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Review Article

Radiographic Contrast Agents, Drugs Useful for Diagnostics, but with Contrast- Induced Nephropathy as Side Effect

Michele Andreucci1*, Teresa Faga1, Francesco Perticone2, Ashour Michael1

1Nephrology Unit, Department of “Health Sciences”, Campus “Salvatore Venuta”, “Magna Graecia” University, Viale Europa, loc. Germaneto, I-88100 Catanzaro, Italy
2Department of “D.S.M.C.”, Campus “Salvatore Venuta”, “Magna Graecia” University, Viale Europa, loc. Germaneto, I-88100 Catanzaro, Italy

*Corresponding AuthorDr. Michele Andreucci, MD, PhD; Associate Professor of Nephrology, “Magna Graecia” University, I-88100 Catanzaro, Italy, E-mail: andreucci@unicz.it

Submitted: 10-20-2014 Accepted: 11-16-2014 Published: 04-06-2015

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Iodinated radiographic contrast agents are drugs very useful in clinical practice to improve the visibility of internal organsand structures in X-ray based imaging techniques. Their use keeps increasing, particularly in less healthy and older patients, with one or more comorbid conditions, such as advanced vascular disease, severe long-standing hypertension, diabetes and impairment of renal function. However, they may have side effects the most frequent being Contrast-Induced Nephropathy (CIN). After a short description of the epidemiology and pathogenesis of CIN, the conditions favoring the development of CIN in patients are discussed, the main ones being pre-existing renal impairment, particularly if secondary to diabetic nephropathy,salt depletion and dehydration, congestive heart failure, age greater than 70 years and concurrent use of nephrotoxic drugs. Then the measures to prevent CIN are suggested, beginning with monitoring renal function, discontinuation of potentially nephrotoxic drugs, use of either iodixanol or iopamidol at the lowest dosage possible. The main procedure for prevention of CIN is an adequate hydration of the patient with either oral water intake or isotonic sodium chloride or sodium bicarbonate infusion. (A long list of references is provided that will enable readers a deep evaluation of the topic).

Keywords: Contrast-Induced Nephropathy; Contrast-Induced Acute Kidney Injury; Acute Renal Failure; Radiographic contrast media;Iodinated contrast material; Renal cell injury


IRCA: Iodinated Radiographic Contrast Agents;
CIN: Contrast-Induced Nephropathy;
CI-AKI: Contrast-Induced Acute Kidney Injury;
CT: Computed Tomography;
MDRD: Modification of Diet in Renal Disease;
eGFR: Estimated Glomerular Filtration Rate;
CKD-EPI: Chronic Kidney Disease Epidemiology Collaboration;
LOCM: Low-Osmolar Contrast Media;
NO: Nitric Oxide;
ROS: Reactive Oxygen Species;
HOCM: High-Osmolar Contrast Media;
IOCM: Iso-Osmolar Contrast Media:
ARF: Acute Renal Failure;
SCr: Serum Creatinine;
RBF: Renal Blood Flow;
CRF: Chronic Renal Failure;
ACEi: Angiotensin-Converting Enzyme inhibitors;
ARBs: Angiotensin II Receptor Blockers;
NCX: Na+/Ca2+ exchanger pumps;
NaC: N-acetylcysteine;
KDIGO: Kidney Disease Improving Global Outcomes;
ERBP: European Renal Best Practice

Iodinated radiographic contrast agents (IRCA) are drugs very useful to improve the visibility of internal organs and structures (Iodine is an important component of contrast media possessesing high-contrast density) in X-ray based imaging, techniques such as radiography, angiography and contrast-enhanced computed tomography (CT) scans, and to perform cardiac catheterizations and percutaneous coronary interventions. IRCA have been in use for over 60 years and their use for imaging and intravascular intervention keeps increasing, particularly in less healthy and older patients, with one or more comorbid conditions [1].

IRCA may have side effects, sometimes just mild inconvenience such as itching, in rare cases a life-threatening emergency [2]. Among the side effects associated with the use of intravenous or intra-arterial injection of IRCA, contrast-induced nephropathy
(CIN) is undoubtedly the most important and frequent well known adverse reaction [3].

Contrast-Induced Nephropathy (CIN)

We define CIN as an Acute Renal Failure (ARF) occurring 24-72 hours after the exposure to intravascular injection of IRCA that cannot be attributed to other causes.

It is usually a non-oliguric ARF with asymptomatic transient decline in renal function, peaking on the third to fifth day, and returning to baseline within 10–14 days [4]. It is mirrored by an absolute (0.5 mg/dL or greater) or relative (by 25% or greater) increase in serum creatinine (SCr) from baseline or, better, by a decrease (to 30-60 mL/min - renal insufficiency – or less) in the estimated glomerular filtration rate (eGFR), i.e. the creatinine clearance calculated using either the MDRD (Modification of Diet in Renal Disease) calculation [5] or the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation [6], or alternatively by the very simple Cockcroft- Gault formula [7].

CIN may also be referred to as Contrast-Induced Acute Kidney Injury (CI-AKI). In some cases, CIN may cause a more severe impairment of renal function with oliguria (<400 mL/24 hrs), requiring dialysis. In these cases the mortality is high.

The clinical feature and the management of CIN are the same as that for ARF due to other causes [8-10].

CIN occurs in up to 5% of hospitalized patients who exhibit normal renal function prior to the injection of contrast medium [11] and in about 2% [1] or even 1% of outpatients with eGFR >45 ml/min per 1.73 m2 [12].

Thus, CIN is uncommon in patients with normal pre-existing renal function [13]. It occurs more frequently in patients with renal impairment, particularly those with diabetic nephropathy [14]. Among all procedures utilizing contrast agents for either diagnostic or therapeutic purposes, coronary angiography and percutaneous coronary interventions are associated with the highest rates of CIN [15]. This is mainly related (A) to intra-arterial injection: IRCA seem to be more nephrotoxic when given intra-arterially because of the higher acute intrarenal concentration [16,17], particularly if the arterial injection is suprarenal [18-24]; (B) to the high dosage of the contrast used and (C) to the type of patients who are usually in advanced age, with one or more comorbid conditions, such as advanced vascular disease, severe long-standing hypertension, diabetes and some renal function impairment [25,26].

In a retrospective study on 11,588 patients undergoing CT either without contrast or with the low-osmolar contrast medium iohexol or the iso-osmolar contrast medium iodixanol, Bruce et al [27] observed that the incidence of CIN in the low-osmolar contrast medium group was similar to that of the control group up to an SCr level of 1.8 mg/dL; but an SCr above 1.8 mg/dL was associated with a higher incidence of CIN in the low-osmolar contrast medium group.

In another retrospective study performed in 20,242 adult inpatients undergoing computed tomography (CT) (10,121 untreated and 10,121 receiving i.v. IRCA), Davenport et al [28] found that i.v. low-osmolality IRCA injection is a risk factor for nephrotoxicity in patients with a stable eGFR <30 mL/ min/1.73 m2; no nephrotoxicity was observed in patients with a pre-CT eGFR >45 mL/min/1.73 m2. The Authors concluded that i.v. IRCA is a nephrotoxic risk factor, but not in patients with a stable SCr <1.5 mg/dL or eGFR >45 mL/min/1.73 m2 [28].

We must admit, however, that some Authors do not believe that IRCA are responsible for impairment of renal function. Thus, McDonald et al [29] carried out a retrospective study to determine the causal association and effect of IRCA exposure on the incidence of CIN. All abdominal, pelvic, and thoracic CT scans from 2000 to 2010 were identified at a single facility, including subjects treated with IRCA (contrast group) and those who had not undergone IRCA injection (non-contrast group). Scan recipients were divided into three subgroups: low- (SCr 1.5 mg/dL), medium- (SCr 1.5–2.0 mg/dL), and high-risk (SCr 2.0 mg/dL) for CIN by using baseline SCr level. The incidence of CIN (SCr >0.5 mg/dL above baseline) was compared between contrast and non-contrast groups after proper corrections. A total of 157,140 scans among 53,439 unique patients associated with 1,510,001 SCr values were identified. CIN risk was not significantly different between contrast and non-contrast groups in any risk subgroup after propensity score adjustment by using reported risk factors of CIN. The Authors concluded that, following adjustment for presumed risk factors, the incidence of CIN was not significantly different from contrast material– independent ARF, suggesting that intravenous iodinated contrast media may not be the causative agent in diminished renal function after contrast material administration. But the same Authors add that their data cannot directly refute the existence of intravenous CIN and that they indicate that accepted SCr-based definitions of CIN cannot identify this phenomenon as a distinct clinical entity.

