Pathophysiology Of Contrast-induced Nephropathy Research Articles

The Impact of Hydration and Other Strategies in prevention of Contrast-Induced Nephropathy

Introduction and purpose Contrast-induced nephropathy (CIN) remains a significant concern in clinical practice, particularly among patients undergoing contrast-enhanced imaging or interventional procedures. Characterized by an acute decline in renal function following exposure to contrast media, CIN not only poses substantial morbidity and mortality risks but also presents challenges in patient management and healthcare resource utilization. Despite extensive research efforts, the precise pathophysiology of CIN remains incompletely understood, with multifactorial mechanisms involving renal ischemia, oxidative stress, and direct tubular toxicity implicated in its development. This review explores the impact of hydration and other prophylactic strategies on the prevention of CIN. Numerous studies have demonstrated the effectiveness of various hydration protocols, including isotonic saline and bicarbonate solutions, in reducing the incidence of CIN. Additionally, the review evaluates the efficacy of pharmacological agents such as N-acetylcysteine, statins, and ascorbic acid, as well as emerging techniques like remote ischemic preconditioning.

Persistent/progressive subclinical contrast-induced nephropathy – predictors and effects of parenteral hydration. A prospective study in patients undergoing coronary angioplasty

Abstract Background In most cases, contrast-induced nephropathy (CIN) appears to be a transient event. The pathophysiology of CIN, which includes renal vasoconstriction and hypoxia, generation of cytotoxic reactive oxygen species, and even direct tubular toxicity, suggests however that the tubular impairment typical for CIN may not be entirely transient and that persistent/progressive subclinical kidney dysfunction could actually occur. Purpose We aimed to evaluate the incidence, identify the predictors, and assess the impact of parenteral hydration on the occurrence of persistent/progressive subclinical CIN in patients undergoing coronary angioplasty. Methods A total of 71 patients scheduled for elective coronary angioplasty were randomized into two groups: Control (n=36) and HYD (n=35). Patients in the HYD group received prophylactic hydration with saline solution (1 ml/kg/h; 6 h prior to and 12 h after the procedure). Plasma levels of neutrophil gelatinase-associated lipocalin (NGAL), a specific marker of tubular impairment, were evaluated prior to, and 48 h and 1 month after the angioplasty procedure. Persistent/progressive subclinical CIN at 1 month post-angioplasty was defined as a significant increase in NGAL at 48 h after the procedure that persisted (i.e., did not change by more than 10%) or aggravated (i.e., increased by more than 10%) at 1 month follow-up. The ability of several factors (i.e., age, hypertension, diabetes, use of nephrotoxic drugs, baseline creatinine clearance, volume of contrast agent) to predict persistent/progressive CIN was evaluated. The ability of parenteral hydration to prevent persistent/progressive CIN was also assessed. Results According to the current criteria, CIN was present in 5 (7.0%) patients. Meanwhile, subclinical CIN was identified in 36 (50.7%) patients, of which 10 (27.7%) presented persistent and 15 (41.6%) progressive CIN at 1 month follow-up. The volume of contrast administered during angioplasty was the only factor that differed significantly between patients who developed persistent/progressive CIN and those who did not (178±17 mL vs. 130±10 mL, p=0.01). In ROC analysis, contrast volume ≥150 mL predicted persistent/progressive CIN with 77% sensitivity and 60% specificity (p<0.001). Prophylactic hydration was associated with a 75% lower risk of persistent/progressive CIN (RR 0.25; 95% CI 0.09–0.65; p=0.001). Conclusions Despite the relatively low incidence of CIN, subclinical CIN was identified in more than 50% of the study patients. More than 2/3 of these patients presented persistent or progressive subclinical CIN at 1 month follow-up. The clinical impact of this persistent/progressive subclinical CIN in patients undergoing multiple contrast administrations remains to be established. Our data indicate that reducing the contrast volume and/or using prophylactic parenteral hydration can significantly reduce persistent/progressive subclinical CIN. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by a grant of the Romanian Ministry of Education and Research, CNCS-UEFISCDI

Preventing contrast-induced nephropathy (CIN) with herbal medicines: A review.

