU, Welch KB, Moscucci M, Gurm HS. The relative renal safety of iodixanol compared with low-osmolar contrast media: a meta-analysis of randomized controlled trials.JACC Cardiovasc Interv. 2009;2:645-654.
Eng J, Wilson RF, Subramaniam RM, Zhang A, Suarez-Cuervo C, Turban S, Choi MJ, Sherrod C, Hutfless S, Iyoha EE. Comparative Effect of Contrast Media Type on the Incidence of Contrast-Induced Nephropathy: A Systematic Review and Meta-analysis.Ann Intern Med. 2016;164:417-424.
KDIGO. Clinical Practice Guideline for Acute Kidney Injury.Kidney Int Suppl. 2012;2:8.
Persson PB, Hansell P, Liss P. Pathophysiology of contrast medium-induced nephropathy.Kidney Int. 2005;68:14-22.
Heyman SN, Brezis M, Epstein FH, Spokes K, Silva P, Rosen S. Early renal medullary hypoxic injury from radiocontrast and indomethacin.Kidney Int. 1991;40:632-642.
Sendeski M, Patzak A, Pallone TL, Cao C, Persson AE, Persson PB. Iodixanol, constriction of medullary descending vasa recta, and risk for contrast medium-induced nephropathy.Radiology. 2009;251:697-704.
Liss P, Nygren A, Erikson U, Ulfendahl HR. Injection of low and iso-osmolar contrast medium decreases oxygen tension in the renal medulla.Kidney Int. 1998;53:698-702.
Nazıroğlu M, Yoldaş N, Uzgur EN, Kayan M. Role of contrast media on oxidative stress, Ca(2+) signaling and apoptosis in kidney.J Membr Biol. 2013;246:91-100.
Quintavalle C, Brenca M, De Micco F, Fiore D, Romano S, Romano MF, Apone F, Bianco A, Zabatta MA, Troncone G. In vivo and in vitro assessment of pathways involved in contrast media-induced renal cells apoptosis.Cell Death Dis. 2011;2:e155.
Liu ZZ, Schmerbach K, Lu Y, Perlewitz A, Nikitina T, Cantow K, Seeliger E, Persson PB, Patzak A, Liu R. Iodinated contrast media cause direct tubular cell damage, leading to oxidative stress, low nitric oxide, and impairment of tubuloglomerular feedback.Am J Physiol Renal Physiol. 2014;306:F864-F872.
Peer A, Averbukh Z, Berman S, Modai D, Averbukh M, Weissgarten J. Contrast media augmented apoptosis of cultured renal mesangial, tubular, epithelial, endothelial, and hepatic cells.Invest Radiol. 2003;38:177-182.
Ribeiro L, de Assunção e Silva F, Kurihara RS, Schor N, Mieko E, Higa S. Evaluation of the nitric oxide production in rat renal artery smooth muscle cells culture exposed to radiocontrast agents.Kidney Int. 2004;65:589-596.
Bakris GL, Lass N, Gaber AO, Jones JD, Burnett JC. Radiocontrast medium-induced declines in renal function: a role for oxygen free radicals.Am J Physiol. 1990;258:F115-F120.
Heyman SN, Rosen S, Khamaisi M, Idée JM, Rosenberger C. Reactive oxygen species and the pathogenesis of radiocontrast-induced nephropathy.Invest Radiol. 2010;45:188-195.
Itoh Y, Yano T, Sendo T, Sueyasu M, Hirano K, Kanaide H, Oishi R. Involvement of de novo ceramide synthesis in radiocontrast-induced renal tubular cell injury.Kidney Int. 2006;69:288-297.
Schick CS, Haller C. Comparative cytotoxicity of ionic and non-ionic radiocontrast agents on MDCK cell monolayers in vitro.Nephrol Dial Transplant. 1999;14:342-347.
Haller C, Hizoh I. The cytotoxicity of iodinated radiocontrast agents on renal cells in vitro.Invest Radiol. 2004;39:149-154.
