*6.1.2 Oral hydration*

In order to overcome the limitations of outpatient intravenous hydration, investigators have assessed the use of pre-procedure oral hydration followed by postprocedure intravenous hydration in patients who are admitted for catheterization on the day of procedure. In an RCT on patients with mild-to-moderate renal insufficiency, Taylor et al. reported an effective protocol which includes pre-angiography oral hydration (1000mL clear fluids over 10h) that is followed by 6h of intravenous hydration (0.45% normal saline solution at 300mL/h) that starts just before CM

**127**

*Contrast-Induced Nephropathy*

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

saline hydration as regards preventing CI-AKI.

*6.1.3 Sodium bicarbonate-based hydration*

efficacious to saline hydration only.

*6.1.4 Pharmacological prophylaxis*

exposure [69]. The results were comparative with overnight intravenous hydration (0.45% normal saline solution at 75mL/h for both 12h before and after angiography). A limitation of this protocol can be high infusion rate (300mL/h) post-procedure for the patients having left ventricular impairment. Trivedi and his colleagues demonstrated different results as they observed that patients with unrestricted oral hydration had more opportunities of acute renal impairment compared to those receiving normal saline for 24h (at a rate of 1mL/kg/h) beginning 12h before the scheduled catheterization (p = 0.005) [68]. In this study, however, there was no set protocol for oral hydration for patients to follow that probably could have contributed to its ineffectiveness. Later, Dussol et al. randomized 312 patients with chronic kidney disease (CKD) to receive either per oral sodium chloride (NaCl) (dose: 1g/10kg bodyweight/day for 2 days before the procedure), intravenous normal saline 15mL/kg for the 6h preceding the procedure (control arm), theophylline, or furosemide in addition to the treatment given to patients in the control arm [70]. Oral saline hydration was found to have comparative effectiveness as intravenous

The acidic PH promotes free radical production (which is found in tubular urine) [71], while elevated pH of normal extracellular fluid inhibits it [72, 73]. Since CM administration escalates the oxidative stress and increases the generation of free radicals and reactive oxygen species (ROS), alkalinizing renal tubular fluid with bicarbonate appears to be a logical strategy to protect against renal injury [74]. As a result of active reabsorption, bicarbonate concentration in the renal tubules lowers (to about 6mEq/L), and the tubular fluid pH is approximately 6.5 near the end of the proximal tubule in the renal medulla [75]. In the descending loop of Henle, water and chloride are passively reabsorbed. This elevates urine pH to ~7.4 at the tip of the papilla, and this part is spared from contrast nephropathy [76], which suggests that higher pH is protective. Also important is the observation that outer medulla is the most susceptible to CIN [62] and has acidic pH [72] that promotes activity of ROS. Superoxide, a ROS generated by ischemia, might react with medullary NO to produce the potent oxidant peroxynitrite [73]. At physiologic concentrations, bicarbonate scavenges peroxynitrite and other ROSs produced from NO [74]. Thus, several oxidant mechanisms of renal injury might be avoided using sodium bicarbonate. The useful effect of higher proximal tubular pH is approved by a report that acetazolamide, a carbonic-anhydrase inhibitor which blocks proximal tubular bicarbonate reabsorption, is protective in contrast-induced renal failure [77]. Merten et al. reported first study on the use of sodium bicarbonate in humans as a nephron-protective agent [78]. Patients received 154mEq/l of either NaCl (in 5% dextrose H2O) or sodium bicarbonate (in dextrose H2O), as a bolus of 3mL/kg/h for 1h before iopamidol contrast, followed by an infusion of 1mL/kg/h for 6h after the procedure. CIN occurred in 8 patients (13.6%) infused with NaCl but in only 1 (1.7%) of those receiving sodium bicarbonate (p = 0.02). Afterwards, many RCTs have compared the efficacy of sodium bicarbonate with saline hydration regarding the prophylaxis against CIN. These have been reviewed in multiple meta-analysis [79–82], which concluded that sodium bicarbonate-based saline hydration is more

Various drugs have been assessed as prophylactic nephroprotective agents against contrast-induced acute kidney injury (CI-AKI) such as N-acetylcysteine