Currently, the use of iodinated contrast media in diagnostic imaging has been increased in clinical medicine. Contrast-induced nephropathy (CIN) is an important adverse effect of contrast media injection. According to the significant role of oxidative stress in the pathophysiology of CIN, different herbal antioxidants have been used for the prevention of nephropathy in different studies. In this review, we discussed the preventive effects of herbal medicine and natural products against CIN. We searched the electronic databases or search engines including PubMed, Scopus, ISI, Google Scholar with search terms such as "Contrast-induced nephropathy" and "Herbal medicine," "Contrast acute kidney injury" AND "natural products" and similar headings such as plant and extract. Known medicinal plants and active ingredients such as green tea, ginger, garlic, silymarin, curcumin, resveratrol, and thymoquinone have been examined for prophylactic effects or treatment of contrast media nephropathy. Herbal medicines have promising effects in the laboratory-based studies for the prevention and/or treatment of CIN. However, more practical and completed clinical trials are needed to investigate the clinical benefits of natural products against CIN.

The Role of MicroRNA in Contrast-Induced Nephropathy: A Scoping Review and Meta-Analysis.

Objective Early diagnosis of contrast-induced nephropathy (CIN) remains crucial for successful treatment; unfortunately, the widely used serum creatinine is elevated only in the late stage of CIN. The circulating microRNAs (miRNAs) are stable biomarker that might be useful. The aim of this scoping review and meta-analysis is to assess the role of miRNAs in CIN. Methods We performed a systematic literature search on topics that assess the role of miRNAs in CIN from several electronic databases. Results There were 6 preclinical studies and 2 of them validated their findings in human. Only miR-30a, miR-30c, miR-30e, and miR-188 have been validated in human models. Meta-analysis showed that increase in miR-30a expression was associated with higher incidence of CIN (OR 4.48 [1.52, 13.26], p = 0.007; I2: 94%, p < 0.001). An increase in miR-30e expression was associated with higher incidence of CIN (OR 2.34 [1.70, 3.20], p < 0.001; I2: 0%, p = 0.76). There is an indication that miR-188 is associated with contrast-induced apoptosis and might potentially be a drug target in the future. Conclusion This study highlighted the importance of certain miRNAs in CIN pathophysiology. Future researches should explore on the prognostic and therapeutic implication of miRNA in CIN.

Tert-Butylhydroquinone Treatment Alleviates Contrast-Induced Nephropathy in Rats by Activating the Nrf2/Sirt3/SOD2 Signaling Pathway.

Oxidative stress plays a critical role in the pathophysiology of contrast-induced nephropathy (CIN). Since the specific treatment of CIN remains an unmet medical need, it is imperative to find an effective strategy against the clinical management of CIN. The transcription factor Nrf2 is known to regulate antioxidative stress response. The aim of the present study was to assess the effects of tert-butylhydroquinone (t-BHQ), an activator of Nrf2, in the prevention of CIN and elucidate the underlying mechanism of its action in vitro and in vivo. We established a rat model of CIN and treated the animals with t-BHQ (25 mg/kg). The effects of t-BHQ treatment on CIN rats were elucidated by assessing renal function, HE staining, immunohistochemistry, and western blotting. We also studied the activity of oxidative stress-related markers, such as intracellular ROS level, MDA level, SOD2 activity, and GSH/GSSG ratio. We validated our results by siRNA-mediated silencing of Nrf2 in HK-2 cells exposed to the radiocontrast agent. Treatment with t-BHQ significantly ameliorated the renal function and the histopathological lesions in CIN rats. Further, pretreatment with t-BHQ significantly increased the SOD2 activity and GSH/GSSG ratio and decreased the levels of ROS and MDA in animals subjected to ioversol exposure. In addition, t-BHQ treatment increased the expression of Nrf2, Sirt3, and SOD2 and concomitantly decreased the expression of acetylated-SOD2. When Nrf2-silenced HK-2 cells were exposed to radiocontrast agent, they suffered severe cell oxidative stress, exhibited lower expression of Sirt3 and SOD2, and expressed higher levels of acetylated-SOD2; however, t-BHQ treatment did not affect the protein expression of these indicators in si-Nrf2 HK-2 cells. Our findings suggested that Nrf2 plays an important role in the regulation of the Sirt3/SOD2 antioxidative pathway, and t-BHQ may be a potential agent to ameliorate radiocontrast-induced nephropathy via activating the Nrf2/Sirt3/SOD2 signaling pathway in vitro and in vivo.