Zhang Y, Wang J, Yang X, Wang X, Zhang J, Fang J, Jiang X. The serial effect of iodinated contrast media on renal hemodynamics and oxygenation as evaluated by ASL and BOLD MRI.Contrast Media Mol Imaging. 2012;7:418-425.
Hardiek K, Katholi RE, Ramkumar V, Deitrick C. Proximal tubule cell response to radiographic contrast media.Am J Physiol Renal Physiol. 2001;280:F61-F70.
Parfrey PS, Griffiths SM, Barrett BJ, Paul MD, Genge M, Withers J, Farid N, McManamon PJ. Contrast material-induced renal failure in patients with diabetes mellitus, renal insufficiency, or both. A prospective controlled study.N Engl J Med. 1989;320:143-149.
Moore RD, Steinberg EP, Powe NR, Brinker JA, Fishman EK, Graziano S, Gopalan R. Nephrotoxicity of high-osmolality versus low-osmolality contrast media: randomized clinical trial.Radiology. 1992;182:649-655.
Li J, Solomon RJ. Creatinine increases after intravenous contrast administration: incidence and impact.Invest Radiol. 2010;45:471-476.
Gleeson TG, Bulugahapitiya S. Contrast-induced nephropathy.AJR Am J Roentgenol. 2004;183:1673-1689.
Dong M, Jiao Z, Liu T, Guo F, Li G. Effect of administration route on the renal safety of contrast agents: a meta-analysis of randomized controlled trials.J Nephrol. 2012;25:290-301.
Heinrich MC, Häberle L, Müller V, Bautz W, Uder M. Nephrotoxicity of iso-osmolar iodixanol compared with nonionic low-osmolar contrast media: meta-analysis of randomized controlled trials.Radiology. 2009;250:68-86.
Manske CL, Sprafka JM, Strony JT, Wang Y. Contrast nephropathy in azotemic diabetic patients undergoing coronary angiography.Am J Med. 1990;89:615-620.
Cigarroa RG, Lange RA, Williams RH, Hillis LD. Dosing of contrast material to prevent contrast nephropathy in patients with renal disease.Am J Med. 1989;86:649-652.
Zhang LJ, Qi L, Wang J, Tang CX, Zhou CS, Ji XM, Spearman JV, De Cecco CN, Meinel FG, Schoepf UJ. Feasibility of prospectively ECG-triggered high-pitch coronary CT angiography with 30 mL iodinated contrast agent at 70 kVp: initial experience.Eur Radiol. 2014;24:1537-1546.
Chen CM, Chu SY, Hsu MY, Liao YL, Tsai HY. Low-tube-voltage (80 kVp) CT aortography using 320-row volume CT with adaptive iterative reconstruction: lower contrast medium and radiation dose.Eur Radiol. 2014;24:460-468.
Szucs-Farkas Z, Schaller C, Bensler S, Patak MA, Vock P, Schindera ST. Detection of pulmonary emboli with CT angiography at reduced radiation exposure and contrast material volume: comparison of 80 kVp and 120 kVp protocols in a matched cohort.Invest Radiol. 2009;44:793-799.
Mehran R, Aymong ED, Nikolsky E, Lasic Z, Iakovou I, Fahy M, Mintz GS, Lansky AJ, Moses JW, Stone GW. A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: development and initial validation.J Am Coll Cardiol. 2004;44:1393-1399.
Ranucci M, Castelvecchio S, Menicanti L, Frigiola A, Pelissero G. Risk of assessing mortality risk in elective cardiac operations: age, creatinine, ejection fraction, and the law of parsimony.Circulation. 2009;119:3053-3061.
Capodanno D, Ministeri M, Dipasqua F, Dalessandro V, Cumbo S, Gargiulo G, Tamburino C. Risk prediction of contrast-induced nephropathy by ACEF score in patients undergoing coronary catheterization.J Cardiovasc Med (Hagerstown). 2016;17:524-529.