Pathogenesis of CIN

The mechanisms of nephrotoxicity by IRCA are quite complex and not fully understood [30]. Many factors are involved, including an initial increase followed by a more prolonged decrease in renal blood flow (RBF), a decrease in nitric oxide (NO), medullary vasoconstriction and severe reduction in medullary blood flow with renal ischaemia, severe medullary hypoxia, intracellular Ca2+ overload, direct tubular damage, formation of reactive oxygen species (ROS) [31-36], increased intratubular pressure secondary to contrast-induced diuresis, increase of tubular fluid viscosity, tubular obstruction and finally a decrease in GFR [37].

In vivo experiments in rats have demonstrated that the decrease in cortical and medullary blood flow induced by IRCA is partly accounted for by the downregulation of endogenous renal cortical and medullary NO synthesis [38]. The use of the superoxide dismutase (SOD) mimetic Tempol reduced iodixanol- induced vasoconstriction [39]. A recombinant manganese SOD administered in vivo to rats undergoing diatrizoate treatment caused an improvement in GFR and a reduction in renal histologic damage [40].

IRCA have also a direct toxicity on tubular epithelium and on endothelial cells. In vitro cell culture studies have shown that all IRCA cause a decrease in cell viability [41-45] and changes in morphology [46,47]. Endothelial damage by iodixanol was also noted by Sendeski et al [48] using isolated human and rat descending vasa recta. The biochemical changes underlying these effects have been extended to studying changes in major intracellular signalling pathways involved in cell survival, death and inflammation [43-45,49-52] in cultured primary human renal tubular cells [53,54]. IRCA cause alteration of mitochondrial enzyme activity and apoptosis of renal tubular cells [54-60].

Recent work has shown that contrast media affect the membrane skeleton of erythrocytes, with iopromide causing drastic changes in the band3-spectrin network that may contribute to microcirculatory disorders and gas transport, contributing to tissue hypo-oxygenation [61].

The iodinated radiographic contrast agents (IRCA)

IRCA have different osmolalities and different viscosities (Table). The ionic High-Osmolar Contrast Media (HOCM, e.g. diatrizoate) have an osmolality between 1500 and 1800 mOsm/ kg, 5 to 8 times the osmolality of plasma. Nonionic Low-Osmolar Contrast Media (LOCM e.g. iohexol) have an osmolality between 600 and 850 mOsm/kg, 2–3 times the osmolality of plasma. Nonionic Iso-Osmolar Contrast Media (IOCM e.g. iodixanol) have an osmolality of 290-300 mOsm/kg, the same osmolality as plasma [37,62].

HOCM have a greater cytotoxic effects on proximal tubular cells in vitro than do LOCM or IOCM. At equal iodine concentrations (300 mg I/mL), the HOCM ioxithalamate showed stronger cytotoxic effects than did other IRCA [42]. The use of LOCM rather than HOCM is beneficial in reducing the incidence of CIN in patients with pre-existing renal failure [63-66]. Thus, the HOCM are used less frequently. There is no difference in the cytotoxicity of LOCM iomeprol and IOCM iodixanol at equal iodine concentrations in renal proximal tubular cells in vitro [67]. Recent studies and meta-analyses have shown no significant difference in the incidence of CIN between IOCM and LOCM [67-70] with the exception of LOCM iohexol that is more nephrotoxic [63,71]. However, in a study of Nguyen et al [72] involving 117 patients (83 men, 34 women; mean age, 64 years; range 18–86 years) with an impaired renal function, even if the differences between the two compared agents (iodixanol and iopromide) was not drastic, fewer patients in the iodixanol group (8.5% versus 27,8%) had an increase in serum creatinine of 0,5 mg/dL (or more) and a reduction in GFR of 5 ml/min (or more) (42,3% versus 24,1%).

IRCA have different viscosities (Table). The low osmolality achieved with the IOCM has been obtained at the price of increased viscosity; at comparable iodine concentrations and x-ray attenuation, the non-ionic dimeric IOCM have about twice the viscosity of non-ionic monomeric LOCM [73-75].

Patient conditions favoring the development of CIN

According to the European Society of Urogenital Radiology patient conditions favoring CIN are represented by pre-existing renal impairment particularly when associated with diabetes mellitus, salt depletion and dehydration, congestive heart failure, an age greater than 70 years and concurrent use of nephrotoxic drugs [76,77].

The worst condition is a pre-existing impairment of renal function, irrespective of cause. The incidence of CIN in patients with chronic renal failure (CRF) ranges from 14.8 to 55% [15]. The lower the eGFR, the greater is the risk of CIN. An eGFR of 60 ml/min/1.73m2 is a reliable cutoff point for identifying patients at high risk for the development of CIN [4]. Diabetes mellitus is the second most important condition, particularly when associated with renal insufficiency [78]. At any given degree of baseline eGFR, diabetes doubles the risk of developing CIN. The incidence of CIN in diabetic patients varies from 5.7 to 29.4% [15,79]. The concomitant use of nephrotoxic drugs such as aminoglycosides, cyclosporin A, amphotericin, cisplatin and nonsteroidal anti-inflammatory drugs is another condition favoring CIN [81,82].

The role of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) in the incidence of CIN is still controversial [78]. Many Authors suggest to discontinue these drugs in patients with CRF [80,83-88]. Others deny such a procedure [89]. KDIGO does not suggest to discontinue these medications prior to contrast administration [90].

Other conditions favouring CIN include prolonged hypotension [16, 91], severe dehydration, reduction of ‘effective’ intravascular volume due to congestive heart failure, liver cirrhosis, or salt depletion secondary to abnormal fluid losses associated with insufficient salt intake [16,34,91-93].

Dehydration and salt depletion deserve a special discussion. Dehydration is the decrease of body water, as it occurs sometimes in old patients due to impaired sensation of thirst [93]. But the term dehydration is frequently used to indicate salt and water depletion. Dehydration and salt depletion are responsible for the reduction of the ‘effective’ circulating blood volume, i.e. the relative fullness of the arterial tree as determined by cardiac output, peripheral vascular resistance and total blood volume [9]. A reduction of the ‘effective’ circulating blood volume may be due to congestive heart failure, compromised left ventricle systolic performance, prolonged hypotension, liver cirrhosis , nephrotic syndrome or salt depletion.

Measures for prevention of CIN

The first general rule is that in any patient undergoing any radiographic procedure, renal function has to be measured before and after the procedure; in patients at high risk of CIN these parameters should be monitored before and once daily for 5 days after the use of IRCA [16,94].

The second measure is that potentially nephrotoxic drugs (aminoglycosides, vancomycin, amphotericin B, metformin and nonsteroidal anti-inflammatory drugs) should be discontinued before the IRCA injection [94]. For aminoglycosides the ERBP [95] suggests to not using more than one shot of aminoglycosides for the treatment of infections in patients with normal kidney function in steady state, and that the drugs should be administered as a single daily dose rather than multiple- dose, with their levels monitored. Metformin, an oral antihyperglycemic drug used to treat type II diabetes, stimulates intestinal production of lactic acid; a severe lactic acidosis that can be fatal may occur in case of renal failure, since the drug is excreted unchanged almost entirely by the kidneys. Thus, metformin should be discontinued at least 12 hours before the IRCA injection and not be resumed for a minimum of 36 hours after the procedure (or longer if the SCr has not returned to baseline) [96].

