British Journal of Anaesthesia

BJA Advance Access originally published online on August 6, 2007
British Journal of Anaesthesia 2007 99(4):474-483; doi:10.1093/bja/aem237

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Contrast-induced nephropathy

G. T. C. Wong and M. G. Irwin^*

Department of Anaesthesiology, The University of Hong Kong, Room 424, Block K, Queen Mary Hospital, Pokfulam Road, Hong Kong

^* Corresponding author. E-mail: mgirwin{at}hkucc.hku.hk

	Abstract

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Interventional radiological procedures involving anaesthesia are generally increasing. Contrast-induced nephropathy (CIN), usually defined as an increase in serum creatinine of 44 µmol litre^–1 (0.5 mg dl^–1) or a 25% increase from the baseline value 48 h after intravascular injection of contrast media, is a common and potentially serious complication of the use of iodinated contrast media in patients at risk of acute renal injury. It is an important cause of hospital-acquired renal failure, may be a difficult differential diagnosis and the incidence does not appear to have changed over the last few decades. In the general population, the incidence of CIN is estimated to be 1–2%. However, the risk for developing CIN may be as high as 50% in some patient subgroups, such as those with diabetes mellitus and pre-existing renal impairment. The impact of CIN on clinical outcomes has been evaluated most extensively in patients undergoing percutaneous coronary intervention where it is associated with increased mortality both in hospital and at 1 yr. As treatment is limited to supportive measures while awaiting the resolution of the renal impairment, emphasis needs to be directed at prevention.

Keywords: complications, renal; fluids, i.v.; heart, coronary occlusion; imaging; kidney, failure

	Introduction

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Contrast-induced nephropathy (CIN) is a well-documented phenomenon and now ranks third in the causes of hospital-acquired acute renal failure in the USA.^{19 77} Diagnostic and therapeutic procedures requiring the use of i.v. contrast are increasing with many of these procedures being developed as alternatives to open surgery in elderly patients and those with significant co-morbidities. An estimated 75 million doses of contrast are administered yearly.¹⁸ Many of these procedures such as endovascular stenting and peripheral angioplasty are performed in operating theatres and may require general/regional anaesthesia or sedation and analgesia for successful completion. Patients may also present to the operating theatre for their definitive surgical treatment shortly after exposure to high doses of i.v. contrast, for example, semi-emergency coronary artery surgery. Inevitably, anaesthetists are becoming more involved with the care of these individuals. Although CIN is a reasonably well-recognized and reviewed topic within the radiology and cardiology literature, the focus has been on patients in the ambulatory setting. The purpose of this article is primarily to alert the anaesthetist to the possibility of perioperative CIN in surgical patients. An overview of the current understanding of this condition, its pathophysiology, and some of the preventative measures that have been investigated will be provided. Some perioperative strategies will be proposed which may benefit these patients. Considering that the stress of surgery, disturbances of fluid balance, perioperative fasting, and administration of anaesthesia can adversely affect renal function, as perioperative physicians, anaesthetists could play a pivotal role in minimizing renal damage in this group of patients.

	Definition

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CIN is implied when there is a temporal link between deterioration of renal function and the administration of i.v. contrast, in the absence of any other aetiology. The widely quoted definition requires an absolute increase in serum creatinine of 44 µmol litre^–1 or a relative increase of 25% from baseline.^{10 71}

Incidence of CIN
Quoted figures are likely to underestimate the true extent of the problem given that serum creatinine inherently has limited sensitivity in detecting renal dysfunction and earlier studies used a more conservative criterion. However, for those without pre-existing renal impairment, figures range from 3.3% to 8%,^{10 94} and increases to 12–26% for those with renal disease or diabetes mellitus.³³ The impairment tends to be non-oliguric and transient, with the peak serum creatinine usually occurring around day 3 and returning to normal in the majority of cases within 2 weeks.¹²² Some patients may develop more severe renal failure, with approximately 1% of this group requiring dialysis. Although small in number, the morbidity and mortality rates in this group are alarmingly high, with an in-hospital mortality rate of up to 30% and an 80% 2 yr mortality rate.^{34 67}

The large discrepancy in the documented incidence of CIN is probably related to the variation in definitions, type and volume of contrast used, employment of any preventative measures, diverse combinations of patient risk factors, and, most importantly, what actually constitutes pre-existing renal impairment. Although small in relative terms, the absolute number of patients affected is not when considering the number of doses of contrast administered per annum.

Risk factors
Factors that have been identified to be associated with the development of CIN include: pre-existing renal impairment, diabetes mellitus, advanced age, peri-procedural intravascular depletion, congestive heart failure, volume and type of contrast administered, and concomitant use of other nephrotoxic drugs.^{67 68 94} The proportional contribution of any one factor to the development of CIN has not been specifically investigated. However, attempts have been made to further stratify patients by assigning a weighting to each of the risk factors, resulting in the development of risk scores for those undergoing coronary angiography.⁶⁸

A recent prospective analysis of 6773 patients undergoing coronary angiography revealed that both a low baseline haematocrit and a peri-procedural drop in haematocrit regardless of baseline were independent risk factors. Patients were analysed in quintiles of haematocrit level, with those below a level of 36.8% having the greatest incidence of CIN. Each further 3% decrease in haematocrit increased the odds of CIN by 30% or 26%, respectively, in those with or without baseline renal impairment.⁸⁰

Pharmacology of contrast
Commercially available media are all tri-iodinated benzene derivatives and are classified according to their ionization, osmolarity, and structure. Ionic contrast media dissociate in water whereas their non-ionic counterparts do not, despite being water-soluble. The ratio of iodine to dissolved particles describes an important relationship between opacification and osmotoxicity of the agent, with higher ratios being more desirable. Agents have been classified into high-osmolar (ratio = 1.5), low osmolar (ratio = 3.0), and isotonic agents (ratio 6.0). In the 1990s, agents with dimeric molecules containing two benzene rings were produced, which possessed the desirable qualities of no ionicity, low osmolarity combined with increased iodine atoms per molecule, and greater water solubility, but they were of a higher viscosity compared with their monomeric predecessors. The increased viscosity, in turn, could potentially affect renal blood flow and tubular urine flow.⁵¹ However, initial studies point to a lower incidence of CIN with the use of isotonic dimeric agents in high-risk patients.^{4 17}

The kinetics of distribution of all contrast media is similar, with low lipophilicity, low plasma protein binding, and minimal biotransformation. The contrast particles quickly equilibrate across capillary membranes after i.v. injection, except in the brain with an intact blood–brain barrier.⁹⁰ They tend to remain extracellular with the exception of proximal renal tubular cells.⁴⁷ Movement of particles back into the circulation occurs, resulting in a bi-exponential decay in plasma iodine levels,⁷³ with an elimination half-time of about 2 h. Nearly, all the injected substance is cleared by the kidneys and excreted in the urine unchanged in those with normal renal function. However, hepatic metabolism, enterohepatic circulation, and biliary elimination are increased in those with renal impairment.¹⁴ Contrast molecules are easily removed by dialysis as there is little protein binding.