#### *Contrast-Induced Nephropathy DOI: http://dx.doi.org/10.5772/intechopen.90457*

*New Insight into Cerebrovascular Diseases - An Updated Comprehensive Review*

Among the often-discussed mechanisms, superoxide and other reactive oxygen species (ROS) have been discussed to be an aggravating factor for CIN. Oxygen free radicals are endogenously produced, and levels can increase during oxidative stress.

and OH−

dismutase. In these models, CM-induced reductions in glomerular filtration rate are

Adequate hydration for patients performing CM-enhanced imaging studies was suggested approximately 40years ago [30]. The beneficial effects of hydration were initially reported in the early 1980s by studies that compared outcomes of hydrated patients with historical controls [60, 61]. These reports were supported by the first RCT in 1994, concluding that patients with chronic renal impairment benefit better from intravenous (0.45%) saline administration (for 12h before and 12h after angiography) in comparison with saline plus mannitol or furosemide [62]. Since then, multiple RCTs have assured the benefit of intravenous normal saline (0.9%) hydration that is started 12h preceding to 12h after CM injection [63–65] in the prevention against CIN over 0.45% saline [65] or a fluid bolus (300mL) during CM administration only [66]. The rate of infusion was reported as 1mL/kg/h [67]. CM safety committee endorse a regime of intravenous infusion of 1.0–1.5mL/kg/h for at

In order to overcome the limitations of outpatient intravenous hydration, investigators have assessed the use of pre-procedure oral hydration followed by postprocedure intravenous hydration in patients who are admitted for catheterization on the day of procedure. In an RCT on patients with mild-to-moderate renal insufficiency, Taylor et al. reported an effective protocol which includes pre-angiography oral hydration (1000mL clear fluids over 10h) that is followed by 6h of intravenous hydration (0.45% normal saline solution at 300mL/h) that starts just before CM

**6. Preventive measures against contrast-induced nephropathy**

with H2O2, which is not a radical but shows greater membrane permeability. O2

rapidly scavenges nitric oxide (NO) and could diminish NO activity in the renal vessels. Since NO decreases oxygen consumption, it is considerable to speculate that decreased (scavenged) NO levels in diabetes increases oxygen consumption, thus leading to reduced partial oxygen pressure values with consequences for endothelial-epithelial structure and function. ROS can play a role in the effects of various vasoconstrictors that are considered necessary for the development of CIN. Because ROS are extracellular signaling molecules, they can have a crucial role in mediating the effects of vasoconstrictors, such as thromboxane A2, angiotensin II, adenosine, endothelin (ET)-1, and norepinephrine. The adverse effects of CM on kidney function can therefore involve the generation of ROS, for example, via adenosine formation. This idea is supported by experiments in which the generation of ROS was inhibited by allopurinol or the amount of ROS was decreased by O2

−

), hydrogen peroxide (H2O2),

−

−

are more reactive in comparison

**5.4 Generation of oxygen-free radicals**

and hydroxyl radical (OH<sup>−</sup>

attenuated [59].

**6.1 Adequate hydration**

*6.1.1 Intravenous hydration*

*6.1.2 Oral hydration*

least 6h before and after CM administration [68].

The commonest oxygen radicals are superoxide (O2

) [58]. O2

−

**126**

exposure [69]. The results were comparative with overnight intravenous hydration (0.45% normal saline solution at 75mL/h for both 12h before and after angiography). A limitation of this protocol can be high infusion rate (300mL/h) post-procedure for the patients having left ventricular impairment. Trivedi and his colleagues demonstrated different results as they observed that patients with unrestricted oral hydration had more opportunities of acute renal impairment compared to those receiving normal saline for 24h (at a rate of 1mL/kg/h) beginning 12h before the scheduled catheterization (p = 0.005) [68]. In this study, however, there was no set protocol for oral hydration for patients to follow that probably could have contributed to its ineffectiveness. Later, Dussol et al. randomized 312 patients with chronic kidney disease (CKD) to receive either per oral sodium chloride (NaCl) (dose: 1g/10kg bodyweight/day for 2 days before the procedure), intravenous normal saline 15mL/kg for the 6h preceding the procedure (control arm), theophylline, or furosemide in addition to the treatment given to patients in the control arm [70]. Oral saline hydration was found to have comparative effectiveness as intravenous saline hydration as regards preventing CI-AKI.