Mueller C, Buerkle G, Buettner HJ, Petersen J, Perruchoud AP, Eriksson U, Marsch S, Roskamm H. Prevention of contrast media-associated nephropathy: randomized comparison of 2 hydration regimens in 1620 patients undergoing coronary angioplasty.Arch Intern Med. 2002;162:329-336.
Klima T, Christ A, Marana I, Kalbermatter S, Uthoff H, Burri E, Hartwiger S, Schindler C, Breidthardt T, Marenzi G. Sodium chloride vs. sodium bicarbonate for the prevention of contrast medium-induced nephropathy: a randomized controlled trial.Eur Heart J. 2012;33:2071-2079.
Trivedi HS, Moore H, Nasr S, Aggarwal K, Agrawal A, Goel P, Hewett J. A randomized prospective trial to assess the role of saline hydration on the development of contrast nephrotoxicity.Nephron Clin Pract. 2003;93:C29-C34.
Nijssen EC, Rennenberg RJ, Nelemans PJ, Essers BA, Janssen MM, Vermeeren MA, Ommen VV, Wildberger JE. Prophylactic hydration to protect renal function from intravascular iodinated contrast material in patients at high risk of contrast-induced nephropathy (AMACING): a prospective, randomised, phase 3, controlled, open-label, non-inferiority trial.Lancet. 2017;389:1312-1322.
Brar SS, Aharonian V, Mansukhani P, Moore N, Shen AY, Jorgensen M, Dua A, Short L, Kane K. Haemodynamic-guided fluid administration for the prevention of contrast-induced acute kidney injury: the POSEIDON randomised controlled trial.Lancet. 2014;383:1814-1823.
Merten GJ, Burgess WP, Gray LV, Holleman JH, Roush TS, Kowalchuk GJ, Bersin RM, Van Moore A, Simonton CA, Rittase RA. Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial.JAMA. 2004;291:2328-2334.
Hoste EA, De Waele JJ, Gevaert SA, Uchino S, Kellum JA. Sodium bicarbonate for prevention of contrast-induced acute kidney injury: a systematic review and meta-analysis.Nephrol Dial Transplant. 2010;25:747-758.
Brar SS, Shen AY, Jorgensen MB, Kotlewski A, Aharonian VJ, Desai N, Ree M, Shah AI, Burchette RJ. Sodium bicarbonate vs sodium chloride for the prevention of contrast medium-induced nephropathy in patients undergoing coronary angiography: a randomized trial.JAMA. 2008;300:1038-1046.
Vasheghani-Farahani A, Sadigh G, Kassaian SE, Khatami SM, Fotouhi A, Razavi SA, Mansournia MA, Yamini-Sharif A, Amirzadegan A, Salarifar M. Sodium bicarbonate plus isotonic saline versus saline for prevention of contrast-induced nephropathy in patients undergoing coronary angiography: a randomized controlled trial.Am J Kidney Dis. 2009;54:610-618.
Solomon R, Gordon P, Manoukian SV, Abbott JD, Kereiakes DJ, Jeremias A, Kim M, Dauerman HL; BOSS Trial Investigators. Randomized Trial of Bicarbonate or Saline Study for the Prevention of Contrast-Induced Nephropathy in Patients with CKD.Clin J Am Soc Nephrol. 2015;10:1519-1524.
Subramaniam RM, Suarez-Cuervo C, Wilson RF, Turban S, Zhang A, Sherrod C, Aboagye J, Eng J, Choi MJ, Hutfless S. Effectiveness of Prevention Strategies for Contrast-Induced Nephropathy: A Systematic Review and Meta-analysis.Ann Intern Med. 2016;164:406-416.
Brar SS, Hiremath S, Dangas G, Mehran R, Brar SK, Leon MB. Sodium bicarbonate for the prevention of contrast induced-acute kidney injury: a systematic review and meta-analysis.Clin J Am Soc Nephrol. 2009;4:1584-1592.