Renal handling of contrast media
Contrast medium molecules are freely filtered and the concentration in the ultrafiltrate initially approaches that of plasma. As the filtrate proceeds along the tubules, variable amounts of water are reabsorbed, resulting in concentrations that can be 50–100 times that of plasma.¹¹³ There is a very small amount of contrast media uptake into the proximal tubular cells where it forms conspicuous vacuoles, which may be detectable up to 28 days after administration.²³ Like other osmotic particles, contrast molecules in the tubular lumen reduce overall water reabsorption, leading, therefore, to an increase in intraluminal pressure and a decrease in the gradient for filtration from glomerular capillaries. This increase in sodium and water delivery to the distal portion of the tubules activates the ‘tubuloglomerular feedback’ mechanism that reduces the glomerular filtration rate (GFR) of the whole kidney. The raised renal interstitial pressure may contribute to the reduced GFR^{118 119} and probably to renal medullary hypoxia by local compression of vasa recta.⁸⁸

Pathophysiology of CIN
Although the pathogenesis of this condition is not fully understood, it is most likely the result of the prolonged vasoconstriction and impaired autoregulation induced by contrast media predisposing to medullary hypoxia, in combination with direct cytotoxicity (Table 1).¹¹⁷ This may be further influenced by contributions from several systemic factors. Therefore, an appreciation of the factors affecting renal microcirculatory haemodynamics is pivotal to understanding the pathogenesis of CIN and the expected response to preventive measures. The reader is referred to reviews in this area for a more thorough understanding of the intricacy of this complex circulatory system under normal circumstances.^{25 84} A brief overview of some of the factors governing the intrarenal haemodynamic balance will be presented focusing on those factors germane to understanding CIN.

View this table: [in this window] [in a new window]   Table 1 Factors implicated in the pathogenesis of CIN

 
The renal circulation is subjected to autoregulation which typically refers to maintenance of a constant total renal flow within a range of arterial perfusion pressure. However, there may be regional cortico-medullary differences in the extent to which autoregulation occurs resulting from the net effect of the many neural, hormonal, paracrine, and autocrine influences. Medullary autoregulation may be, in part, dependent on extracellular hydration status, where volume expansion may impair autoregulatory mechanisms.⁶⁶ Evidence suggests nitric oxide (NO) has a key role in renal autoregulation through its vasodilatory effects and inhibition of NO production would interfere with this process.⁴⁸ Vasopressin can cause vasoconstriction via V₁ receptors predominantly in the medulla.⁷⁵ The renal medulla is predisposed to low oxygen tension, resulting in the release of adenosine. This product of adenosine triphosphate metabolism is produced, among other places, in various microvascular beds in response to ischaemia. It produces vasodilatation via low affinity A₂ receptor activation which may increase blood flow within the medulla.¹⁰¹ However, it is a potent vasoconstrictor when it activates the high affinity A₁ receptors reducing cortical and net renal blood flow.⁸⁹ Angiotensin II provides constriction of the juxtamedullary microcirculation.⁸³ Prostaglandins cause redistribution of blood flow from the superficial to the juxtamedullary cortex and are found in abundance in the renal medulla.^{46 59} Endothelins are endogenous peptides that are potent vasoconstrictors,⁵⁷ and can cause decreases in renal blood flow and GFR, and constrict outer medullary descending vasa recta, thus predisposing the renal medulla to ischaemia.¹²

Therefore, it would seem that microcirculatory tone is regulated by the interplay of various influences that mediate vasoconstriction and vasodilatation. As a primary role of the kidney is to maintain volume, the balance of the vasculature tends towards a constrictive state in the presence of hypovolaemia. Unrecognized hypovolaemia often exists in patients undergoing contrast studies for a variety of reasons, including debilitation from underlying medical disease, repeated fasting, and third space fluid losses from surgical procedures. Contrast media administration results in diminution of renal blood flow, contributing to the decrease in glomerular filtration and ischaemia in the medulla, an area with a high metabolic requirement and remote from its blood supply. This added vasoconstrictive response occurring in an already contracted renal vasculature may be responsible for the development of renal dysfunction in CIN.

Contrast media-induced vasoconstriction may be a result of a direct effect on vascular smooth muscle,⁵⁰ changes in calcium physiology,⁹ or from a local increase in adenosine⁸⁹ and endothelin⁶ production. In the canine model, contrast media initially cause vasodilatation, followed by prolonged vasoconstriction.⁹ It has also been shown to cause dose-dependent, reversible contractions in human, rabbit, and dog, but not in pig renal arteries.⁹¹ There may also be regional differences in the vascular response to contrast media, with a greater reduction in flow to the outer medulla.⁸¹ In animals, the diminution of renal blood flow may also be a consequence of impaired vasodilation secondary to impaired NO production. NO production is reduced in rat renal artery smooth muscle cells exposed to radiographic contrast,⁹² and a decreased NO level is associated with a concomitant reduction in medullary blood flow in the rat.² Finally, contrast media can increase intrarenal pressure and thus diminish renal blood flow from physical compression, an observation which correlates with the osmolarity of the agent.⁵²

In addition to the disturbance in renal haemodynamics with resultant regional hypoxia, other mechanisms contribute to the development of this condition. These include direct toxic effects on renal tubules by the contrast,⁴⁰ changes in blood rheology, generation of reactive oxygen species (ROS),⁸⁸ and possibly a low haematocrit.⁸⁰

CIN is primarily a tubular disorder,^{13 15} and the direct toxic effects of contrast media on cells have mainly been performed in cell lines displaying tubular phenotypes.³⁶ Observed effects on cells included cellular energy failure, a disruption of calcium homeostasis,⁴⁴ a disturbance of tubular cell polarity,³⁷ and apoptosis.^{11 43}

Viscosity of blood flowing through the vasa recta is usually kept low to counteract the high resistance in these vessels. Contrast media have complex effects on blood rheology, including an increase in whole blood viscosity, a decrease in haematocrit, and a reduction in red cell deformability, producing an increased resistance to flow.⁸⁸

ROS are endogenously produced particles that can function as extracellular signalling molecules and may be involved in the actions of vasoconstrictors.^{22 97 99} Oxidative stress occurs when the amount of ROS exceeds the levels of antioxidants. This is thought to be increased in chronic renal failure⁶⁵ and diabetes,⁹⁸ known risk factors for CIN. Some studies examining the use of antioxidants in attenuating CIN have yielded positive results (discussed later). As such, ROS has been implicated in the pathogenesis of CIN.⁸⁷