Is it possible to prevent contrast-induced nephropathy with dexpanthenol?

Contrast-induced nephropathy (CIN) is one of the side effects of diagnostic procedures. Oxidative stress plays an important role in CIN's pathophysiology. Dexpanthenol (Dexp) is a substance with antioxidant efficacy. We investigated the likely protective effects of dexpanthenol for CIN. Twenty-four Sprague-Dawley rats were divided randomly into four groups of 6 rats; control (group 1), Dexp (group 2), CIN (group 3) and Dexp + CIN (group 4). All rats were restricted of water moderately to facilitate of nephrotoxicity. Dexp was administered into the intraperitoneally at a dose of 500mg/kg for 5days in groups 2 and 4. The same amount of saline was applied via intraperitoneally to group 1 and 3. In CIN and Dexp + CIN groups, L-NAME (10mg/kg), tenoxicam (0.5mg/kg) and sodium amidotrizoate (10ml/kg) were administered on the 4th day via the tail vein for CIN. All rats were euthanized on the 6th day and samples for biochemical and pathological evaluations were collected. When the Dexp + CIN group and the CIN group were compared, it was found to be provide a significant decline at the level of acute tubular injury and necrosis in kidney biopsies by dexp. Furthermore Dexp significantly reduced the serum cystatin C (Cys-C) levels, not serum creatinine. There was no statistically significant difference between the groups in total oxidant and antioxidant levels. Dexpanthenol did not have significant effect on oxidative stress of acute kidney injury on this rat model. However, it has ameliorated serum Cys-C levels and histopathological findings of CIN.

Prevention of contrast-induced nephropathy by limb ischemic preconditioning: underlying mechanisms and clinical effects.

Contrast-induced nephropathy (CIN) is an important complication following diagnostic radiographic imaging and interventional therapy. It results from administration of intravascular iodinated contrast media (CM) and is currently the third most common cause of hospital-acquired acute kidney injury. CIN is associated with increased morbidity, prolonged hospitalization, and higher mortality. Although the importance of CIN is widely appreciated, and its occurrence can be mitigated by the use of pre- and posthydration protocols and low osmolar instead of high osmolar iodine-containing CM, specific prophylactic therapy is lacking. Remote ischemic preconditioning (RIPC), induced through short cycles of ischemia-reperfusion applied to the limb, is an intriguing new strategy that has been shown to reduce myocardial infarction size in patients undergoing emergency percutaneous coronary intervention. Furthermore, multiple proof-of-principle clinical studies have suggested benefit in several other ischemia-reperfusion syndromes, including stroke. Perhaps somewhat surprisingly, RIPC also is emerging as a promising strategy for CIN prevention. In this review, we discuss current clinical and experimental developments regarding the biology of CIN, concentrating on the pathophysiology of CIN, and cellular and molecular mechanisms by which limb ischemic preconditioning may confer renal protection in clinical and experimental models of CIN.

Evaluation of different sodium bicarbonate regimens for the prevention of contrast medium-induced nephropathy.