ACT Investigators. Acetylcysteine for prevention of renal outcomes in patients undergoing coronary and peripheral vascular angiography: main results from the randomized Acetylcysteine for Contrast-induced nephropathy Trial (ACT).Circulation. 2011;124:1250-1259.
Zagler A, Azadpour M, Mercado C, Hennekens CH. N-acetylcysteine and contrast-induced nephropathy: a meta-analysis of 13 randomized trials.Am Heart J. 2006;151:140-145.
Cruz DN, Goh CY, Marenzi G, Corradi V, Ronco C, Perazella MA. Renal replacement therapies for prevention of radiocontrast-induced nephropathy: a systematic review.Am J Med. 2012;125:66-78.e3.
Igarashi G, Iino K, Watanabe H, Ito H. Remote ischemic pre-conditioning alleviates contrast-induced acute kidney injury in patients with moderate chronic kidney disease.Circ J. 2013;77:3037-3044.
Er F, Nia AM, Dopp H, Hellmich M, Dahlem KM, Caglayan E, Kubacki T, Benzing T, Erdmann E, Burst V. Ischemic preconditioning for prevention of contrast medium-induced nephropathy: randomized pilot RenPro Trial (Renal Protection Trial).Circulation. 2012;126:296-303.
Rim MY, Ro H, Kang WC, Kim AJ, Park H, Chang JH, Lee HH, Chung W, Jung JY. The effect of renin-angiotensin-aldosterone system blockade on contrast-induced acute kidney injury: a propensity-matched study.Am J Kidney Dis. 2012;60:576-582.
Rosenstock JL, Bruno R, Kim JK, Lubarsky L, Schaller R, Panagopoulos G, DeVita MV, Michelis MF. The effect of withdrawal of ACE inhibitors or angiotensin receptor blockers prior to coronary angiography on the incidence of contrast-induced nephropathy.Int Urol Nephrol. 2008;40:749-755.
Zhou S, Wu C, Song Q, Yang X, Wei Z. Effect of Angiotensin-Converting Enzyme Inhibitors in Contrast-Induced Nephropathy: A Meta-Analysis.Nephron. 2016;133:1-14.
Sirtori CR, Pasik C. Re-evaluation of a biguanide, metformin: mechanism of action and tolerability.Pharmacol Res. 1994;30:187-228.
Thomsen HS, Morcos SK. Contrast media and metformin: guidelines to diminish the risk of lactic acidosis in non-insulin-dependent diabetics after administration of contrast media. ESUR Contrast Media Safety Committee.Eur Radiol. 1999;9:738-740.
Owen RJ, Hiremath S, Myers A, Fraser-Hill M, Barrett BJ. Canadian Association of Radiologists consensus guidelines for the prevention of contrast-induced nephropathy: update 2012.Can Assoc Radiol J. 2014;65:96-105.
Shemin D, Bostom AG, Laliberty P, Dworkin LD. Residual renal function and mortality risk in hemodialysis patients.Am J Kidney Dis. 2001;38:85-90.
Rodby RA. Preventing complications of radiographic contrast media: is there a role for dialysis?Semin Dial. 2007;20:19-23.
Hamani A, Petitclerc T, Jacobs C, Deray G. Is dialysis indicated immediately after administration of iodinated contrast agents in patients on haemodialysis?Nephrol Dial Transplant. 1998;13:1051-1052.
Kuo PH, Kanal E, Abu-Alfa AK, Cowper SE. Gadolinium-based MR contrast agents and nephrogenic systemic fibrosis.Radiology. 2007;242:647-649.
Saitoh T, Hayasaka K, Tanaka Y, Kuno T, Nagura Y. Dialyzability of gadodiamide in hemodialysis patients.Radiat Med. 2006;24:445-451.
Kim JH, Yang JH, Choi SH, Song YB, Hahn JY, Choi JH, Lee SH, Gwon HC. Predictors of outcomes of contrast-induced acute kidney injury after percutaneous coronary intervention in patients with chronic kidney disease.Am J Cardiol. 2014;114:1830-1835.