	Prophylactic measures

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Hydration
Solomon and colleagues¹⁰² demonstrated the benefits of hypotonic (0.45%) saline pre-hydration in reducing the risk of CIN in a group of patients with pre-existing renal insufficiency (Table 2). In that trial, the use of fluids alone was superior to fluids plus mannitol or furosemide. The observation that forced diuresis with furosemide and mannitol were no better than hydration alone was also demonstrated in the PRINCE study.¹⁰⁷ Indeed, the use of loop diuretics may actually exacerbate post-procedural renal function.¹²⁰ Normal saline has also been shown to be better than 0.45% saline, especially in women, diabetics, and patients receiving 250 ml or more of contrast.⁷⁴ The authors proposed that the sodium load is crucial for the protective effect as it enables more effective volume expansion and inhibition of rennin–angiotensin activity. A recent small prospective trial demonstrated that infusion of isotonic sodium bicarbonate was associated with a smaller increase in serum creatinine compared with isotonic saline, suggesting a benefit from alkalinization of the urine.⁶⁹ Evidence comparing i.v. and oral hydration is inconclusive.^{112 116} However, hydration appears more beneficial if the fluid load is given before the procedure.⁵ There are currently no studies of the optimal rate of pre-hydration, but most of the studies used a rate of 1–2 ml kg^–1 h^–1, for 6–12 h before the procedure. There have been no reported complications from pre-hydration.

View this table: [in this window] [in a new window]   Table 2 Summary of prophylactic measures

 
Diuretics
As mentioned earlier, diuretics and mannitol have no beneficial effects and may be harmful^{102 107 123} and their use cannot be recommended for CIN prophylaxis.²⁸

Antioxidants
N-Acetylcysteine is the acetylated form of the amino acid L-cysteine and has long been established clinically as a mucolytic and as a treatment for acetaminophen overdose. Being an abundant source of sulfhydryl groups, its metabolites are able to act as free radical scavengers.⁵³ This antioxidant property combined with a vasodilatory effect on the renal medullary circulation^{29 41} has led to studies evaluating its effects on CIN. Owing to differences in patient selection, radiological procedures, dosages, type and volume of contrasts used, these trials have yielded inconsistent results. Although recent meta-analyses^{7 24 58 62 76 85} have shown that N-acetylcysteine significantly reduced the incidence of CIN, particularly when used with pre-hydration, a number of the authors have cautioned against recommending N-acetylcysteine as universal prophylaxis before results from larger quality trials are available. Endovascular aortic aneurysm repair (EVAR) causes significant acute renal injury in most patients and a recent trial suggests that this is not attenuated by N-acetylcysteine.⁷⁰

A single trial has demonstrated significant beneficial effects from the use of another antioxidant, ascorbic acid, in patients with renal insufficiency undergoing coronary angiography.¹⁰⁴ Although promising, further trials are required to validate these results.

Drugs acting on the renal circulation
Dopamine and fenoldopam
Studies of dopamine in the prevention of CIN are conflicting and most fail to show any benefit and undesirable side-effects such as tachycardia.^{31 38 49 124} Fenoldopam mesylate is a selective dopamine₁ receptor agonist with no ₁ or ß₁ effects and only mild ₂ antagonism.⁷⁹ Despite having favourable effects on renal haemodynamics, it failed to reduce the incidence of CIN.¹⁰⁸

Calcium channel antagonists
Calcium channel antagonists have potential to prevent the adverse renal haemodynamic changes from hyperosmolar contrast media.⁹⁶ However, only one small trial demonstrated any value with their use,⁷⁸ whereas other studies showed no beneficial effects.^{55 103}

Adenosine antagonists
Adenosine has a prominent role in the tubuloglomerular feedback mechanism^{16 82 86 111} and has been implicated in the pathogenesis of CIN.⁸⁹ However, meta-analysis of clinical studies involving theophylline again showed heterogeneity of results, overall indicating a trend but no significant benefit of CIN.⁸ Aminophylline did not demonstrate any benefit.^{1 100}

Statins
Statins (hydroxymethylglutaryl co-enzyme A reductase inhibitors) have ‘pleiotropic effects’⁴⁵ which encompass modification of endothelial function, plaque stability, thrombus formation, and inflammatory pathways. Preoperative statin therapy has been reported to be associated with improved postoperative outcomes.⁴² Retrospective analysis demonstrated an association with a reduction in CIN in patients undergoing percutaneous coronary interventions.⁵⁴ Although side-effects are rare, larger prospective trials are required to delineate its role as prophylaxis for CIN. However, it is worth considering for patients who may gain from other beneficial effects of statins.

	Physical measures

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Prophylactic haemofiltration
Prophylactic haemofiltration in an ICU setting reduced the incidence of CIN, in hospital and cumulative 1 yr mortality in chronic renal failure patients undergoing coronary angiography when compared with hydration alone.⁶⁴ However it is invasive, inconvenient, labour, and equipment intensive, may only be cost-effective under very limited circumstances⁵⁶ and cannot be universally applied to all high-risk patients.

Haemodialysis
A number of studies have examined the effect of immediate post-procedural haemodialysis on the incidence of CIN in patients with chronic renal failure.^{61 106 121} Although small in patient numbers, none of the studies has shown any benefits.

Given the number of proposed mechanisms for the genesis of CIN, it is not surprising that the multiple prophylactic measures that have been tried have produced equivocal or negative results. This may also reflect the quality of the studies, which are frequently small and, thus, underpowered and poorly designed. It is also not surprising that hydration is efficacious and diuresis is not. Normovolaemia can probably best influence the overall balance of renal haemodynamics by, among others, preventing the activation of tubuloglomerular feedback and of the rennin–angiotensin system. In contrast, the various other drugs target only a component of the control of renal blood flow and, therefore, are not sufficiently effective in swinging the balance.

	Peri-procedural management

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Identifying those at risk
The anaesthetist should be aware of patients who will receive contrast media as part of their operative procedure and those who have received contrast within the previous 10 days. Identifying those with risk factors for CIN should be helpful. Certain patient subgroups may be prone to develop perioperative renal dysfunction independent of the use of contrast agents, for example, those with sepsis. Even small decrements in renal function in these susceptible individuals could potentially increase morbidity and length of hospital stay. Recognition of CIN, along with identifying the patients at risk, is the first step towards minimizing the harm from contrast.