IntroductionThe rapid decline in renal function caused by radiographic contrast agents usually is transient, but it can result in chronic kidney disease. The pathophysiology of contrast-induced nephropathy (CIN) is poorly understood, but it may include acute hypoxia-induced oxidative stress and free radicals generated within the acid environment of the renal medulla. Thus, the alkalization of urine by sodium bicarbonate has been regarded as resulting in the reduction of CIN. The aim of this study was to determine whether a long-duration sodium bicarbonate regimen is more effective than a short-duration regimen in reducing CIN.MethodsOne hundred patients were assigned randomly to treatment with sodium bicarbonate solution using either the short regimen (intravenous bolus 3 mL/kg/h of 166 mEq/L sodium bicarbonate for 1 hour immediately before radiocontrast) or the long regimen (initial intravenous bolus of 3 mL/kg/h of 166 mEq/L sodium bicarbonate for 6 hr). Patients with renal dysfunction (estimated glomerular filtration rate [eGFR], 60 mL/min/1.73 m2 or less) who underwent elective or emergent coronary angiography (CAG) with/without percutaneous coronary intervention (PCI) at Nephrology Department (Theodor Bilharz Research Institute) were enrolled in the study. Data were analyzed by SPSS version 12, using Kruskal Wallis, ANOVA, Chi square test and Spearman rank correlation coefficient.ResultsThere was a significant increase in serum creatinine and a decrease in eGFR 48 hr post-intervention in group 1 (short regimen) with no statically difference regarding those parameters group 2 (long regimen). Serum potassium clearly was decreased significantly post procedure in both groups.ConclusionsThe results of our study indicated that the long regimen of bicarbonate supplementation was a more effective strategy to prevent CIN than the short regimen.

Physicochemical properties of radiographic contrast media, potential nephrotoxicity and prophylaxis.

Contrast induced nephropathy (CIN) remains a controversial topic. The clinical relevance of changes in laboratory parameters has been challenged; some authors have even suggested that CIN simply reflects natural fluctuations. Other areas of controversy include the pathophysiology of CIN, effectiveness of prophylactic approaches and differences in nephrotoxicity between individual contrast media (CM). The aim of this review is to summarize the current understanding of laboratory findings and explore its relationship to CM toxicity.

Reduction of Circulating Endothelial Progenitor Cell Level Is Associated with Contrast-Induced Nephropathy in Patients Undergoing Percutaneous Coronary and Peripheral Interventions

ObjectivesReduced number and impaired function of circulating endothelial progenitor cells (EPCs) in patients with chronic kidney disease have been reported. However, there is little data about the association between circulating EPC levels and risk of contrast-induced nephropathy (CIN). The aim of this study was to investigate the relationship between circulating EPCs and CIN in patients after angiography.Methods and ResultsA total of 77 consecutive patients undergoing elective percutaneous coronary intervention (PCI) and percutaneous transluminal angioplasty (PTA) were enrolled. Flow cytometry with quantification of EPC markers (defined as CD34+, CD34+KDR+, and CD34+KDR+CD133+) in peripheral blood samples was used to assess EPC number before the procedure. CIN was defined as an absolute increase ≧0.5 mg/dl or a relative increase ≧25% in the serum creatinine level at 48 hours after the procedure. Eighteen (24%) of the study subjects developed CIN. Circulating EPC levels were significantly lower in patients who developed CIN than in those without CIN (CD34+KDR+, 4.11±2.59 vs. 9.25±6.30 cells/105 events, P<0.001). The incidence of CIN was significantly greater in patients in the lowest EPC tertile (CD34+KDR+; from lowest to highest, 52%, 15%, and 4%, P<0.001). Using univariate logistic regression, circulating EPC number (CD34+KDR+) was a significant negative predictor for development of CIN (odds ratio 0.69, 95% CI 0.54–0.87, P = 0.002). Over a two-year follow-up, patients with CIN had a higher incidence of major adverse cardiovascular events including myocardial infarction, stroke, revascularization of treated vessels, and death (66.7% vs. 25.4%, P = 0.004) than did patients without CIN.ConclusionsDecreased EPC level is associated with a greater risk of CIN, which may explain part of the pathophysiology of CIN and the poor prognosis in CIN patients.