The third measure is the choice of the least nephrotoxic radiocontrast agent. Iodixanol (IOCM) and iopamidol (LOCM) appear to be contrast agents of choice to reduce risk of CIN [97]. The fourth measure is to use the lowest dosage possible of IRCA. High doses of IRCA are required in coronary angiography and percutaneous coronary intervention. For these procedures, some formulas have been suggested to calculate the least dangerous dosage [94]:

(A) Cigarroa’s formula [98]: 5 mL of contrast per kg b.w./SCr (mg/dL). The maximum dose acceptable is 300 mL for diagnostic coronary arteriography.
(B) Laskey’s formula [99]: volume of contrast to calculated creatinine clearance ratio with a cut-off point of the ratio at 3.7 or,
better, at 2.0: below a ratio of 2.0 CIN would be a rare complication, but would increase dramatically at a ratio of 3.0 [97, 100].
(C) Ratio of grams of iodine to the calculated creatinine clearance; a ratio of 1.42, or even better a ratio of 1.0, would prevent CIN [97].

The fifth measure is to ensure an adequate hydration of the patient [101,102]. The old practice to limit fluid intake starting the day before IRCA administration must be abolished. Instead, we have to give volume supplementation: e.g. 500 mL of water orally before and 2,500 mL for 24 hours after contrast administration in order to secure urine output of at least 1 mL/min in a non-dehydrated patient [103]. In high-risk patients it is suggested an i.v. infusion of 0.9% saline at a rate of approximately 1 mL/kg b.w. per hour, beginning 6–12 hours before the procedure and continuing for up to 12–24 hours after the radiographic examination, if urine output is appropriate and cardiovascular condition allows it [16, 101]. Hydration, in fact, causes expansion of intravascular volume, suppression of renin- angiotensin system and consequent reduction of renal vasoconstriction and hypoperfusion. Furthermore, the increased diuresis will limit the duration of IRCA contact with renal tubular walls and consequently the toxicity on tubular epithelium [104,105].

On the basis of clinical studies and meta-analysis some Authors prefer sodium bicarbonate hydration to sodium chloride [106-114]. This because urinary excretion of bicarbonate decreases the acidification of urine, thereby reducing the production and increasing the neutralization of oxygen free radicals; this will protect the kidney from injury by contrast agents [109,110,115,116]. The dosage suggested for an emergency coronary angiography or intervention is: 154-mEq/L infusion of sodium bicarbonate as a bolus of 3 mL/kg b.w./hour for 1 hour before the administration of contrast agent, followed by 1 mL/kg/hour for 6 hours during and after the procedure [107]. The ERBP “recommends volume expansion with either isotonic sodium chloride or sodium bicarbonate solutions, rather than no volume expansion, in patients at increased risk for CIN” [95].

The sixth measure is the use of drugs protecting the kidneys. We have mentioned that ROS have been proven to play an important role in the renal damage caused by IRCA. Hence, antioxidants represent the main type of drugs that has been shown to reduce the incidence of CIN. The antioxidant N-acetylcysteine [117] is believed to act either as a free-radical scavenger or as a reactive sulfhydryl compound as well as a factor able to increase the vasodilating effect of NO [16,33,118]. Pretreatment with NAC has been demonstrated to reduce IRCA-induced cytotoxicity in human embryonic kidney cells treated with ioxithalamate, iopromide and iodixanol [119] and to ameliorate the ischemic ARF in animal models [120]. Its use in humans has given controversial results [8,121-129]. We may give NaC to high-risk patients either as an oral dose of 600 mg twice daily the day before and the day of procedure [16] or, in patients unable to take the drug orally, with an i.v. dose of 150 mg/kg over half an hour before the procedure or 50 mg/kg administered over 4 hours [37,94,122].

Conflicting results have been obtained with another antioxidant, ascorbic acid [119,130-132] at a dosage of 3 g orally 2 hours before the procedure and 2 g during the night and in the morning after the procedure. In a recent meta-analysis, with 1536 patients who completed the trial, patients receiving ascorbic acid had a 33% reduced risk of developing CIN [133]. Tasanarong et al [134] have used α-tocopherol and γ-tocopherol as antioxidants to prevent CIN: the oral administration of either 350 mg/day of α-tocopherol or 300 mg/day of γ-tocopherol 5 days prior to the coronary procedure and continued for a further 2 days post-procedure, in combination with 0.9% saline (1 mL/kg/h for 12 hours before and 12 hours after) was demonstrated to be effective in protecting against CIN in patients with CRF undergoing coronary procedures with Iopromide: CIN developed in 14.9% of cases in the placebo group, but only in 4.9% and 5.9% in the α- and γ-tocopherol groups, respectively [134].

Nebivolol, a third-generation β1-adrenergic receptor antagonist, has been suggested for protecting the kidney against CIN because of its antioxidant and NO-mediated vasodilating action [135,136]: at a dosage of 5 mg/day for one week or 5 mg every 24 hours for 4 days, it decreased the incidence of CIN in patients with renal dysfunction undergoing coronary angiography [137,138].

Several studies have demonstrated the protective effect of statins against the CIN [139-145] because of their antioxidant, anti-inflammatory, and antithrombotic properties and their vasodilator activity mediated by NO, which improves renal microcirculation [146,147]. Rosuvastatin has been shown to be nephroprotective at a dosage of 10 mg/day for five days, two days before, three days post the radiographic procedure, in diabetic patients with CRF undergoing coronary/peripheral arterial angiography [139], and at a dosage of 40 mg on admission followed by 20 mg/day in patients with acute coronary syndrome [140]. Atorvastatin (40 mg/day 3 days before the procedure or 80 mg 12 hours before intervention with another 40-mg pre-procedure, followed by long-term treatment of 40 mg/day) had a protective effect on renal function preventing CIN and shortening hospital stay [148,149].

The outer renal medulla, under normal physiological conditions, receives little oxygen (O2) because of its distance from the descending vasa recta, despite its high local O2 consumption due to the important active tubular reabsorption in S3 segments of proximal renal tubules and in the medullary thick ascending limb of the Henle’s loops that are here located. IRCA induce also an osmotic diuresis that will increase fluid delivery and consequently tubular reabsorption in the ascending limb of Henle’s loops, thereby increasing both energy need and O2 consumption: the result will be a worsening of renal medullary hypoxia [30,150,151]. Thus, it has been suggested to use furosemide to decrease the reabsorption in the thick ascending limb of Henle’s loops, thereby reducing renal medullary hypoxia, a crucial factor in IRCA nephrotoxicity. But several studies have demonstrated no protection against CIN or even deleterious effects of this diuretic [152-154], leading to the suggestion that diuretics should be even avoided before contrast exposure [83]. However, Marenzi et al [155] have suggested the perfect combination of hydration plus furosemide: this was obtained by delivering i.v. fluid in an amount exactly matched to the volume of urine produced by the patient under the effect of furosemide; this procedure has been called ‘Renal Guard’ by Guastoni et al [156]: the result was a significantly lower incidence of CIN when this procedure was compared to the patients treated with hydration only.

Under physiological conditions, the Na+/Ca2+ exchanger (NCX), pumps Ca2+ out of the renal tubular epithelial cells using the Na+ concentration gradient across the cell membrane to keep the intracellular Ca2+ levels low. In pathological conditions, such as CIN, NCX can reversely extrude Na+ for Ca2+ influx resulting in intracellular Ca2+ overload that is believed to be a key factor in ischemic cell injury in CIN [37,157]. Thus, calcium channel blockers have been hypothesized to have protective effects against CIN. However, their use has given controversial results, protective for some Authors [158,159], non-protective according to others [160-162].

Very recently, Pequero et al [163] have suggested to use Nitrates to reduce the incidence of CIN. In a retrospective, single- center study these Authors investigated whether the use of nitrate in 199 patients undergoing percutaneous coronary artery intervention could reduce the incidence of CIN. Post-procedure renal function was compared between 112 patients who received nitrates prior to coronary intervention and 87 who did not. Multivariate logistic regression analysis demonstrated that nitrate use was independently correlated with a reduction in the development of CIN (OR = 0.334, 95% CI 0.157-0.709, p = 0,004). Additionally, amongst various methods of nitrate administration, intravenous infusion was shown to be the most efficacious route in preventing renal impairment (OR = 0.42, 95% CI 0.20-0.90, p = 0,03). According to these data, the use of nitrates prior to PCI, particularly as intravenous nitroglycerin infusion, may be associated with a decreased incidence of CIN.