Weisbord SD, Chen H, Stone RA, Kip KE, Fine MJ, Saul MI, Palevsky PM. Associations of increases in serum creatinine with mortality and length of hospital stay after coronary angiography.J Am Soc Nephrol. 2006;17:2871-2877.
McCullough PA, Wolyn R, Rocher LL, Levin RN, O’Neill WW. Acute renal failure after coronary intervention: incidence, risk factors, and relationship to mortality.Am J Med. 1997;103:368-375.
Sigterman TA, Krasznai AG, Snoeijs MG, Heijboer R, Schurink GW, Bouwman LH. Contrast Induced Nephropathy and Long-term Renal Decline After Percutaneous Transluminal Angioplasty for Symptomatic Peripheral Arterial Disease.Eur J Vasc Endovasc Surg. 2016;51:386-393.
Vuurmans T, Byrne J, Fretz E, Janssen C, Hilton JD, Klinke WP, Djurdjev O, Levin A. Chronic kidney injury in patients after cardiac catheterisation or percutaneous coronary intervention: a comparison of radial and femoral approaches (from the British Columbia Cardiac and Renal Registries).Heart. 2010;96:1538-1542.
Kronzon I, Saric M. Cholesterol embolization syndrome.Circulation. 2010;122:631-641.
Dizman N, Aydın Bahat K, Özkanlı Ş, Özkök A. Cholesterol embolization syndrome: A report of two cases.Turk Kardiyol Dern Ars. 2016;44:251-255.
Yücel AE, Kart-Köseoglu H, Demirhan B, Ozdemir FN. Cholesterol crystal embolization mimicking vasculitis: success with corticosteroid and cyclophosphamide therapy in two cases.Rheumatol Int. 2006;26:454-460.
Dizman N, Aydın Bahat K, Özkanlı Ş, Özkök A. Authors’ reply.Turk Kardiyol Dern Ars. 2016;44:538.
Feldkamp T, Baumgart D, Elsner M, Herget-Rosenthal S, Pietruck F, Erbel R, Philipp T, Kribben A. Nephrotoxicity of iso-osmolar versus low-osmolar contrast media is equal in low risk patients.Clin Nephrol. 2006;66:322-330.
Hardiek KJ, Katholi RE, Robbs RS, Katholi CE. Renal effects of contrast media in diabetic patients undergoing diagnostic or interventional coronary angiography.J Diabetes Complications. 2008;22:171-177.
Jo SH, Youn TJ, Koo BK, Park JS, Kang HJ, Cho YS, Chung WY, Joo GW, Chae IH, Choi DJ. Renal toxicity evaluation and comparison between visipaque (iodixanol) and hexabrix (ioxaglate) in patients with renal insufficiency undergoing coronary angiography: the RECOVER study: a randomized controlled trial.J Am Coll Cardiol. 2006;48:924-930.
Solomon RJ, Natarajan MK, Doucet S, Sharma SK, Staniloae CS, Katholi RE, Gelormini JL, Labinaz M, Moreyra AE; Investigators of the CARE Study. Cardiac Angiography in Renally Impaired Patients (CARE) study: a randomized double-blind trial of contrast-induced nephropathy in patients with chronic kidney disease.Circulation. 2007;115:3189-3196.
Rudnick MR, Davidson C, Laskey W, Stafford JL, Sherwin PF; VALOR Trial Investigators. Nephrotoxicity of iodixanol versus ioversol in patients with chronic kidney disease: the Visipaque Angiography/Interventions with Laboratory Outcomes in Renal Insufficiency (VALOR) Trial.Am Heart J. 2008;156:776-782.
Kuhn MJ, Chen N, Sahani DV, Reimer D, van Beek EJ, Heiken JP, So GJ. The PREDICT study: a randomized double-blind comparison of contrast-induced nephropathy after low- or isoosmolar contrast agent exposure.AJR Am J Roentgenol. 2008;191:151-157.
