**4.11 Nephrotoxic drugs**

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

tensin converting enzyme (ACE) inhibitors [30].

chronic kidney disease (OR = 0.95, p < 0.00001) [17].

nitric oxide synthesis that provokes the development of CIN [32].

Advanced congestive heart failure (New York Heart Association class III or IV), reduced left ventricular ejection fraction, or any history of congestive heart failure are independent predictors of CIN and contribute to a greater risk in patients who have diabetes or renal disease. The risk arises as a result of decreased renal blood flow due to low cardiac output in those patients. Moreover, the risk is enhanced by this population's use of specific medications such as aspirin, diuretics, and angio-

Anemia can cause deterioration of renal ischemia which can be an acceptable explanation for the higher incidence of contrast-induced nephropathy in patients with a lower hematocrit level. A baseline hematocrit value of less than 39% for men and less than 36% for women is considered a risk that leads to a higher incidence of CIN. This relation was investigated in a prospective study of 6773 patients who underwent PCI [31]. A lower basal hematocrit value was an independent risk predictor of CIN; and every 3% decline in basal hematocrit resulted in a significant increase in the occurrence of CIN in patients with and without chronic kidney disease (11 and 23%, respectively). Dangas et al. showed that the basal hematocrit level is an independent risk factor for the occurrence of CIN among patients with

Contrast media have a uricosuric effect, which is caused by increased renal tubular secretion of uric acid. Moreover, hyperuricemia is accompanied by an activated renin-angiotensin-aldosterone system, enhanced synthesis of reactive oxygen species, increased endothelin-1, tubular obstruction by uric acid, and an inhibited

Altered nitric oxide-dependent renal vasodilatation is common in hypercholesterolemia. Hypercholesterolemia enhanced the occurrence of CIN through the

Hypovolemia leads to active sodium reabsorption, which is an oxygen-dependent process, and increases neurohumoral vasoconstrictive stimuli that can diminish medullary oxygenation. The toxic actions of contrast media on the renal tubular lumen can be exaggerated in hypovolemia. Decreased circulatory volume and renal perfusion augment vasoconstriction of renal vasculature after administration of CM. Volume expansion decreases the activity of the renin-angiotensin system, increases the perfusion of the medulla, and minimizes the elevation in blood viscosity and osmolality. Currently, the most effective preventive measure against the

The alteration in intrarenal expression of vasoactive mediators, mainly reninangiotensin system and nitric oxide, is a common cause that ranks hypertension as

**4.5 Heart failure**

**4.6 Anemia**

**4.7 Hyperuricemia**

**4.8 Hypercholesterolemia**

**4.9 Hypovolemia**

**4.10 Hypertension**

reduced production of nitric oxide [24].

development of CIN is proper hydration [33].

**122**

Nephrotoxic drugs that inhibit the vasodilatory effects of prostaglandins make the kidneys extremely vulnerable to the toxic effect of contrast media. Aminoglycosides, sulfonamides, and their combinations with furosemide are very risky. Cyclosporin A may intensify medullary hypoxia, and cisplatin can bind to sulfhydryl groups. Mannitol can increase the metabolic load and the oxygen consumption of the kidney, and amphotericin B can cause the combined effect of mannitol and cyclosporine A. It has been demonstrated that nonselective NSAIDs and selective COX-2 inhibitors decrease the availability of vasodilatory prostaglandins in the kidneys and enhance the vasoconstrictive effect of CM [34].