Contrast-induced nephropathy: pharmacology, pathophysiology and prevention

Modern iodinated contrast media (CM) consist of one or two tri-iodobenzene rings. They differ from each other in the composition of the side chains, creating different molecules and thus different brand substances. After intravascular administration, all CM are distributed rapidly into intravascular and extracellular fluids. They are eliminated solely by glomerular filtration. In patients with normal renal function, CMs are eliminated within 24 h. The pathophysiology of contrast-induced nephropathy (CIN) is based on three distinct but interacting mechanisms: medullary ischaemia, formation of reactive oxygen species and direct tubular cell toxicity. The contribution of each of these mechanisms to the development of CIN in the individual patient remains unclear. CIN prevention is extensively described in guidelines, such as the recently updated guideline from the Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR). The recent update is briefly discussed. Furthermore, it remains unclear if volume expansion with either NaCl 0.9 % or NaHCO3 1.4 % is superior. Teaching points • After intravascular injection, CM are distributed over intravascular and extracellular fluids.• CM are eliminated by glomerular filtration in patients with normal kidney function.• CIN pathophysiology is based on medullary ischaemia, formation of reactive oxygen species (ROS) and tubular cell toxicity.• It remains unclear if volume expansion with either NaCl 0.9 % or NaHCO31.4 % is superior.

The Lack of Benefit of a Combination of an Angiotensin Receptor Blocker and Calcium Channel Blocker on Contrast-Induced Nephropathy in Patients with Chronic Kidney Disease

Aim: Contrast-induced nephropathy (CIN) is a relatively common and serious complication, which occurs after the administration of contrast materials to patients. Although the pathophysiology of CIN is not exactly understood, ischemia of the medulla, oxidative stress, and direct toxicity of the contrast material are some of the factors that are implicated for the pathogenesis of CIN. To date, the only therapy that reduces the risk of CIN is volume expansion. There are conflicting results about the roles of angiotensin receptor blockers (ARB) and calcium channel blockers (CCB) in studies on CIN. For this reason the aim of this study was to compare the efficiency of the prophylactic use of amlodipine/valsartan plus hydration versus hydration only for the prevention of CIN in patients undergoing coronary angiography (CAG). Patients and methods: We prospectively enrolled 90 patients whose baseline serum creatinine levels were under 2.1 mg/dL and who were scheduled for CAG. Patients were divided into two groups. Group I (n = 45), consisted of patients who received amlodipine/valsartan plus hydration, group II (n = 45) consisted of patients who received only hydration. The patients in group I were given amlodipine/valsartan 5/160 mg once a day for a total of 3 days, starting one day before CAG and continuing on the day of and the day after the procedure. A 1 mL/kg/h sodium chloride infusion was administered for a total of 24 h, starting 12 h before the procedure and 12 h after, in all patients. The baseline serum creatinine (Scre) level was obtained before the procedure and repeated 48 h after. CIN was defined as an increase of ≥0.5 mg/dL or an increase of >25% in baseline Scre on the second day after CAG. Results: The baseline clinical characteristics of the treatment groups were similar. Baseline Scre was 1.13 ± 0.33 in group I and 1.07 ± 0.23 mg/dL in group II (p = 0.31). There was a significant difference between the Scre levels 48 h after CAG between the two groups (1.18 ± 0.33–1.05 ± 0.23) (p = 0.03). The reason for this was the increase of Scre in group I. CIN occurred in 17.8% (8/45) of patients in group I and in 6.7% (3/45) of patients in group II (p = 0.197). In the diabetic subgroup, CIN occurred in 10.5% (2/19) of patients taking amlodipine/valsartan and in none of the patients in group II (p = 0.486). The Mehran scores of the patients who developed CIN were significantly higher than those patients who did not develop CIN. Conclusion: Amlodipine/valsartan therapy plus hydration did not reduce the risk of CIN in chronic kidney disease (CKD) Stage 2 patients who underwent elective CAG using a low-osmolar nonionic contrast medium. This is because there was a decrease in the glomerular filtration rate (GFR) using the Levey Modification of Diet in Renal Disease (MDRD) formula in the amlodipine/valsartan group and CIN occurred at a higher frequency in this group; ARBs and CCBs may be withheld before CAG in high-risk patients.