Thomsen HS, Morcos SK, Erley CM, Grazioli L, Bonomo L, Ni Z, Romano L; Investigators in the Abdominal Computed Tomography: IOMERON 400 Versus VISIPAQUE 320 Enhancement (ACTIVE) Study. The ACTIVE Trial: comparison of the effects on renal function of iomeprol-400 and iodixanol-320 in patients with chronic kidney disease undergoing abdominal computed tomography.Invest Radiol. 2008;43:170-178.
Nguyen SA, Suranyi P, Ravenel JG, Randall PK, Romano PB, Strom KA, Costello P, Schoepf UJ. Iso-osmolality versus low-osmolality iodinated contrast medium at intravenous contrast-enhanced CT: effect on kidney function.Radiology. 2008;248:97-105.
Wessely R, Koppara T, Bradaric C, Vorpahl M, Braun S, Schulz S, Mehilli J, Schömig A, Kastrati A; Contrast Media and Nephrotoxicity Following Coronary Revascularization by Angioplasty Trial Investigators. Choice of contrast medium in patients with impaired renal function undergoing percutaneous coronary intervention.Circ Cardiovasc Interv. 2009;2:430-437.
McCullough PA, Bertrand ME, Brinker JA, Stacul F. A meta-analysis of the renal safety of isosmolar iodixanol compared with low-osmolar contrast media.J Am Coll Cardiol. 2006;48:692-699.
From AM, Al Badarin FJ, McDonald FS, Bartholmai BJ, Cha SS, Rihal CS. Iodixanol versus low-osmolar contrast media for prevention of contrast induced nephropathy: meta-analysis of randomized, controlled trials.Circ Cardiovasc Interv. 2010;3:351-358.
Fishbane S. N-acetylcysteine in the prevention of contrast-induced nephropathy.Clin J Am Soc Nephrol. 2008;3:281-287.
Thiele H, Hildebrand L, Schirdewahn C, Eitel I, Adams V, Fuernau G, Erbs S, Linke A, Diederich KW, Nowak M. Impact of high-dose N-acetylcysteine versus placebo on contrast-induced nephropathy and myocardial reperfusion injury in unselected patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. The LIPSIA-N-ACC (Prospective, Single-Blind, Placebo-Controlled, Randomized Leipzig Immediate PercutaneouS Coronary Intervention Acute Myocardial Infarction N-ACC) Trial.J Am Coll Cardiol. 2010;55:2201-2209.
Thayssen P, Lassen JF, Jensen SE, Hansen KN, Hansen HS, Christiansen EH, Junker A, Ravkilde J, Thuesen L, Veien KT. Prevention of contrast-induced nephropathy with N-acetylcysteine or sodium bicarbonate in patients with ST-segment-myocardial infarction: a prospective, randomized, open-labeled trial.Circ Cardiovasc Interv. 2014;7:216-224.
Recio-Mayoral A, Chaparro M, Prado B, Cózar R, Méndez I, Banerjee D, Kaski JC, Cubero J, Cruz JM. The reno-protective effect of hydration with sodium bicarbonate plus N-acetylcysteine in patients undergoing emergency percutaneous coronary intervention: the RENO Study.J Am Coll Cardiol. 2007;49:1283-1288.
Tepel M, van der Giet M, Schwarzfeld C, Laufer U, Liermann D, Zidek W. Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine.N Engl J Med. 2000;343:180-184.
Zhang B, Liang L, Chen W, Liang C, Zhang S. The efficacy of sodium bicarbonate in preventing contrast-induced nephropathy in patients with pre-existing renal insufficiency: a meta-analysis.BMJ Open. 2015;5:e006989.
Huber W, Jeschke B, Page M, Weiss W, Salmhofer H, Schweigart U, Ilgmann K, Reichenberger J, Neu B, Classen M. Reduced incidence of radiocontrast-induced nephropathy in ICU patients under theophylline prophylaxis: a prospective comparison to series of patients at similar risk.Intensive Care Med. 2001;27:1200-1209.