Treatment by dialysis

Treatment by haemodialysis or haemofiltration immediately after the radiographic procedure has been suggested with the purpose to remove IRCA. Schindler et al [164] demonstrated, in patients with CRF (the great majority in chronic dialysis), that different dialysis techniques remove IRCA, and that highflux hemodialysis and hemodiafiltration remove IRCA more effectively than low-flux hemodialysis and hemofiltration. But Lehnert et al [165] demonstrated that, even though hemodialysis eliminates IRCA, it does not prevent the occurrence of CIN. Vogt et al [166] performed a randomized trial to test whether CIN can be avoided by prophylactic hemodialysis immediately after the administration of low-osmolality IRCA in patients with CRF (baseline serum creatinine level >2.3 mg/dL); renal function was recorded before and during the 6 days after administration of contrast media. Hemodialysis did not diminish the rate of CIN. These studies suggest that, even when dialysis is performed immediately, the early damage has already occurred and cannot be reversed [167]. Hence, the effects of hemodialysis have been negative [168].

There are, however, a few exceptions. Lee et al [169] have compared intravenous isotonic saline and prophylactic hemodialysis in 82 patients with CRF referred for coronary angiography; they randomly received either normal saline intravenously and prophylactic hemodialysis (dialysis group, n = 42) or fluid supplement only (control group, n = 40). Prophylactic hemodialysis lessened the reduction in creatinine clearance within 72 hours (<0,001). Temporary renal replacement therapy was required in 35% of the control patients and in 2% of the dialysis group; five of the controls and none of the dialysis patients required long-term dialysis after discharge (p=0,018). For the patients not requiring chronic dialysis, 13 in the control group (37%) and 2 in the dialysis group (5%) had an increase in SCr at discharge of more than 1 mg/dL from baseline (p < 0,001). The Authors concluded that the prophylactic hemodialysis is effective in improving renal outcome in CRF patients undergoing coronary angiography.

Marenzi et al [170] have demonstrated that hemofiltration is an effective strategy for preventing CIN in patients with CRF undergoing cardiovascular procedures provided that is performed for 6 hours before and for 18 to 24 hours after contrast exposure.

Better results have been obtained with continuous venovenous hemofiltration (CVVH). Thus, La Manna et al [171] have proposed the CVVH technique in preventing CIN in high-risk patients undergoing interventional cardiovascular procedures involving the administration of IRCA. CVVH in 12 patients with severe chronic renal impairment and at least two severe co-morbidities significantly improved eGFR and SCr after the use of iodixanol. Renal function, in fact, evaluated as SCr and as e-GFR, did not worsen but was improved when the patients left hospital 7 days after the radiological procedure, being significantly better than that on hospital admission. More recently, Guastoni et al [172] performed CVVH in 53 consecutive patients with eGFR <30 ml/min/1.73 m2 undergoing diagnostic or interventional coronary procedures using iopamidol; CVVH was started immediately after the angiographic procedure. Sixhour CVVH resulted in iopamidol removal comparable with that of 12-hour diuresis (i.e. 43% vs 42%). CIN occurred in only 7.5% of patients of the total population investigated.

Table-Iodinated Contrast Media Commonly Used in Clinical Practice

nephro table 13.1
The osmolality of contrast media is compared with the osmolality of plasma. HOCM = High Osmotic Contrast Media have the highest osmolality, i.e. 5–8 times the osmolality of plasma.

LOCM = Low Osmotic Contrast Media have an osmolality still higher than plasma, i.e. 2–3 times the osmolality of plasma.
IOCM = Iso Osmotic Contrast Media have the same osmolality as plasma. Cps: Viscosity in Centipoise.
(Reproduced from [4] with permission.)
Data of viscosity from [173].

Conflicts of Interest

All Authors have no potential conflicts of interest to disclose.


Dr. Ashour Michael is recipient of an “Assegno di Ricerca” (“Research Check”) for 2014 and 2015 given by the “Magna Graecia” University of Catanzaro (Italy).

M.A. has been recipient of a grant from the Italian Society of Nephrology (“S.I.N.”) for the years 2012 and 2014 and for a financial research support from Amgen.




1.Solomon R. Contrast-induced acute kidney injury: is there a risk after intravenous contrast? Clin J Am Soc Nephrol. 2008, 3(5): 1242-1243.

2.Lightfoot CB, Abraham RJ, Mammen T, Abdolell M, Kapur S et al. Survey of radiologists' knowledge regarding the management of severe contrast material-induced allergic reactions. Radiology. 2009, 251(3): 691-696.

3.Andreucci M. [Radiographic contrast nephropathy]. G Ital Nefrol. 2014, 31(5).

4.Andreucci M, Solomon R, Tasanarong A. Side Effects of Radiographic Contrast Media: Pathogenesis, Risk Factors, and Prevention. Biomed Res Int. 2014, 2014: 741018.

5.Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999, 130(6): 461-470.

6.Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009, 150(9): 604-612.

7.Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976, 16(1): 31-41.

8.Briguori C, Colombo A, Violante A, Balestrieri P, Manganelli F et al. Standard vs double dose of N-acetylcysteine to prevent contrast agent associated nephrotoxicity. Eur Heart J. 2004, 25(3): 206-211.

9.Andreucci VE, Fuiano G, Russo D, Andreucci M. Vasomotor nephropathy in the elderly. Nephrol Dial Transplant 13 Suppl. 1998, 7: 17-24.

10.Andreucci VE, Fuiano G, Stanziale P, Andreucci M. Role of renal biopsy in the diagnosis and prognosis of acute renal failure. Kidney Int Suppl. 1998, 66: S91-S95.

11.Curtis LM, Agarwal A. HOpe for contrast-induced acute kidney injury. Kidney Int. 2007, 72(8): 907-909.

12.Weisbord SD, Palevsky PM. Prevention of contrast-induced nephropathy with volume expansion. Clin J Am Soc Nephrol. 2008, 3(1): 273-280.

13.Andreucci M. Side effects of radiographic contrast media. Biomed Res Int. 2014, 2014: 872574.

14.Katzberg RW, Newhouse JH. Intravenous contrast medium- induced nephrotoxicity: is the medical risk really as great as we have come to believe? Radiology. 2010, 256(1): 21-28.

15.Mehran R, Nikolsky E. Contrast-induced nephropathy: definition, epidemiology, and patients at risk. Kidney Int Suppl. 2006, (1100): S11-S15.

16.Gleeson TG, Bulugahapitiya S. Contrast-induced nephropathy. AJR Am J Roentgenol. 2004, 183(6): 1673-1689.

17.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(3): 290-301.

18.Byrd L, Sherman RL. Radiocontrast-induced acute renal failure: a clinical and pathophysiologic review. Medicine (Baltimore). 1979, 58(3): 270-279.

19.Harkonen S, Kjellstrand C. Contrast nephropathy. Am J Nephrol. 1981, 1: 69-77.

20.Khoury GA, Hopper JC, Varghese Z, Farrington K, Dick R et al. Nephrotoxicity of ionic and non-ionic contrast material in digital vascular imaging and selective renal arteriography. Br J Radiol. 1983, 56(669): 631-635.

21.Moore RD, Steinberg EP, Powe NR, Brinker JA, Fishman EK et al. Nephrotoxicity of high-osmolality versus low-osmolality contrast media: randomized clinical trial. Radiology. 1992, 182(3): 649-655.

22.Katzberg RW, Barrett BJ. Risk of iodinated contrast material-- induced nephropathy with intravenous administration. Radiology. 2007, 243(3): 622-628.

23.Campbell DR, Flemming BK, Mason WF, Jackson SA, Hirsch DJ et al. A comparative study of the nephrotoxicity of iohexol, iopamidol and ioxaglate in peripheral angiography. Can Assoc Radiol J. 1990, 41(3): 133-137.

24.Gomes AS, Baker JD, Martin-Paredero V, Dixon SM, Takiff H et al. Acute renal dysfunction after major arteriography. AJR Am J Roentgenol. 1985, 145(6): 1249-1253.

25.Deray G, Martinez F, Cacoub P, Baumelou B, Baumelou A et al. A role for adenosine calcium and ischemia in radiocontrast- induced intrarenal vasoconstriction. Am J Nephrol. 1990, 10(4): 316-322.