Contrast-induced nephropathy in interventional cardiology.

Development of contrast-induced nephropathy (CIN), ie, a rise in serum creatinine by either ≥0.5 mg/dL or by ≥25% from baseline within the first 2–3 days after contrast administration, is strongly associated with both increased inhospital and late morbidity and mortality after invasive cardiac procedures. The prevention of CIN is critical if long-term outcomes are to be optimized after percutaneous coronary intervention. The prevalence of CIN in patients receiving contrast varies markedly (from <1% to 50%), depending on the presence of well characterized risk factors, the most important of which are baseline chronic renal insufficiency and diabetes mellitus. Other risk factors include advanced age, anemia, left ventricular dysfunction, dehydration, hypotension, renal transplant, low serum albumin, concomitant use of nephrotoxins, and the volume of contrast agent. The pathophysiology of CIN is likely to be multifactorial, including direct cytotoxicity, apoptosis, disturbances in intrarenal hemodynamics, and immune mechanisms. Few strategies have been shown to be effective to prevent CIN beyond hydration, the goal of which is to establish brisk diuresis prior to contrast administration, and to avoid hypotension. New strategies of controlled hydration and diuresis are promising. Studies are mixed on whether prophylactic oral N-acetylcysteine reduces the incidence of CIN, although its use is generally recommended, given its low cost and favorable side effect profile. Agents which have been shown to be ineffective or harmful, or for which data supporting routine use do not exist, include fenoldopam, theophylline, dopamine, calcium channel blockers, prostaglandin E1, atrial natriuretic peptide, statins, and angiotensin-converting enzyme inhibitors.

Preventing contrast-induced nephropathy part 1: What is CIN?

Contrast agents are widely used in cardiology as part of diagnostic and interventional procedures such as angiography and percutaneous coronary intervention. Despite their usefulness, these contrast agents are also known to be nephrotoxic, and damage to the kidneys can occur as a result of their use. Although the precise pathophysiology of contrast-induced nephropathy (CIN) remains unclear several risk factors have been identified that increase the likelihood of a patient developing it. This article, the first of two parts, outlines the general consensus on what puts a patient at risk of developing CIN.

Contrast‐induced Kidney Injury: Focus on Modifiable Risk Factors and Prophylactic Strategies

Contrast-induced nephropathy, also known as contrast-induced acute kidney injury, is associated with rapid and often irreversible decline in kidney function following the administration of iodinated contrast agents. Contrast-induced nephropathy is the third leading cause of acute kidney injury in hospitalized patients, and substantially increases mortality, morbidity, and length of hospitalization. Contrast-induced nephropathy follows a predictable time of onset and is potentially preventable. It has been the subject of numerous studies addressing characteristics of the populations at risk and prophylactic strategies. This evidence-based review summarizes recent literature and provides a nephrologists' perspective on contrast-induced nephropathy, focusing on: the pathophysiology of contrast-induced nephropathy; identification of populations at risk; correlation between contrast-induced nephropathy and the type of contrast agent used; and finally, measures to prevent contrast-induced nephropathy, including intravenous fluids, sodium bicarbonate, N-acetylcysteine, and hemofiltration/hemodialysis.