Dai B, Liu Y, Fu L, Li Y, Zhang J, Mei C. Effect of theophylline on prevention of contrast-induced acute kidney injury: a meta-analysis of randomized controlled trials.Am J Kidney Dis. 2012;60:360-370.
Katholi RE, Taylor GJ, McCann WP, Woods WT, Womack KA, McCoy CD, Katholi CR, Moses HW, Mishkel GJ, Lucore CL. Nephrotoxicity from contrast media: attenuation with theophylline.Radiology. 1995;195:17-22.
Solomon R, Werner C, Mann D, D’Elia J, Silva P. Effects of saline, mannitol, and furosemide on acute decreases in renal function induced by radiocontrast agents.N Engl J Med. 1994;331:1416-1420.
Marenzi G, Ferrari C, Marana I, Assanelli E, De Metrio M, Teruzzi G, Veglia F, Fabbiocchi F, Montorsi P, Bartorelli AL. Prevention of contrast nephropathy by furosemide with matched hydration: the MYTHOS (Induced Diuresis With Matched Hydration Compared to Standard Hydration for Contrast Induced Nephropathy Prevention) trial.JACC Cardiovasc Interv. 2012;5:90-97.
Weinstein JM, Heyman S, Brezis M. Potential deleterious effect of furosemide in radiocontrast nephropathy.Nephron. 1992;62:413-415.
Spargias K, Alexopoulos E, Kyrzopoulos S, Iokovis P, Greenwood DC, Manginas A, Voudris V, Pavlides G, Buller CE, Kremastinos D. Ascorbic acid prevents contrast-mediated nephropathy in patients with renal dysfunction undergoing coronary angiography or intervention.Circulation. 2004;110:2837-2842.
Tasanarong A, Vohakiat A, Hutayanon P, Piyayotai D. New strategy of α- and γ-tocopherol to prevent contrast-induced acute kidney injury in chronic kidney disease patients undergoing elective coronary procedures.Nephrol Dial Transplant. 2013;28:337-344.
Toso A, Maioli M, Leoncini M, Gallopin M, Tedeschi D, Micheletti C, Manzone C, Amato M, Bellandi F. Usefulness of atorvastatin (80 mg) in prevention of contrast-induced nephropathy in patients with chronic renal disease.Am J Cardiol. 2010;105:288-292.
Patti G, Ricottini E, Nusca A, Colonna G, Pasceri V, D’Ambrosio A, Montinaro A, Di Sciascio G. Short-term, high-dose Atorvastatin pretreatment to prevent contrast-induced nephropathy in patients with acute coronary syndromes undergoing percutaneous coronary intervention (from the ARMYDA-CIN [atorvastatin for reduction of myocardial damage during angioplasty--contrast-induced nephropathy] trial.Am J Cardiol. 2011;108:1-7.
Jo SH, Koo BK, Park JS, Kang HJ, Cho YS, Kim YJ, Youn TJ, Chung WY, Chae IH, Choi DJ. Prevention of radiocontrast medium-induced nephropathy using short-term high-dose simvastatin in patients with renal insufficiency undergoing coronary angiography (PROMISS) trial--a randomized controlled study.Am Heart J. 2008;155:499.e1-499.e8.
Barbieri L, Verdoia M, Schaffer A, Nardin M, Marino P, De Luca G. The role of statins in the prevention of contrast induced nephropathy: a meta-analysis of 8 randomized trials.J Thromb Thrombolysis. 2014;38:493-502.
Quintavalle C, Fiore D, De Micco F, Visconti G, Focaccio A, Golia B, Ricciardelli B, Donnarumma E, Bianco A, Zabatta MA. Impact of a high loading dose of atorvastatin on contrast-induced acute kidney injury.Circulation. 2012;126:3008-3016.