Serum creatinine has been the traditional marker to screen for baseline renal dysfunction but other factors such as age, gender, body mass, and ethnicity can also influence its level. Determination of GFR provides more accurate information, but it is cumbersome and expensive to measure and is not feasible for all patients undergoing radiological procedures. Estimation of GFR using equations such as the Cockcroft and Gault formula or the Modification of Diet in Renal Disease Study equation may be more useful clinically as they may identify mild to moderate decreases in GFR in patients with ‘normal’ creatinine levels. It would also help to stage the degree of renal impairment. Serum Cystatin C is a protein which is secreted by virtually all nucleated cells. It is not subject to the same confounding factors as creatinine and may be more sensitive in detecting reductions in GFR. There is evidence that Cystatin C increases earlier after contrast administration compared with serum creatinine, and therefore is potentially useful in early detection of CIN, especially in patients with short periods of hospitalization.⁹³

Evaluation of fluid status
It is vitally important that hypovolaemia be avoided in those undergoing contrast studies. Review of the patient’s history may reveal events such as repeated nil by mouth orders or reduced fluid intake that would predispose the patient to develop dehydration. It is difficult to establish clear, objective, clinically useful end-points for optimal hydration that are universally applicable. Short of invasive monitoring, clinical indicators such as normal heart rate, normotension with warm peripheries, and adequate urine output must be used. Right heart catherization should be considered for haemodynamic monitoring in patients with uncompensated heart failure.¹⁰⁵

Drug–contrast media interactions
The patient’s preoperative drugs should be checked to avoid potentially nephrotoxic drugs if possible. It is more difficult to determine which drug may be potentially harmful in patients awaiting contrast administration. An illustrative example is the use of angiotensin-converting enzyme inhibitors (ACEI). Contrast agents are known to inhibit ACE.⁶⁰ ACEI and diabetes mellitus have been shown to be associated with CIN in a trial where patients were infused with a specially prepared solution containing half-normal sodium chloride, mannitol, NaHCO₃, and furosemide at 100 ml h^–1 from 1 h before to 2 h after the procedure.⁶³ The increased risk of developing CIN with the use of captopril was also demonstrated in a small randomized controlled trial (RCT) of patients undergoing coronary angiography.¹¹⁵ In contrast, a small-randomized trial comparing the use of N-acetylcysteine, fenoldopam, and normal saline, the risk of developing CIN was not associated with concomitant use of an ACEI.³ However, the same trial also failed to show any association with diabetes mellitus, a known risk factor for CIN. Another RCT demonstrated some protective effect with ACEI in diabetic patients.³⁵ In this trial, there was a rather high rate of rise in post-procedural creatinine of 29%. On balance, there is insufficient evidence to support ACEI use as prophylaxis in CIN. However, there is little evidence supporting its omission in those who are stable on therapy.

Members of the Contrast Media Safety Committee of the European Society of Urogenital Radiology have produced a summary document on interactions between contrast media and other drugs.⁷² Of particular concern is the decreased renal clearance of drugs such as metformin, with the potential to cause lactic acidosis. Patients receiving beta-blockers are more likely to develop anaphylactoid reactions to iodinated contrast, and are potentially more resistant to treatment.

Concomitant consumption of nephrotoxic drugs such as aminoglycosides and non-steroidal anti-inflammatory drugs (NSAID) can potentiate CIN. The adverse effects of NSAIDs on renal function in susceptible individuals are well documented.¹²⁵ It appears that COX-2 selective inhibitors offer no advantage over traditional NSAID in terms of nephrotoxicity.³⁰ Although no specific trials have examined this issue, substitution of these medications with other forms of analgesics during the peri-procedural period is recommended.²⁸ Other nephrotoxic drugs must be used with caution, especially those requiring therapeutic level monitoring such as aminoglycosides and vancomycin. Concentrations of other drugs reliant on renal clearance, such as digoxin, may also be affected. Close monitoring of renal function, with drug level monitoring and possible dose adjustment, may be warranted.

Caution must also be exercised with the use of diuretics, as they may enhance the contrast-induced diuresis, which some claim contribute to renal toxicity.

Anaesthetic technique
At present, there are no data available suggesting that inhalation, i.v. or regional anaesthesia, significantly influence the development or severity of CIN. However, the anaesthetist should ensure that the patient is well hydrated before induction and avoid the indiscriminate use of vasopressors to support arterial pressure before fluid status is optimized. Both volatile agents and neuroaxial blockade cause systemic vasodilatation, which if left uncorrected, may affect renal perfusion. However, provided mean arterial pressure is adequate, epidural blockade does not significantly alter renal blood flow.¹¹⁰ Although there appears to be no significant differences in the measured postoperative creatinine levels when the different volatile agents are compared,^{20 32 109} there is some weak evidence that prolonged sevoflurane exposure is associated with transient glomerular and tubular injury.^{26 39} It has to be emphasized that these studies involved comparing sevoflurane with desflurane and isoflurane, respectively, and were performed in patients not receiving contrast media. The EUROSTAR data indicate that patients appeared to benefit when a local anaesthetic technique was used for EVAR in treating infrarenal aneurysms of the abdominal aorta, although renal function was not a specific outcome measure.⁹⁵

Alternative to iodinated contrast
Although gadolinium-based contrast agents in doses of up to 0.3 mmol kg^–1 are considered to be non-nephrotoxic, renal dysfunction can occur after its administration in these doses, especially in patients with diabetic nephropathy or pre-existing renal impairment.^{27 114} Currently, it is only approved for use in magnetic resonance imaging contrast studies, but it has been suggested and used as an alternative to iodinated agents for radiographic contrast studies. However, after review of current available evidence, both the CIN Consensus Working Panel and the Contrast Media Safety Committee of the European Society of Urogenital Radiology cannot recommend the use of this class of agents to avoid nephrotoxicity.^{21 27}

	Conclusions

Top Abstract Introduction Definition Prophylactic measures Physical measures Peri-procedural management Conclusions References

 
CIN is a complex clinical disorder that may affect increasing number of patients in the perioperative period. It is unlikely that any single therapeutic intervention can prevent this problem apart from choosing a viable alternative imaging modality. The anaesthetist should be aware of the disorder, identify those patients at risk, and perform preoperative assessment with a focus on volume status, identifying and withholding potentially nephrotoxic agents and drugs that may accumulate with reduced renal function. The patient should be kept normovolaemic at the time of contrast exposure and a low haematocrit avoided. For high-risk patients, prophylaxis with N-acetylcysteine should be considered and the operator should be reminded to use the minimal amount of contrast necessary. Sevoflurane may be avoided for general anaesthesia in prolonged procedures where there is a viable alternative and local anaesthesia used where appropriate. At risk patients should be adequately followed-up with renal function testing and maintenance of post-procedure hydration.

