*6.2.2 Theophylline*

Adenosine has been implicated to be a responsible factor for mediating CM-enhanced renal vasoconstriction [133–135]: hence the use of adenosine antagonists appears logical [136]. Theophylline and aminophylline have been often used to measure their efficacy as adenosine receptor antagonists in guarding against contrast-induced acute kidney injury (CI-AKI). Various randomized trials have used theophylline [20, 137, 138]. A meta-analysis of those studies guided to the fact that theophylline considerably lowers the risk of CIN (RR: 0.48; 95% CI: 0.26–0.89; p = 0.02). There was moderate heterogeneity that suggests cautious interpretation of these results. Furthermore, patients with baseline renal insufficiency did not show any benefit from theophylline.

### *6.2.3 Allopurinol*

This drug is a xanthine oxidase inhibitor which may hamper the fall in the GFR following CM exposure by limiting oxygen free radical production, inhibiting adenine nucleotide degradation, and limiting the vasodilator reaction to intrarenal adenosine. A trial that included 159 patients randomized patients performing coronary angiography procedures to allopurinol (300 mg orally) with hydration or hydration alone, showed that allopurinol can guard against CIN in high-risk patients receiving CM [139]. However, these effects of allopurinol in the prevention of CIN need further larger studies.

#### *6.2.4 Dopamine*

Dopamine (in a renal dose 0.5–2.5 μg/kg/min) has a vasodilator action on the renal vasculature and has an ability to increase renal blood flow and GFR with a potential benefit in the prevention of CIN. Trials with positive results were small, not randomized and with questionable endpoints [140]. On the contrary, negative trials were large, randomized, controlled, and with adequate statistical power [141]. Thus, the usage of dopamine in guarding against CIN is no longer recommended.

#### *6.2.5 Targeted renal therapy*

A suggested theory for failure of various drugs used for kidney protection is that systemically administered drugs may not achieve adequate drug level in the renal vasculature in order to be successful regarding the prevention of CIN. This has led to the technique of direct infusion of a drug in a selective manner into the kidneys via the renal arteries, which is known as targeted renal therapy (TRT). This should have the ability of decreasing the systemic side effects of that drug. Fenoldopam is a dopamine-1 agonist that acts as a vasodilator and thus has a potential to attenuate the vasoconstriction induced by CM in the renal vessels. Although it was not possible to demonstrate its benefit in reducing the incidence of CIN [142], it was observed that a large number of patients could not tolerate low doses of fenoldopam as a result of drug-induced hypotension, which is itself a risk predictor of CIN. Employing TRT, selective bilateral renal artery catheterization may be performed for localized drug delivery. In a pilot study on patients undergoing endovascular aneurysm repair, Benephit PV Infusion System (Flow Medica, Inc., Fremont, CA, USA) was used for selective catheterization of both renal arteries through brachial artery puncture. There was no episode of hypotension, thus every patient received fenoldopam at a rate of 0.4μg/kg/min for the duration of the aneurysm repair [143]. If the pigtail catheter is inserted in the aorta just over the level of the renal artery avoiding selective catheterization, this appears to be a simple way but would lead to considerable systemic drug effects as a result of infusion of the drug into the systemic circulation [143]. The safety and performance of TRT were also assessed by retrospective analysis of 285 patients who received fenoldopam via TRT, as a part of "The Benephit System Renal Infusion Therapy (Be-RITe)" registry [144]. Benephit Infusion System (Flow Medica, Inc., Fremont, CA, USA) was used. Bilateral renal artery cannulation achieved success in 94.2%, with a mean cannulation time of 2min. Incidence of CIN was 71% less than predicted, with the greatest

**131**

this case.

**8. Conclusion**

*Contrast-Induced Nephropathy*

*6.2.6 Ischemic preconditioning*

**7. Sequelae**

*DOI: http://dx.doi.org/10.5772/intechopen.90457*

benefit in patients with highest risk of CIN. Prospective studies and RCTs are

Ischemic preconditioning includes exposure to short episodes of ischemia followed by reperfusion to make the target organ prepared against the main ischemic insult. If the site of generation of these short episodes of ischemic reperfusion is remote from the site of target organ, it is called remote ischemic preconditioning. This technique has been used with only variable success in offering myocardial and renal protection in cardiovascular medicine [145–151]. Results of an RCT propose usefulness from remote ischemic preconditioning in preventing CIN [152]. The likely usefulness may arise from its capability to attenuate the CM-induced ischemia reperfusion injury. Recently, ischemic preconditioning has lost its credibility as it was unable to translate successful results in laboratories into clinical practice [153].

Patients who develop CIN have greater complications, a worse prognosis, more serious long-term outcomes, and longer duration of hospital stay, which result in elevated medical costs [154, 155]. Less than 0.5–2% of patients who develop CIN require dialysis [156]. Those requiring dialysis are more likely to exhibit serious short- and long-term outcomes. Nearly 30% of those patients experience chronic renal impairment [154]. CIN may also be linked to an increased mortality which is independent of other risk factors [157]. Hospital death rates in such patients have been reported as 36% and the 2-year survival rate as only 19% [158, 159]. Levy et al. compared 181 inpatients that developed CIN with matched control patients who did not develop it; both groups underwent contrast-related procedures [156]. The mortality rate in the control group was 7%, compared to 34% in the CIN group. In another study of 7230 patients who underwent percutaneous coronary interventions, patients who developed CIN had more common myocardial infarctions, more hospital stays, and higher 1-year mortality rates compared to those without CIN. CIN patients are more likely to have target vessel revascularization after 1 year, bypass surgery, bleeding which mandates transfusion, and various vascular complications [160]. Patients who undergo a primary percutaneous intervention for acute myocardial infarction and the procedure complicates by CIN were reported to be significantly more likely to have major complications within hospital admission such as acute pulmonary edema, the need for pacemaker insertion, cardiogenic shock, and respiratory failure [160]. Patients with renal insufficiency are at more significant risk of developing atherosclerosis [19]. Actually, following a contrast procedure, a rise in serum creatinine is a more significant indicator of late mortality

therefore required in order to assess real ability of this technique.

compared to an elevated creatine kinase-MB isoenzyme [160].

Contrast-induced nephropathy is a not an uncommon sequela of coronary angioplasty. It can lead to increased morbidity and mortality. One should be aware of the risk factors that increase its incidence and thus limit the amount of contrast so as to avoid such a deleterious complication. Prevention is better than treatment in benefit in patients with highest risk of CIN. Prospective studies and RCTs are therefore required in order to assess real ability of this technique.