Prostaglandin-Based Renal Protection Against Contrast-Induced Acute Kidney Injury

It has been known for 3 decades that the kidneys rely considerably on a group of prostaglandins that are locally produced in both a constitutive and inducible fashion, primarily in the medulla, to regulate renal blood flow and a variety of functions in tubular cells that occupy that region of the kidney. Arachidonic acid released from phospholipids is converted by cyclooxygenase (COX-1 constitutively, COX-2 inducibly) in the kidney to PGI2, PGE2, PGF2, PGD2, and thromboxane A2. PGE2 and PGF2 are produced predominantly but not exclusively in the renal medulla, whereas degradative enzymes are present in both the cortex and medulla. Prostaglandins enter the tubular lumen by facilitated transport and are partially reabsorbed from the urine in the distal nephron, with urinary levels reflecting renal synthesis. In response to ischemia, vasoconstriction, norepinephrine, or angiotensin II, the kidney increases prostaglandin synthesis to modulate renal vascular resistance with a predominance of PGI2 and PGE2, which are vasodilatory, in contrast to PGF2 and thromboxane, which are vasoconstricting. 1 These actions may be more pronounced in patients with diabetes mellitus because both the endothelial isoform of nitric oxide synthase and the COX-1 and COX-2 enzymes lose their normal regulation in the outer medulla of diabetic rats. 2,3 In addition to these effects in diabetic patients, prostanoids appear to offset the vasoconstrictive effects of iodinated contrast agents. For example, Agmon and coworkers4 examined the effects of vasodilatory prostaglandins on outer medullary blood flow in a rat model of contrast nephropathy and demonstrated that the inhibition of prostanoid production more than doubled the number of necrotic tubules in the outer medulla. Prasad and colleagues 5 measured rat medullary blood flow in real time and demonstrated that prostanoids exert more vasodilatory effects than nitric oxide. These findings illustrate the importance of the prostanoids in maintaining outer medullary blood flow to the kidney. Moreover, these observations provide a physiological basis for the common recommendation that patients discontinue nonsteroidal antiinflammatory agents, which work above and beyond aspirin, before contrast exposure to impair constitutive (COX-1) and inducible (COX-2) production of prostaglandins. Article see p 1793

Contrast‐Induced Nephropathy: A Review Focusing on X‐ray and CT Applications and the Iso‐Osmolar Controversy

SummaryAfter administration of contrast media the incidence of acute renal failure requiring dialysis is low. Clinical studies on contrast‐induced nephropathy (CIN) therefore use a relative or absolute increase in serum creatinine as a surrogate marker. However, there is no generally accepted threshold for increases in creatinine. The lack of consistency in the definition of CIN makes it difficult to compare trials. The serum creatinine level is also only a poor marker of renal function. Increases in serum creatinine after contrast examination are associated with increased mortality, morbidity and longer hospital stays. However, such correlations have been shown only for coronary interventions. Not all cases of renal failure following cardiac angiography are necessarily related to the contrast medium, as in these patients there are several other reasons for loss of renal function. There are no studies showing a correlation between patient outcome and CIN after intravenous administration of contrast media. While the pathophysiology of CIN is not yet completely understood, it most certainly involves the interplay of multiple factors. It is highly likely that direct tubular toxicity of the CM contributes to the aetiology, whereas the role of the physicochemical properties of CM may have been over‐interpreted. There is an ongoing controversy as to whether the iso‐osmolar CM iodixanol is better tolerated by the kidneys than low‐osmolar CM (LOCM). Some randomized trials have demonstrated benefits of this substance. However, to date meta‐analyses and registry studies have not shown a consistent picture. In the last few months some randomized trials have been published which have not found an advantage of iodixanol over LOMC, whether administered intra‐arterially or intravenously.

Pathophysiology of Contrast-Induced Nephropathy

Contrast-induced nephropathy (CIN) is the third leading cause of acute kidney injury in hospitalized patients and is associated with significant patient morbidity. The pathogenesis of CIN is complex and not fully understood, but iodinated contrast agents induce intense and prolonged vasoconstriction at the corticomedullary junction of the kidney. Moreover, high-osmolar dyes directly impair the autoregulatory capacity of the kidney through a loss of nitric oxide production. These effects, coupled with direct tubular toxicity of contrast media, lead to overt acute tubular necrosis and the syndrome of CIN.