Ludwig U, Riedel MK, Backes M, Imhof A, Muche R, Keller F. MESNA (sodium 2-mercaptoethanesulfonate) for prevention of contrast medium-induced nephrotoxicity - controlled trial.Clin Nephrol. 2011;75:302-308.
Bakris GL, Lass NA, Glock D. Renal hemodynamics in radiocontrast medium-induced renal dysfunction: A role for dopamine-1 receptors.Kidney Int. 1999;56:206-210.
Stone GW, McCullough PA, Tumlin JA, Lepor NE, Madyoon H, Murray P, Wang A, Chu AA, Schaer GL, Stevens M. Fenoldopam mesylate for the prevention of contrast-induced nephropathy: a randomized controlled trial.JAMA. 2003;290:2284-2291.
Bakris GL, Burnett JC. A role for calcium in radiocontrast-induced reductions in renal hemodynamics.Kidney Int. 1985;27:465-468.
Pflueger A, Larson TS, Nath KA, King BF, Gross JM, Knox FG. Role of adenosine in contrast media-induced acute renal failure in diabetes mellitus.Mayo Clin Proc. 2000;75:1275-1283.
Wang A, Holcslaw T, Bashore TM, Freed MI, Miller D, Rudnick MR, Szerlip H, Thames MD, Davidson CJ, Shusterman N. Exacerbation of radiocontrast nephrotoxicity by endothelin receptor antagonism.Kidney Int. 2000;57:1675-1680.
Kurnik BR, Allgren RL, Genter FC, Solomon RJ, Bates ER, Weisberg LS. Prospective study of atrial natriuretic peptide for the prevention of radiocontrast-induced nephropathy.Am J Kidney Dis. 1998;31:674-680.
Spargias K, Adreanides E, Demerouti E, Gkouziouta A, Manginas A, Pavlides G, Voudris V, Cokkinos DV. Iloprost prevents contrast-induced nephropathy in patients with renal dysfunction undergoing coronary angiography or intervention.Circulation. 2009;120:1793-1799.
Gurkowski L, MacDougall M, Wiegmann T. Effects of Misoprostol on Contrast-Induced Renal Dysfunction.Am J Ther. 1995;2:837-842.
Onbasili AO, Yeniceriglu Y, Agaoglu P, Karul A, Tekten T, Akar H, Discigil G. Trimetazidine in the prevention of contrast-induced nephropathy after coronary procedures.Heart. 2007;93:698-702.
Kolyada AY, Liangos O, Madias NE, Jaber BL. Protective effect of erythropoietin against radiocontrast-induced renal tubular epithelial cell injury.Am J Nephrol. 2008;28:203-209.
Yokomaku Y, Sugimoto T, Kume S, Araki S, Isshiki K, Chin-Kanasaki M, Sakaguchi M, Nitta N, Haneda M, Koya D. Asialoerythropoietin prevents contrast-induced nephropathy.J Am Soc Nephrol. 2008;19:321-328.
Toprak O, Cirit M, Tanrisev M, Yazici C, Canoz O, Sipahioglu M, Uzum A, Ersoy R, Sozmen EY. Preventive effect of nebivolol on contrast-induced nephropathy in rats.Nephrol Dial Transplant. 2008;23:853-859.
Markota D, Markota I, Starcevic B, Tomic M, Prskalo Z, Brizic I. Prevention of contrast-induced nephropathy with Na/K citrate.Eur Heart J. 2013;34:2362-2367.
Vogt B, Ferrari P, Schönholzer C, Marti HP, Mohaupt M, Wiederkehr M, Cereghetti C, Serra A, Huynh-Do U, Uehlinger D. Prophylactic hemodialysis after radiocontrast media in patients with renal insufficiency is potentially harmful.Am J Med. 2001;111:692-698.
Marenzi G, Marana I, Lauri G, Assanelli E, Grazi M, Campodonico J, Trabattoni D, Fabbiocchi F, Montorsi P, Bartorelli AL. The prevention of radiocontrast-agent-induced nephropathy by hemofiltration.N Engl J Med. 2003;349:1333-1340.