26.Fuiano G, Mancuso D, Indolfi C, Mongiardo A, Sabbatini M et al. Early detection of progressive renal dysfunction in patients with coronary artery disease. Kidney Int. 2005, 68(6): 2773- 2780.

27.Bruce RJ, Djamali A, Shinki K, Michel SJ, Fine JP et al. Background fluctuation of kidney function versus contrast-induced nephrotoxicity. AJR Am J Roentgenol. 2009, 192: 711-718.

28.Davenport MS, Khalatbari S, Dillman JR, Cohan RH, Caoili EM et al. Contrast material-induced nephrotoxicity and intravenous low-osmolality iodinated contrast material. Radiology. 2013, 267(1): 94-105.

29.McDonald RJ, McDonald JS, Bida JP, Carter RE, Fleming CJ et al. Intravenous contrast material-induced nephropathy: causal or coincident phenomenon? Radiology. 2013, 267(1): 106-118.

30.Andreucci M, Faga T, Pisani A, Sabbatini M, Michael A. Acute Kidney Injury by Radiographic Contrast Media: Pathogenesis and Prevention. BioMed Research Int. 2014, 2014: 362725.

31.Giaccia AJ, Simon MC, Johnson R. The biology of hypoxia: the role of oxygen sensing in development, normal function, and disease. Genes Dev. 2004, 18(18): 2183-2194.

32.Murphy SW, Barrett BJ, Parfrey PS. Contrast nephropathy. J Am Soc Nephrol. 2000, 11(1): 177-182.

33.Heyman SN, Rosen S, Khamaisi M, Idee JM, Rosenberger C. Reactive oxygen species and the pathogenesis of radiocontrast- induced nephropathy. Invest Radiol. 2010, 45(4): 188- 195.

34.Detrenis S, Meschi M, Musini S, Savazzi G. Lights and shadows on the pathogenesis of contrast-induced nephropathy: state of the art. Nephrol Dial Transplant. 2005, 20(8): 1542- 1550.

35.Pisani A, Riccio E, Andreucci M, Faga T, Ashour M et al. Role of reactive oxygen species in pathogenesis of radiocontrast-induced nephropathy. Biomed Res Int. 2013, 2013: 868321.

36.Sabbatini M, Santillo M, Pisani A, Paterno R, Uccello F et al. Inhibition of Ras/ERK1/2 signaling protects against postischemic renal injury. Am J Physiol Renal Physiol. 2006, 290(6): F1408-F1415.

37.Andreucci M, Faga T, Pisani A, Sabbatini M, Michael A. Pathogenesis of Acute Renal Failure induced by iodinated radiographic contrast media. Austin J Nephrol Hypertens. 2014, 1(1): 1005.

38.Myers SI, Wang L, Liu F, Bartula LL. Iodinated contrast induced renal vasoconstriction is due in part to the downregulation of renal cortical and medullary nitric oxide synthesis. J Vasc Surg. 2006, 44(2): 383-391.

39.Sendeski M, Patzak A, Pallone TL, Cao C, Persson AE et al. Iodixanol, constriction of medullary descending vasa recta, and risk for contrast medium-induced nephropathy. Radiology. 2009, 251(3): 697-704.

40.Pisani A, Sabbatini M, Riccio E, Rossano R, Andreucci M et al. Effect of a recombinant manganese superoxide dismutase on prevention of contrast-induced acute kidney injury. Clin Exp Nephrol. 2014, 18(3): 424-431.

41.Hardiek K, Katholi RE, Ramkumar V, Deitrick C. Proximal tubule cell response to radiographic contrast media. Am J Physiol Renal Physiol. 2001, 280(1): F61-F70.

42.Heinrich MC, Kuhlmann MK, Grgic A, Heckmann M, Kramann B et al. 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(3): 843-849.

43.Andreucci M, Lucisano G, Faga T, Bertucci B, Tamburrini O et al. Differential activation of signaling pathways involved in cell death, survival and inflammation by radiocontrast media in human renal proximal tubular cells. Toxicol Sci. 2011, 119(2): 408-416.

44.Andreucci M, Fuiano G, Presta P, Esposito P, Faga T et al. Radiocontrast media cause dephosphorylation of Akt and downstream signaling targets in human renal proximal tubular cells. Biochem Pharmacol. 2006, 72(10): 1334-1342.

45.Andreucci M, Faga T, Russo D, Bertucci B, Tamburrini O et al. Differential activation of signaling pathways by low-osmolar and iso-osmolar radiocontrast agents in human renal tubular cells. J Cell Biochem. 2014, 115(2): 281-289.

46.Ronda N, Poti F, Palmisano A, Gatti R, Orlandini G et al. Effects of the radiocontrast agent iodixanol on endothelial cell morphology and function. Vascul Pharmacol. 2013, 58(1-2): 39-47.

47.Franke RP, Fuhrmann R, Hiebl B, Jung F. Influence of radiographic contrast media (iodixanol und iomeprol) on the morphology of human arterial and venous endothelial cells on extracellular matrix in vitro. Clin Hemorheol Microcirc. 2011, 48(1): 41-56.

48.Sendeski MM, Persson AB, Liu ZZ, Busch JF, Weikert S et al. Iodinated contrast media cause endothelial damage leading to vasoconstriction of human and rat vasa recta. Am J Physiol Renal Physiol. 2012, 303(12): F1592-F1598.

49.Michael A, Faga T, Pisani A, Riccio E, Bramanti P et al. Molecular mechanisms of renal cellular nephrotoxicity due to radiocontrast media. Biomed Res Int. 2014, 2014: 249810.

50.Andreucci M. [Contrast media and nephrotoxicity: a molecular conundrum]. G Ital Nefrol. 2011, 28(4): 355.

51.Andreucci M, Michael A, Kramers C, Park KM, Chen A et al. Renal ischemia/reperfusion and ATP depletion/repletion in LLC-PK(1) cells result in phosphorylation of FKHR and FKHRL1. Kidney Int. 2003, 64(4): 1189-1198.

52.Andreucci M, Fuiano G, Presta P, Lucisano G, Leone F et al. Downregulation of cell survival signalling pathways and increased cell damage in hydrogen peroxide-treated human renal proximal tubular cells by alpha-erythropoietin. Cell Prolif. 2009, 42(4): 554-561.

53.Andreucci M, Faga T, Lucisano G, Uccello F, Pisani A et al. Mycophenolic acid inhibits the phosphorylation of NF-kappaB and JNKs and causes a decrease in IL-8 release in H2O2-treated human renal proximal tubular cells. Chem Biol Interact. 2010, 185(3): 253-262.

54.Persson PB, Hansell P, Liss P. Pathophysiology of contrast medium-induced nephropathy. Kidney Int. 2005, 68(1): 14-22.

55.Singh J, Daftary A. Iodinated contrast media and their adverse reactions. J Nucl Med Technol. 2008, 36(2): 69-74.

56.Cunha MA, Schor N. Effects of gentamicin, lipopolysaccharide, and contrast media on immortalized proximal tubular cells. Ren Fail. 2002, 24(6): 687-690.

57.Peer A, Averbukh Z, Berman S, Modai D, Averbukh M et al. Contrast media augmented apoptosis of cultured renal mesangial, tubular, epithelial, endothelial, and hepatic cells. Invest Radiol. 2003, 38(3): 177-182.

58.Haller C, Hizoh I. The cytotoxicity of iodinated radiocontrast agents on renal cells in vitro. Invest Radiol. 2004, 39(3): 149-154.

59.McCullough PA. Acute kidney injury with iodinated contrast. Crit Care Med. 2008, 36(4 Suppl): S204-S211.

60.Weisbord SD. Iodinated contrast media and the kidney. Rev Cardiovasc Med. 2008, 9 Suppl 1: S14-S23.

61.Franke RP, Scharnweber T, Fuhrmann R, Wenzel F, Kruger A, Mrowietz C et al. Effect of radiographic contrast media on the spectrin/band3-network of the membrane skeleton of erythrocytes. PLoS One. 2014, 9(2): e89512.

62.Katzberg RW. Urography into the 21st century: new contrast media, renal handling, imaging characteristics, and nephrotoxicity. Radiology. 1997, 204(2): 297-312.