	References

Top Abstract Introduction Definition Prophylactic measures Physical measures Peri-procedural management Conclusions References

 
1 Abizaid AS, Clark CE, Mintz GS, et al. Effects of dopamine and aminophylline on contrast-induced acute renal failure after coronary angioplasty in patients with preexisting renal insufficiency. Am J Cardiol (1999) 83:260–3.[CrossRef][Web of Science][Medline]

2 Agmon Y, Peleg H, Greenfeld Z, Rosen S, Brezis M. Nitric oxide and prostanoids protect the renal outer medulla from radiocontrast toxicity in the rat. J Clin Invest (1994) 94:1069–75.[Web of Science][Medline]

3 Allaqaband S, Tumuluri R, Malik AM, et al. Prospective randomized study of N-acetylcysteine, fenoldopam, and saline for prevention of radiocontrast-induced nephropathy [see comment]. Catheter Cardiovasc Interv (2002) 57:279–83.[CrossRef][Web of Science][Medline]

4 Aspelin P, Aubry P, Fransson SG, et al. Nephrotoxic effects in high-risk patients undergoing angiography [see comment]. N Engl J Med (2003) 348:491–9.[Abstract/Free Full Text]

5 Bader BD, Berger ED, Heede MB, et al. What is the best hydration regimen to prevent contrast media-induced nephrotoxicity? Clin Nephrol (2004) 62:1–7.[Web of Science][Medline]

6 Bagnis C, Idee JM, Dubois M, et al. Role of endothelium-derived nitric oxide-endothelin balance in contrast medium-induced acute renal vasoconstriction in dogs. Acad Radiol (1997) 4:343–8.[CrossRef][Web of Science][Medline]

7 Bagshaw SM, Ghali WA. Acetylcysteine for prevention of contrast-induced nephropathy after intravascular angiography: a systematic review and meta-analysis. BMC Med (2004) 2:38.[CrossRef][Medline]

8 Bagshaw SM, Ghali WA. Theophylline for prevention of contrast-induced nephropathy: a systematic review and meta-analysis. Arch Intern Med (2005) 165:1087–93.[Abstract/Free Full Text]

9 Bakris GL, Burnett JC Jr. A role for calcium in radiocontrast-induced reductions in renal hemodynamics. Kidney Int (1985) 27:465–8.[Web of Science][Medline]

10 Barrett BJ, Parfrey PS. Clinical practice. Preventing nephropathy induced by contrast medium. N Engl J Med (2006) 354:379–86.[Free Full Text]

11 Beeri R, Symon Z, Brezis M, et al. Rapid DNA fragmentation from hypoxia along the thick ascending limb of rat kidneys. Kidney Int (1995) 47:1806–10.[Web of Science][Medline]

12 Benigni A, Perico N, Remuzzi G. Endothelin antagonists and renal protection. J Cardiovasc Pharmacol (2000) 35:S75–8.[Web of Science][Medline]

13 Berns AS. Nephrotoxicity of contrast media. Kidney Int (1989) 36:730–40.[Web of Science][Medline]

14 Bourin M, Jolliet P, Ballereau F. An overview of the clinical pharmacokinetics of x-ray contrast media. Clin Pharmacokinet (1997) 32:180–93.[Web of Science][Medline]

15 Brezis M, Epstein FH. A closer look at radiocontrast-induced nephropathy. N Engl J Med (1989) 320:179–81.[Web of Science][Medline]

16 Brown R, Ollerstam A, Johansson B, et al. Abolished tubuloglomerular feedback and increased plasma renin in adenosine A1 receptor-deficient mice. Am J Physiol Regul Integr Comp Physiol (2001) 281:R1362–7.[Abstract/Free Full Text]

17 Chalmers N, Jackson RW. Comparison of iodixanol and iohexol in renal impairment. Br J Radiol (1999) 72:701–3.[Abstract]

18 Christiansen C. X-ray contrast media—an overview. Toxicology (2005) 209:185–7.[CrossRef][Web of Science][Medline]

19 Cohan RH, Dunnick NR. Intravascular contrast media: adverse reactions. Am J Roentgenol (1987) 149:665–70.[Free Full Text]

20 Conzen PF, Kharasch ED, Czerner SF, et al. Low-flow sevoflurane compared with low-flow isoflurane anesthesia in patients with stable renal insufficiency [see comment]. Anesthesiology (2002) 97:578–84.[CrossRef][Web of Science][Medline]

21 Davidson C, Stacul F, McCullough PA, et al. Contrast medium use. The Am J Cardiol (2006) 98:42.

22 de Groot AA, van Zwieten PA, Peters SL. Involvement of reactive oxygen species in angiotensin II-induced vasoconstriction. J Cardiovasc Pharmacol (2004) 43:154–9.[CrossRef][Web of Science][Medline]

23 Dobrota M, Powell CJ, Holtz E, Wallin A, Vik H. Biochemical and morphological effects of contrast media on the kidney. Acta Radiol Suppl (1995) 399:196–203.[Medline]

24 Duong MH, MacKenzie TA, Malenka DJ. N-acetylcysteine prophylaxis significantly reduces the risk of radiocontrast-induced nephropathy: comprehensive meta-analysis. Catheter Cardiovasc Interv (2005) 64:471–9.[CrossRef][Web of Science][Medline]

25 Edwards A, Silldforff EP, Pallone TL. The renal medullary microcirculation. Front Biosci (2000) 5:E36–52.[Web of Science][Medline]

26 Eger EI II, Koblin DD, Bowland T, et al. Nephrotoxicity of sevoflurane versus desflurane anesthesia in volunteers. Anesth Analg (1997) 84:160–8.[Abstract]

27 Ergun I, Keven K, Uruc I, et al. The safety of gadolinium in patients with stage 3 and 4 renal failure. Nephrol Dial Transplant (2006) 21:697–700.[Abstract/Free Full Text]

28 Erley C. Concomitant drugs with exposure to contrast media. Kidney Int Suppl (2006) 100:S20–4.[Medline]

29 Fishbane S, Durham JH, Marzo K, Rudnick M. N-acetylcysteine in the prevention of radiocontrast-induced nephropathy. J Am Soc Nephrol (2004) 15:251–60.[Abstract/Free Full Text]

30 Gambaro G, Perazella MA. Adverse renal effects of anti-inflammatory agents: evaluation of selective and nonselective cyclooxygenase inhibitors. J Intern Med (2003) 253:643–52.[CrossRef][Web of Science][Medline]

31 Gare M, Haviv YS, Ben-Yehuda A, et al. The renal effect of low-dose dopamine in high-risk patients undergoing coronary angiography. J Am Coll Cardiol (1999) 34:1682–8.[Abstract/Free Full Text]

32 Goeters C, Reinhardt C, Gronau E, et al. Minimal flow sevoflurane and isoflurane anaesthesia and impact on renal function. Eur J Anaesthesiol (2001) 18:43–50.[Web of Science][Medline]

33 Goldenberg I, Matetzky S. Nephropathy induced by contrast media: pathogenesis, risk factors and preventive strategies. Can Med Assoc J (2005) 172:1461–71.[Abstract/Free Full Text]

34 Gruberg L, Mintz GS, Mehran R, et al. The prognostic implications of further renal function deterioration within 48 h of interventional coronary procedures in patients with pre-existent chronic renal insufficiency. J Am Coll Cardiol (2000) 36:1542.[Abstract/Free Full Text]

35 Gupta RK, Kapoor A, Tewari S, Sinha N, Sharma RK. Captopril for prevention of contrast-induced nephropathy in diabetic patients: a randomised study. Indian Heart J (1999) 51:521–6.[Medline]