63.Aspelin P, Aubry P, Fransson SG, Strasser R, Willenbrock R et al. Nephrotoxic effects in high-risk patients undergoing angiography. N Engl J Med. 2003, 348(6): 491-499.

64.Taliercio CP, Vlietstra RE, Ilstrup DM, Burnett JC, Menke KK et al. A randomized comparison of the nephrotoxicity of iopamidol and diatrizoate in high risk patients undergoing cardiac angiography. J Am Coll Cardiol. 1991, 17(2): 384-390.

65.Barrett BJ, Carlisle EJ. Metaanalysis of the relative nephrotoxicity of high- and low-osmolality iodinated contrast media. Radiology. 1993, 188(1): 171-178.

66.Barrett BJ. Contrast nephrotoxicity. J Am Soc Nephrol. 1994, 5(2): 125-137.

67.Heinrich MC, Haberle L, Muller 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(1): 68-86.

68.Solomon RJ, Natarajan MK, Doucet S, Sharma SK, Staniloae CS et al. 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(25): 3189-3196.

69.Reed M, Meier P, Tamhane UU, Welch KB, Moscucci M et al. The relative renal safety of iodixanol compared with low-osmolar contrast media: a meta-analysis of randomized controlled trials. JACC Cardiovasc Interv. 2009, 2(7): 645-654.

70.Bolognese L, Falsini G, Schwenke C, Grotti S, Limbruno U et al. Impact of iso-osmolar versus low-osmolar contrast agents on contrast-induced nephropathy and tissue reperfusion in unselected patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention (from the Contrast Media and Nephrotoxicity Following Primary Angioplasty for Acute Myocardial Infarction [CONTRAST- AMI] Trial). Am J Cardiol. 2012, 109(1): 67-74.

71.Chalmers N, Jackson RW. Comparison of iodixanol and iohexol in renal impairment. Br J Radiol. 1999, 72(859): 701- 703.

72.Nguyen SA, Suranyi P, Ravenel JG, Randall PK, Romano PB et al. Iso-osmolality versus low-osmolality iodinated contrast medium at intravenous contrast-enhanced CT: effect on kidney function. Radiology. 2008, 248(1): 97-105.

73.Seeliger E, Lenhard DC, Persson PB. Contrast Media Viscosity versus Osmolality in Kidney Injury: Lessons from Animal Studies. Biomed Res Int. 2014, 2014: 358136.

74.Jost G, Pietsch H, Sommer J, Sandner P, Lengsfeld P et al. Retention of iodine and expression of biomarkers for renal damage in the kidney after application of iodinated contrast media in rats. Invest Radiol. 2009, 44(2): 114-123.

75.Dyvik K, Dyrstad K, Tronstad A. Relationship between viscosity and determined injection pressure in angiography catheters for common roentgen contrast media. Acta Radiol Suppl. 1995, 399: 43-49.

76.Thomsen HS, Morcos SK. Contrast media and the kidney: European Society of Urogenital Radiology (ESUR) guidelines. Br J Radiol. 2003, 76(908): 513-518.

77.Morcos SK, Thomsen HS, Webb JA. Contrast-media-induced nephrotoxicity: a consensus report. Contrast Media Safety Committee, European Society of Urogenital Radiology (ESUR). Eur Radiol. 1999, 9(8): 1602-1613.

78.Toprak O. Conflicting and new risk factors for contrast induced nephropathy. J Urol. 2007, 178(6): 2277-2283.

79.Pakfetrat M, Nikoo MH, Malekmakan L, Tabande M, Roozbeh J et al. Comparison of risk factors for contrast-induced acute kidney injury between patients with and without diabetes. Hemodial Int. 2010, 14(4): 387-392.

80.Schoolwerth AC, Sica DA, Ballermann BJ, Wilcox CS, Council on the Kidney in Cardiovascular D and the Council for High Blood Pressure Research of the American Heart A. Renal considerations in angiotensin converting enzyme inhibitor therapy: a statement for healthcare professionals from the Council on the Kidney in Cardiovascular Disease and the Council for High Blood Pressure Research of the American Heart Association. Circulation. 2001, 104(16): 1985-1991.

81.Morcos SK. Contrast media-induced nephrotoxicity--questions and answers. Br J Radiol. 998, 71(844): 357-365.

82.Kolonko A, Kokot F, Wiecek A. Contrast-associated nephropathy-- old clinical problem and new therapeutic perspectives. Nephrol Dial Transplant. 1998, 13: 803-806.

83.Neyra JA, Shah S, Mooney R, Jacobsen G, Yee J et al. Contrast- induced acute kidney injury following coronary angiography: a cohort study of hospitalized patients with or without chronic kidney disease. Nephrol Dial Transplant. 2013, 28: 1463-1471.

84.Cirit M, Toprak O, Yesil M, Bayata S, Postaci N et al. Angiotensin- converting enzyme inhibitors as a risk factor for contrast- induced nephropathy. Nephron Clin Pract. 2006, 104(1): c20-c27.

85.Kiski D, Stepper W, Brand E, Breithardt G, Reinecke H. Impact of renin-angiotensin-aldosterone blockade by angiotensin- converting enzyme inhibitors or AT-1 blockers on frequency of contrast medium-induced nephropathy: a post-hoc analysis from the Dialysis-versus-Diuresis (DVD) trial. Nephrol Dial Transplant. 2010, 25(3): 759-764.

86.Rim MY, Ro H, Kang WC, Kim AJ, Park H et al. The effect of renin- angiotensin-aldosterone system blockade on contrast-induced acute kidney injury: a propensity-matched study. Am J Kidney Dis. 2012, 60(4): 576-582.

87.Umruddin Z, Moe K, Superdock K. ACE inhibitor or angiotensin II receptor blocker use is a risk factor for contrast-induced nephropathy. J Nephrol. 2012, 25(5): 776-781.

88.Onuigbo MA, Onuigbo NT. Does renin-angiotensin aldosterone system blockade exacerbate contrast-induced nephropathy in patients with chronic kidney disease? A prospective 50-month Mayo Clinic study. Ren Fail. 2008, 30(1): 67-72.

89.Rosenstock JL, Bruno R, Kim JK, Lubarsky L, Schaller R et al. 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(3): 749-755.

90.Group KDIGOKAKIW. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int. 2012, 2: 1-138

91.Barrett BJ, Parfrey PS. Prevention of nephrotoxicity induced by radiocontrast agents. N Engl J Med. 1994, 331(21): 1449-1450.

92.Andreucci M, Federico S, Andreucci VE. Edema and acute renal failure. Semin Nephrol. 2001, 21(3): 251-256.

93.Andreucci VE, Russo D, Cianciaruso B, Andreucci M. Some sodium, potassium and water changes in the elderly and their treatment. Nephrol Dial Transplant 11 Suppl. 1996, 9: 9-17.

94.Andreucci M, Faga T, Sabbatini M, Pisani A, Russo D et al. How to prevent Contrast-Induced Nephropathy in clinical practice. J Clin Nephrol Res. 2014, 1(1): 1002.

95.Ad-hoc working group of E, Fliser D, Laville M, Covic A, Fouque D et al. A European Renal Best Practice (ERBP) position statement on the Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guidelines on acute kidney injury: part 1: definitions, conservative management and contrast-induced nephropathy. Nephrol Dial Transplant. 2012, 27(12): 4263-4272.

96.Thomson K. Safe use of radiographic contrast media. Aust Prescr. 2010, 33: 19-22.

97.Keaney JJ, Hannon CM, Murray PT. Contrast-induced acute kidney injury: how much contrast is safe? Nephrol Dial Transplant. 2013, 28(6): 1376-1383.

98.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(6 Pt 1): 649-652.

99.Laskey WK, Jenkins C, Selzer F, Marroquin OC, Wilensky RL et al. Volume-to-creatinine clearance ratio: a pharmacokinetically based risk factor for prediction of early creatinine increase after percutaneous coronary intervention. J Am Coll Cardiol. 2007, 50(7): 584-590.

100.Gurm HS, Dixon SR, Smith DE, Share D, Lalonde T et al. Renal function-based contrast dosing to define safe limits of radiographic contrast media in patients undergoing percutaneous coronary interventions. J Am Coll Cardiol. 2011, 58(9): 907-914.

101.Mueller C. Prevention of contrast-induced nephropathy with volume supplementation. Kidney Int Suppl. 2006, (100): S16-S19.

102.Balemans CE, Reichert LJ, van Schelven BI, van den Brand JA, Wetzels JF. Epidemiology of contrast material-induced nephropathy in the era of hydration. Radiology. 2012, 263: 706- 713.

103.Thomsen HS. Guidelines for contrast media from the European Society of Urogenital Radiology. AJR Am J Roentgenol. 2003, 181(6): 1463-1471.

104.Ellis JH, Cohan RH. Prevention of contrast-induced nephropathy: an overview. Radiol Clin North Am. 2009, 47(5): 801-811.

105.Solomon R, Dauerman HL. Contrast-induced acute kidney injury. Circulation. 2010, 122(23): 2451-2455.

106.Merten GJ, Burgess WP, Gray LV, Holleman JH, Roush TS et al. Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial. JAMA. 2004, 291(19): 2328-2334.

107.Masuda M, Yamada T, Mine T, Morita T, Tamaki S et al. Comparison of usefulness of sodium bicarbonate versus sodium chloride to prevent contrast-induced nephropathy in patients undergoing an emergent coronary procedure. Am J Cardiol. 2007, 100(5): 781-786.

108.Ozcan EE, Guneri S, Akdeniz B, Akyildiz IZ, Senaslan O et al. Sodium bicarbonate, N-acetylcysteine, and saline for prevention of radiocontrast-induced nephropathy. A comparison of 3 regimens for protecting contrast-induced nephropathy in patients undergoing coronary procedures. A single-center prospective controlled trial. Am Heart J. 2007, 154(3): 539-544.

109.Tamura A, Goto Y, Miyamoto K, Naono S, Kawano Y et al. Efficacy of single-bolus administration of sodium bicarbonate to prevent contrast-induced nephropathy in patients with mild renal insufficiency undergoing an elective coronary procedure. Am J Cardiol. 2009, 104(7): 921-925.

110.Navaneethan SD, Singh S, Appasamy S, Wing RE, Sehgal AR. Sodium bicarbonate therapy for prevention of contrast-induced nephropathy: a systematic review and meta-analysis. Am J Kidney Dis. 2009, 53(4): 617-627.

111.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(3): 747-758.

112.Joannidis M, Schmid M, Wiedermann CJ. Prevention of contrast media-induced nephropathy by isotonic sodium bicarbonate: a meta-analysis. Wien Klin Wochenschr. 2008, 120(23-24): 742-748.

113.Assadi F. Acetazolamide for prevention of contrast-induced nephropathy: a new use for an old drug. Pediatr Cardiol. 2006, 27(2): 238-242.

114.Pakfetrat M, Nikoo MH, Malekmakan L, Tabandeh M, Roozbeh J et al. A comparison of sodium bicarbonate infusion versus normal saline infusion and its combination with oral acetazolamide for prevention of contrast-induced nephropathy: a randomized, double-blind trial. Int Urol Nephrol. 2009, 41(3): 629-634.

115.Reddan D, Laville M, Garovic VD. Contrast-induced nephropathy and its prevention: What do we really know from evidence-based findings? J Nephrol. 2009, 22(3): 333-351.

116.Zoungas S, Ninomiya T, Huxley R, Cass A, Jardine M et al. Systematic review: sodium bicarbonate treatment regimens for the prevention of contrast-induced nephropathy. Ann Intern Med. 2009, 151(9): 631-638.

117.Sardella G, Briguori C, Garbo R, Romagnoli E, Pennacchi M et al. Evidence from the Resorbable-polymer stent versus Unresorbable- polymer stent Deployment for coronary Intervention: (RUDI-2) registry. Int J Cardiol. 2014, 172(2): 472-475.

118.Safirstein R, Andrade L, Vieira JM. Acetylcysteine and nephrotoxic effects of radiographic contrast agents--a new use for an old drug. N Engl J Med. 2000, 343(3): 210-212.

119.Lee HC, Sheu SH, Liu IH, Lee CC, Hsieh CC et al. Impact of short-duration administration of N-acetylcysteine, probucol and ascorbic acid on contrast-induced cytotoxicity. J Nephrol. 2012, 25(1): 56-62.

120.DiMari J, Megyesi J, Udvarhelyi N, Price P, Davis R et al. N-acetyl cysteine ameliorates ischemic renal failure. Am J Physiol. 1997, 272(3Pt 2): F292-F298.

121.Tepel M, van der Giet M, Schwarzfeld C, Laufer U, Liermann D et al. Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine. N Engl J Med. 2000, 343(3): 180-184.

122.Baker CS, Wragg A, Kumar S, De Palma R, Baker LR et al. A rapid protocol for the prevention of contrast-induced renal dysfunction: the RAPPID study. J Am Coll Cardiol. 2003, 41(12): 2114-2118.

123.Durham JD, Caputo C, Dokko J, Zaharakis T, Pahlavan M et al. A randomized controlled trial of N-acetylcysteine to prevent contrast nephropathy in cardiac angiography. Kidney Int. 2002, 62(6): 2202-2207.

124.Allaqaband S, Tumuluri R, Malik AM, Gupta A, Volkert P et al. Prospective randomized study of N-acetylcysteine, fenoldopam, and saline for prevention of radiocontrast-induced nephropathy. Catheter Cardiovasc Interv. 2002, 57(3): 279-283.

125.Goldenberg I, Shechter M, Matetzky S, Jonas M, Adam M et al. Oral acetylcysteine as an adjunct to saline hydration for the prevention of contrast-induced nephropathy following coronary angiography. A randomized controlled trial and review of the current literature. Eur Heart J. 2004, 25(3): 212-218.

126.Pannu N, Manns B, Lee H, Tonelli M. Systematic review of the impact of N-acetylcysteine on contrast nephropathy. Kidney Int. 2004, 65(4): 1366-1374.

127.Coyle LC, Rodriguez A, Jeschke RE, Simon-Lee A, Abbott KC et al. Acetylcysteine In Diabetes (AID): a randomized study of acetylcysteine for the prevention of contrast nephropathy in diabetics. Am Heart J. 2006, 151(5): 1032. e9-e12.

128.Ferrario F, Barone MT, Landoni G, Genderini A, Heidemperger M et al. Acetylcysteine and non-ionic isosmolar contrast- induced nephropathy--a randomized controlled study. Nephrol Dial Transplant. 2009, 24(10): 3103-3107.

129.Gurm HS, Smith DE, Berwanger O, Share D, Schreiber T et al. Contemporary use and effectiveness of N-acetylcysteine in preventing contrast-induced nephropathy among patients undergoing percutaneous coronary intervention. JACC Cardiovasc Interv. 2012, 5(1): 98-104.

130.Spargias K, Alexopoulos E, Kyrzopoulos S, Iokovis P, Greenwood DC et al. Ascorbic acid prevents contrast-mediated nephropathy in patients with renal dysfunction undergoing coronary angiography or intervention. Circulation. 2004, 110(18): 2837-2842.

131.Alexopoulos E, Spargias K, Kyrzopoulos S, Manginas A, Pavlides G et al. Contrast-induced acute kidney injury in patients with renal dysfunction undergoing a coronary procedure and receiving non-ionic low-osmolar versus iso-osmolar contrast media. Am J Med Sci. 2010, 339(1): 25-30.

132.Boscheri A, Weinbrenner C, Botzek B, Reynen K, Kuhlisch E et al. Failure of ascorbic acid to prevent contrast-media induced nephropathy in patients with renal dysfunction. Clin Nephrol. 2007, 68(5): 279-286.

133.Sadat U, Usman A, Gillard JH, Boyle JR. Does ascorbic acid protect against contrast-induced acute kidney injury in patients undergoing coronary angiography: a systematic review with meta-analysis of randomized, controlled trials. J Am Coll Cardiol. 2013, 62(23): 2167-2175.

134.Tasanarong A, Vohakiat A, Hutayanon P, Piyayotai D. New strategy of alpha- and gamma-tocopherol to prevent contrast- induced acute kidney injury in chronic kidney disease patients undergoing elective coronary procedures. Nephrol Dial Transplant. 2013, 28(2): 337-344.