36 Haller C, Hizoh I. The cytotoxicity of iodinated radiocontrast agents on renal cells in vitro. Invest Radiol (2004) 39:149–54.[CrossRef][Web of Science][Medline]

37 Haller C, Schick CS, Zorn M, Kubler W. Cytotoxicity of radiocontrast agents on polarized renal epithelial cell monolayers. Cardiovasc Res (1997) 33:655–65.[Abstract/Free Full Text]

38 Hans SS, Hans BA, Dhillon R, Dmuchowski C, Glover J. Effect of dopamine on renal function after arteriography in patients with pre-existing renal insufficiency. Am Surg (1998) 64:432–6.[Web of Science][Medline]

39 Hara T, Fukusaki M, Nakamura T, Sumikawa K. Renal function in patients during and after hypotensive anesthesia with sevoflurane. J Clin Anesth (1998) 10:539–45.[CrossRef][Web of Science][Medline]

40 Heinrich MC, Kuhlmann MK, Grgic A, Heckmann M, Kramann B, Uder M. Cytotoxic effects of ionic high-osmolar, nonionic monomeric, and nonionic iso-osmolar dimeric iodinated contrast media on renal tubular cells in vitro. Radiology (2005) 235:843–9.[Abstract/Free Full Text]

41 Heyman SN, Goldfarb M, Shina A, Karmeli F, Rosen S. N-acetylcysteine ameliorates renal microcirculation: studies in rats. Kidney Int (2003) 63:634–41.[CrossRef][Web of Science][Medline]

42 Hindler K, Shaw AD, Samuels J, Fulton S, Collard CD, Riedel B. Improved postoperative outcomes associated with preoperative statin therapy. Anesthesiology (2006) 105:1260–72.[CrossRef][Web of Science][Medline]

43 Hizoh I, Strater J, Schick CS, Kubler W, Haller C. Radiocontrast-induced DNA fragmentation of renal tubular cells in vitro: role of hypertonicity. Nephrol Dial Transplant (1998) 13:911–8.[Abstract/Free Full Text]

44 Humes HD, Hunt DA, White MD. Direct toxic effect of the radiocontrast agent diatrizoate on renal proximal tubule cells. Am J Physiol (1987) 252:F246–55.[Web of Science][Medline]

45 Ito MK, Talbert RL, Tsimikas S. Statin-associated pleiotropy: possible beneficial effects beyond cholesterol reduction. Pharmacotherapy (2006) 26:85S–97S.[CrossRef][Web of Science][Medline]

46 Itskovitz HD, Stemper J, Pacholczyk D, McGiff JC. Renal prostaglandins: determinants of intrarenal distribution of blood flow in the dog. Clin Sci Mol Med Suppl (1973) 45(Suppl 1):321S–4.[Medline]

47 Jakobsen JA, Lundby B, Kristoffersen DT, Borch KW, Hald JK, Berg KJ. Evaluation of renal function with delayed CT after injection of nonionic monomeric and dimeric contrast media in healthy volunteers. Radiology (1992) 182:419–24.[Abstract/Free Full Text]

48 Just A. Mechanisms of renal blood flow autoregulation: dynamics and contributions. Am J Physiol—Regulatory Integrative & Comparative Physiology (2007) 292:R1–17.

49 Kapoor A, Sinha N, Sharma RK, et al. Use of dopamine in prevention of contrast induced acute renal failure—a randomised study. Int J Cardiol (1996) 53:233–6.[CrossRef][Web of Science][Medline]

50 Karstoft J, Baath L, Jansen I, Edvinsson L. Vasoconstriction of isolated arteries induced by angiographic contrast media. A comparison of ionic and non-ionic contrast media iso-osmolar with plasma. Acta Radiol (1995) 36:312–6.[Web of Science][Medline]

51 Katzberg RW. Urography into the 21st century: new contrast media, renal handling, imaging characteristics, and nephrotoxicity. Radiology (1997) 204:297–312.[Free Full Text]

52 Katzberg RW, Schulman G, Meggs LG, Caldicott WJ, Damiano MM, Hollenberg NK. Mechanism of the renal response to contrast medium in dogs. Decrease in renal function due to hypertonicity. Invest Radiol (1983) 18:74–80.[CrossRef][Web of Science][Medline]

53 Kelly GS. Clinical applications of N-acetylcysteine. Altern Med Rev (1998) 3:114–27.[Medline]

54 Khanal S, Attallah N, Smith DE, et al. Statin therapy reduces contrast-induced nephropathy: an analysis of contemporary percutaneous interventions. Am J Med (2005) 118:843–9.[CrossRef][Web of Science][Medline]

55 Khoury Z, Schlicht JR, Como J, et al. The effect of prophylactic nifedipine on renal function in patients administered contrast media. Pharmacotherapy (1995) 15:59–65.[Web of Science][Medline]

56 Klarenbach SW, Pannu N, Tonelli MA, Manns BJ. Cost-effectiveness of hemofiltration to prevent contrast nephropathy in patients with chronic kidney disease. Crit Care Med (2006) 34:1044–51.[CrossRef][Web of Science][Medline]

57 Kohan DE. Endothelins in the normal and diseased kidney. Am J Kidney Dis (1997) 29:2–26.[Web of Science][Medline]

58 Kshirsagar AV, Poole C, Mottl A, et al. N-acetylcysteine for the prevention of radiocontrast induced nephropathy: a meta-analysis of prospective controlled trials. J Am Soc Nephrol (2004) 15:761–9.[Abstract/Free Full Text]

59 Larsson C, Anggard E. Increased juxtamedullary blood flow on stimulation of intrarenal prostaglandin biosynthesis. Eur J Pharmacol (1974) 25:326–34.[CrossRef][Web of Science][Medline]

60 Lasser EC, Lyon SG. Inhibition of angiotensin-converting enzyme by contrast media. I. In vitro findings. Invest Radiol (1990) 25:698–702.[Web of Science][Medline]

61 Lehnert T, Keller E, Gondolf K, Schaffner T, Pavenstadt H, Schollmeyer P. Effect of haemodialysis after contrast medium administration in patients with renal insufficiency [see comment]. Nephrol Dial Transplant (1998) 13:358–62.[Web of Science][Medline]

62 Liu R, Nair D, Ix J, Moore DH, Bent S. N-acetylcysteine for the prevention of contrast-induced nephropathy. A systematic review and meta-analysis. J Gen Intern Med (2005) 20:193–200.[CrossRef][Web of Science][Medline]

63 Louis BM, Hoch BS, Hernandez C, et al. Protection from the nephrotoxicity of contrast dye. Ren Fail (1996) 18:639–46.[Web of Science][Medline]

64 Marenzi G, Marana I, Lauri G, et al. The prevention of radiocontrast-agent-induced nephropathy by hemofiltration. N Engl J Med (2003) 349:1333–40.[Abstract/Free Full Text]

65 Massy ZA, Nguyen-Khoa T. Oxidative stress and chronic renal failure: markers and management. J Nephrol (2002) 15:336–41.[Web of Science][Medline]

66 Mattson DL, Lu S, Roman RJ, Cowley AW Jr. Relationship between renal perfusion pressure and blood flow in different regions of the kidney. Am J Physiol (1993) 264:R578–83.[Web of Science][Medline]

67 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) 103:368–75.[CrossRef][Web of Science][Medline]

68 Mehran R, Aymong ED, Nikolsky E, et al. A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: development and initial validation. J Am Coll Cardiol (2004) 44:1393–9.[Abstract/Free Full Text]

69 Merten GJ, Burgess WP, Gray LV, et al. Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial [see comment]. JAMA (2004) 291:2328–34.[Abstract/Free Full Text]

70 Moore NN, Lapsley M, Norden AG, et al. Does N-acetylcysteine prevent contrast-induced nephropathy during endovascular AAA repair? A randomized controlled pilot study. J Endovasc Ther (2006) 13:660–6.[CrossRef][Web of Science][Medline]

71 Morcos SK. Contrast media-induced nephrotoxicity—questions and answers. Br J Radiol (1998) 71:357–65.[Abstract]

72 Morcos SK, Thomsen HS, Exley CM. Members of Contrast Media Safety Committee of European Society of Urogenital R. Contrast media: interactions with other drugs clinical tests. Eur Radiol (2005) 15:1463–8.[CrossRef][Web of Science][Medline]

73 Morris TW, Fischer HW. The pharmacology of intravascular radiocontrast media. Annu Rev Pharmacol Toxicol (1986) 26:143–60.[CrossRef][Web of Science][Medline]

74 Mueller C, Buerkle G, Buettner HJ, et al. Prevention of contrast media-associated nephropathy: randomized comparison of 2 hydration regimens in 1620 patients undergoing coronary angioplasty. Arch Intern Med (2002) 162:329–36.[Abstract/Free Full Text]

75 Nakanishi K, Mattson DL, Gross V, Roman RJ, Cowley AW Jr. Control of renal medullary blood flow by vasopressin V1 and V2 receptors. Am J Physiol (1995) 269:R193–200.[Web of Science][Medline]

76 Nallamothu BK, Shojania KG, Saint S, et al. Is acetylcysteine effective in preventing contrast-related nephropathy? A meta-analysis. Am J Med (2004) 117:938–47.[CrossRef][Web of Science][Medline]

77 Nash K, Hafeez A, Hou S. Hospital-acquired renal insufficiency. Am J Kidney Dis (2002) 39:930–6.[CrossRef][Web of Science][Medline]

78 Neumayer HH, Junge W, Kufner A, Wenning A. Prevention of radiocontrast-media-induced nephrotoxicity by the calcium channel blocker nitrendipine: a prospective randomised clinical trial. Nephrol Dial Transplant (1989) 4:1030–6.[Abstract/Free Full Text]

79 Nichols AJ, Ruffolo RR Jr, Brooks DP. The pharmacology of fenoldopam. Am J Hypertens (1990) 3:116S–9S.[Medline]

80 Nikolsky E, Mehran R, Lasic Z, et al. Low hematocrit predicts contrast-induced nephropathy after percutaneous coronary interventions. Kidney Int (2005) 67:706–13.[CrossRef][Web of Science][Medline]

81 Nygren A. Contrast media and regional renal blood flow. A study of the effects of ionic and non-ionic monomeric and dimeric contrast media in the rat. Acta Radiol Suppl (1992) 378:123–35.[Medline]

82 Osswald H, Hermes HH, Nabakowski G. Role of adenosine in signal transmission of tubuloglomerular feedback. Kidney Int Suppl (1982) 12:S136–42.[Medline]

83 Pallone TL, Silldorff EP. Pericyte regulation of renal medullary blood flow. Exp Nephrol (2001) 9:165–70.[CrossRef][Web of Science][Medline]

84 Pallone TL, Zhang Z, Rhinehart K. Physiology of the renal medullary microcirculation. Am J Physiol Renal Physiol (2003) 284:F253–66.[Abstract/Free Full Text]

85 Pannu N, Manns B, Lee H, Tonelli M. Systematic review of the impact of N-acetylcysteine on contrast nephropathy. Kidney Int (2004) 65:1366–74.[CrossRef][Web of Science][Medline]

86 Persson PB. Tubuloglomerular feedback in adenosine A1 receptor-deficient mice. Am J Physiol Regul Integr Comp Physiol (2001) 281:R1361.[Free Full Text]

87 Persson PB, Tepel M. Contrast medium-induced nephropathy: the pathophysiology. Kidney Int Suppl (2006) 100:S8–10.[Medline]

88 Persson PB, Hansell P, Liss P. Pathophysiology of contrast medium-induced nephropathy. Kidney Int (2005) 68:14–22.[CrossRef][Web of Science][Medline]

89 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) 75:1275–83.[Abstract]

90 Rapoport SI, Levitan H. Neurotoxicity of X-ray contrast media. Relation to lipid solubility and blood–brain barrier permeability. Am J Roentgenol Radium Ther Nucl Med (1974) 122:186–93.[Medline]

91 Rauch D, Drescher P, Pereira FJ, Knes JM, Will JA, Madsen PO. Comparison of iodinated contrast media-induced renal vasoconstriction in human, rabbit, dog, and pig arteries. Invest Radiol (1997) 32:315–9.[CrossRef][Web of Science][Medline]

92 Ribeiro L, de Assuncao 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) 65:589–96.[CrossRef][Web of Science][Medline]

93 Rickli H, Benou K, Ammann P, et al. Time course of serial cystatin C levels in comparison with serum creatinine after application of radiocontrast media. Clin Nephrol (2004) 61:98–102.[Web of Science][Medline]

94 Rihal CS, Textor SC, Grill DE, et al. Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention. Circulation (2002) 105:2259–64.[Abstract/Free Full Text]

95 Ruppert V, Leurs LJ, Steckmeier B, Buth J, Umscheid T. Influence of anesthesia type on outcome after endovascular aortic aneurysm repair: an analysis based on EUROSTAR data. J Vasc Surg (2006) 44:16–21. discussion.[CrossRef][Web of Science][Medline]

96 Russo D, Testa A, Della Volpe L, Sansone G. Randomised prospective study on renal effects of two different contrast media in humans: protective role of a calcium channel blocker. Nephron (1990) 55:254–7.[Web of Science][Medline]

97 Schnackenberg CG. Physiological and pathophysiological roles of oxygen radicals in the renal microvasculature. Am J Physiol- Regulatory Integrative & Comparative Physiology (2002) 282:R335–42.