135.Veverka A, Nuzum DS, Jolly JL. Nebivolol: a third-generation beta-adrenergic blocker. Ann Pharmacother. 2006, 40(7- 8): 1353-1360.

136.Toprak O, Cirit M, Tanrisev M, Yazici C, Canoz O et al. Preventive effect of nebivolol on contrast-induced nephropathy in rats. Nephrol Dial Transplant. 2008, 23(3): 853-859.

137.Avci E, Yesil M, Bayata S, Postaci N, Arikan E et al. The role of nebivolol in the prevention of contrast-induced nephropathy in patients with renal dysfunction. Anadolu Kardiyol Derg. 2011, 11(7): 613-617.

138.Gunebakmaz O, Kaya MG, Koc F, Akpek M, Kasapkara A et al. Does nebivolol prevent contrast-induced nephropathy in humans? Clin Cardiol. 2012, 35(4): 250-254.

139.Khanal S, Attallah N, Smith DE, Kline-Rogers E, Share D et al. Statin therapy reduces contrast-induced nephropathy: an analysis of contemporary percutaneous interventions. Am J Med. 2005, 118(8): 843-849.

140.Patti G, Nusca A, Chello M, Pasceri V, D'Ambrosio A et al. Usefulness of statin pretreatment to prevent contrast-induced nephropathy and to improve long-term outcome in patients undergoing percutaneous coronary intervention. Am J Cardiol. 2008, 101(3): 279-285.

141.Leoncini M, Toso A, Maioli M, Tropeano F, Bellandi F. Statin treatment before percutaneous cononary intervention. J Thorac Dis. 2013, 5(3): 335-342.

142.Zhang BC, Li WM, Xu YW. High-dose statin pretreatment for the prevention of contrast-induced nephropathy: a meta- analysis. Can J Cardiol. 2011, 27(6): 851-858.

143.Andreucci M. [Statins in CIN: a problem at least partly solved?]. G Ital Nefrol. 2013, 30(3).

144.Sabbatini M, Pisani A, Uccello F, Serio V, Seru R et al. Atorvastatin improves the course of ischemic acute renal failure in aging rats. J Am Soc Nephrol. 2004, 15(4): 901-909.

145.Yang D, Lin S, Yang D, Wei L, Shang W. Effects of short- and long-term hypercholesterolemia on contrast-induced acute kidney injury. Am J Nephrol. 2012, 35(1): 80-89.

146.Al-Otaibi KE, Al Elaiwi AM, Tariq M, Al-Asmari AK. Simvastatin attenuates contrast-induced nephropathy through modulation of oxidative stress, proinflammatory myeloperoxidase, and nitric oxide. Oxid Med Cell Longev. 2012, 2012: 831748.

147.Quintavalle C, Fiore D, De Micco F, Visconti G, Focaccio A et al. Impact of a high loading dose of atorvastatin on contrast- induced acute kidney injury. Circulation. 2012, 126(25): 3008-3016.

148.Acikel S, Muderrisoglu H, Yildirir A, Aydinalp A, Sade E et al. Prevention of contrast-induced impairment of renal function by short-term or long-term statin therapy in patients undergoing elective coronary angiography. Blood Coagul Fibrinolysis. 2010, 21(8): 750-757.

149.Patti G, Ricottini E, Nusca A, Colonna G, Pasceri V et al. 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): 1-7.

150.Heyman SN, Rosen S, Rosenberger C. Renal parenchymal hypoxia, hypoxia adaptation, and the pathogenesis of radiocontrast nephropathy. Clin J Am Soc Nephrol. 2008, 3(1): 288- 296.

151.Bucher AM, De Cecco CN, Schoepf UJ, Meinel FG, Krazinski AW et al. Is contrast medium osmolality a causal factor for contrast-induced nephropathy? Biomed Res Int. 2014, 2014: 931413.

152.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(21): 1416-1420.

153.Weinstein JM, Heyman S, Brezis M. Potential deleterious effect of furosemide in radiocontrast nephropathy. Nephron. 1992, 62(4): 413-415.

154.Weisberg LS, Kurnik PB, Kurnik BR. Risk of radiocontrast nephropathy in patients with and without diabetes mellitus. Kidney Int. 1994, 45(1):259-265.

155.Marenzi G, Ferrari C, Marana I, Assanelli E, De Metrio M et 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(1): 90-97.

156.Guastoni C, De Servi S, Covella P, Turri C, Gidaro B et al. [Prevention of contrast-induced acute kidney injury]. G Ital Nefrol 29 Suppl. 2012, 58: S33-S45.

157.Yang D, Yang D, Jia R, Tan J. Na+/Ca2+ exchange inhibitor, KB-R7943, attenuates contrast-induced acute kidney injury. J Nephrol. 1989, 26(5): 877-885.

158.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(12): 1030-1036.

159.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(3): 254-257.

160.Khoury Z, Schlicht JR, Como J, Karschner JK, Shapiro AP et al. The effect of prophylactic nifedipine on renal function in patients administered contrast media. Pharmacotherapy. 1995, 15(1): 59-65.

161.Spangberg-Viklund B, Berglund J, Nikonoff T, Nyberg P, Skau T et al. 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(1): 63-68.

162.Caiazza A, Russo L, Sabbatini M, Russo D. Hemodynamic and tubular changes induced by contrast media. Biomed Res Int. 2014, 2014: 578974.

163.Peguero JG, Cornielle V, Gomez SI, Issa OM, Heimowitz TB et al. The use of nitrates in the prevention of contrast-induced nephropathy in patients hospitalized after undergoing percutaneous coronary intervention. J Cardiovasc Pharmacol Ther. 2014, 19(3): 310-314.

164.Schindler R, Stahl C, Venz S, Ludat K, Krause W, Frei U. Removal of contrast media by different extracorporeal treatments. Nephrol Dial Transplant. 2001, 16(7): 1471-1474.

165.Lehnert T, Keller E, Gondolf K, Schaffner T, Pavenstadt H et al. Effect of haemodialysis after contrast medium administration in patients with renal insufficiency. Nephrol Dial Transplant. 1998, 13(2): 358-362.

166.Vogt B, Ferrari P, Schonholzer C, Marti HP, Mohaupt M et al. Prophylactic hemodialysis after radiocontrast media in patients with renal insufficiency is potentially harmful. Am J Med. 2001, 111(9): 692-698.

167.Esnault VL. Radiocontrast media-induced nephrotoxicity in patients with renal failure: rationale for a new double-blind, prospective, randomized trial testing calcium channel antagonists. Nephrol Dial Transplant. 2002, 17(8): 1362-1364.

168.Guastoni C, De Servi S, D'Amico M. The role of dialysis in contrast-induced nephropathy: doubts and certainties. J Cardiovasc Med (Hagerstown). 2007, 8(8): 549-557.

169.Lee PT, Chou KJ, Liu CP, Mar GY, Chen CL et al. Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis. A randomized controlled trial. J Am Coll Cardiol. 2007, 50(11): 1015-1020.

170.Marenzi G, Lauri G, Campodonico J, Marana I, Assanelli E et al. Comparison of two hemofiltration protocols for prevention of contrast-induced nephropathy in high-risk patients. Am J Med. 2006, 119(2): 155-162.

171.La Manna G, Pancaldi L, Dalmastri V, Cuna V, Capecchi A et al. Post-coronarography application of continuous veno-venous hemofiltration in the prevention of contrast nephropathy in patients with complex multisystem deficiency. In Vivo. 2008, 22(1): 123-129.

172.Guastoni C, Bellotti N, Poletti F, Covella P, Gidaro B et al. Continuous venovenous hemofiltration after coronary procedures for the prevention of contrast-induced acute kidney injury in patients with severe chronic renal failure. Am J Cardiol. 2014, 113(4): 588-592.

173.Pasternak JJ, Williamson EE. Clinical pharmacology, uses, and adverse reactions of iodinated contrast agents: a primer for the non-radiologist. Mayo Clin Proc. 2012, 87(4): 390-402.

Cite this article: Andreucci M. Radiographic contrast agents, drugs useful for diagnostics, but with contrast-induced nephropathy as side effect. J J Nephro Urol. 2015, 1(2): 13

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