98 Scott JA, King GL. Oxidative stress and antioxidant treatment in diabetes. Ann NY Acad Sci (2004) 1031:204–13.[CrossRef][Web of Science][Medline]

99 Sedeek MH, Llinas MT, Drummond H, et al. Role of reactive oxygen species in endothelin-induced hypertension. Hypertension (2003) 42:806–10.[Abstract/Free Full Text]

100 Shammas NW, Kapalis MJ, Harris M, McKinney D, Coyne EP. Aminophylline does not protect against radiocontrast nephropathy in patients undergoing percutaneous angiographic procedures [see comment]. J Invasive Cardiol (2001) 13:738–40.[Medline]

101 Silldorff EP, Kreisberg MS, Pallone TL. Adenosine modulates vasomotor tone in outer medullary descending vasa recta of the rat. J Clin Invest (1996) 98:18–23.[Web of Science][Medline]

102 Solomon R, Werner C, Mann D, D’Elia J, Silva P. Effects of saline, mannitol, and furosemide to prevent acute decreases in renal function induced by radiocontrast agents. N Engl J Med (1994) 331:1416–20.[Abstract/Free Full Text]

103 Spangberg-Viklund B, Berglund J, Nikonoff T, Nyberg P, Skau T, Larsson R. Does prophylactic treatment with felodipine, a calcium antagonist, prevent low-osmolar contrast-induced renal dysfunction in hydrated diabetic and nondiabetic patients with normal or moderately reduced renal function? Scand J Urol Nephrol (1996) 30:63–8.[Web of Science][Medline]

104 Spargias K, Alexopoulos E, Kyrzopoulos S, et al. Ascorbic acid prevents contrast-mediated nephropathy in patients with renal dysfunction undergoing coronary angiography or intervention. Circulation (2004) 110:2837–42.[Abstract/Free Full Text]

105 Stacul F, Adam A, Becker CR, et al. Strategies to reduce the risk of contrast-induced nephropathy. Am J Cardiol (2006) 98:59.[CrossRef]

106 Sterner G, Frennby B, Kurkus J, Nyman U. Does post-angiographic hemodialysis reduce the risk of contrast-medium nephropathy? Scand J Urol Nephrol (2000) 34:323–6.[CrossRef][Web of Science][Medline]

107 Stevens MA, McCullough PA, Tobin KJ, et al. A prospective randomized trial of prevention measures in patients at high risk for contrast nephropathy: results of the P.R.I.N.C.E. Study. Prevention of Radiocontrast Induced Nephropathy Clinical Evaluation. J Am Coll Cardiol (1999) 33:403–11.[Abstract/Free Full Text]

108 Stone GW, McCullough PA, Tumlin JA, et al. Fenoldopam mesylate for the prevention of contrast-induced nephropathy: a randomized controlled trial. JAMA (2003) 290:2284–91.[Abstract/Free Full Text]

109 Story DA, Poustie S, Liu G, McNicol PL. Changes in plasma creatinine concentration after cardiac anesthesia with isoflurane, propofol, or sevoflurane: a randomized clinical trial. Anesthesiology (2001) 95:842–8.[CrossRef][Web of Science][Medline]

110 Suleiman MY, Passannante AN, Onder RL, Greene-Helms WF, Perretta SG. Alteration of renal blood flow during epidural anesthesia in normal subjects. Anesth Analg (1997) 84:1076–80.[Abstract]

111 Sun D, Samuelson LC, Yang T, et al. Mediation of tubuloglomerular feedback by adenosine: evidence from mice lacking adenosine 1 receptors. Proc Natl Acad Sci USA (2001) 98:9983–8.[Abstract/Free Full Text]

112 Taylor AJ, Hotchkiss D, Morse RW, McCabe J. PREPARED: Preparation for Angiography in Renal Dysfunction: a randomized trial of inpatient vs outpatient hydration protocols for cardiac catheterization in mild-to-moderate renal dysfunction. Chest (1998) 114:1570–4.[CrossRef][Web of Science][Medline]

113 Thomsen HS. Nephrotoxicity. In: Trends in Contrast Media—Thomsen HS, Muller RN, Mattrey RF, eds. (1999) New York: Springer. 104.

114 Thomsen HS. Gadolinium-based contrast media may be nephrotoxic even at approved doses. Eur Radiol (2004) 14:1654–6.[Web of Science][Medline]

115 Toprak O, Cirit M, Bayata S, Yesil M, Aslan SL. The effect of pre-procedural captopril on contrast-induced nephropathy in patients who underwent coronary angiography. Anadolu Kardiyol Derg (2003) 3:98–103.[Medline]

116 Trivedi HS, Moore H, Nasr S, et al. A randomized prospective trial to assess the role of saline hydration on the development of contrast nephrotoxicity. Nephron Clin Pract (2003) 93:C29–34.[CrossRef][Web of Science][Medline]

117 Tumlin J, Stacul F, Adam A, et al. Pathophysiology of contrast-induced nephropathy. Am J Cardiol (2006) 98:14K–20K.[Web of Science][Medline]

118 Ueda J, Nygren A, Hansell P, Erikson U. Influence of contrast media on single nephron glomerular filtration rate in rat kidney. A comparison between diatrizoate, iohexol, ioxaglate, and iotrolan. Acta Radiol (1992) 33:596–9.[Web of Science][Medline]

119 Ueda J, Nygren A, Hansell P, Ulfendahl HR. Effect of intravenous contrast media on proximal and distal tubular hydrostatic pressure in the rat kidney. Acta Radiol (1993) 34:83–7.[Web of Science][Medline]

120 Vlietstra RE, Nunn CM, Narvarte J, Browne KF. Contrast nephropathy after coronary angioplasty in chronic renal insufficiency. Am Heart J (1996) 132:1049–50.[CrossRef][Web of Science][Medline]

121 Vogt B, Ferrari P, Schonholzer C, et al. Prophylactic hemodialysis after radiocontrast media in patients with renal insufficiency is potentially harmful. Am J Med (2001) 111:692–8.[CrossRef][Web of Science][Medline]

122 Waybill MM, Waybill PN. Contrast media-induced nephrotoxicity: identification of patients at risk and algorithms for prevention. J Vasc Interv Radiol (2001) 12:3–9.[Web of Science][Medline]

123 Weinstein JM, Heyman S, Brezis M. Potential deleterious effect of furosemide in radiocontrast nephropathy. Nephron (1992) 62:413–5.[Web of Science][Medline]

124 Weisberg LS, Kurnik PB, Kurnik BR. Dopamine and renal blood flow in radiocontrast-induced nephropathy in humans. Ren Fail (1993) 15:61–8.[Web of Science][Medline]

125 Whelton A. Nephrotoxicity of nonsteroidal anti-inflammatory drugs: physiologic foundations and clinical implications. Am J Med (1999) 106:13S–24S.[CrossRef][Medline]

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