Iodinated contrast media are a frequent cause of acute renal failure, especially in patients whose renal function is already impaired. In addition to hydration, which remains the most commonly acknowledged means of protection, numerous pharmacological approaches for the prophylaxis of contrast nephropathy have been tested so far. They include diuretics, calcium channel blockers, adenosine receptor antagonists, N-acetylcysteine, low-dose dopamine and the dopamine D1 receptor agonist fenoldopam, endothelin receptor antagonists, and even captopril. The present review of the literature critically discusses the drugs used to prevent contrast nephropathy from a pharmacological point of view.
Iodinated contrast media (CM)-induced nephropathy is a serious complication of diagnostic or interventional procedures. It basically occurs in at-risk patients (especially patients with chronic renal insufficiency, associated or not with diabetes mellitus).1,2 Although generally mild, it can result in the need for dialysis, in prolonged hospitalization, and increased morbidity and mortality.3,4 It is now widely acknowledged that high-osmolality CM (ionic) are more nephrotoxic than low-osmolality CM, ionic or nonionic5, in at-risk patients. It is also classically recognized that CM can induce an imbalance between a decreased oxygen supply to the medulla and an increased workload associated with the filtration of the compound, which can be deleterious in patients with already impaired renal function.2 CM induce both direct cytotoxic insults and renal vasoconstriction (Fig. 1). Irrespective of the mechanism of CM-induced nephropathy, hydration remains the most commonly acknowledged means of protection against CM-induced nephropathy (CIN).1,2,6 Animal studies7,8 and several observations comparing well-hydrated patients with a historical population9,10 are at the root of the general acknowledgment of extracellular volume expansion as a means of preventing CIN. Conversely, dehydration before the procedure has been shown to enhance the risk of CIN,11,12 thus providing an a contrario proof. Various protocols can be found in the literature, including the use of 0.45% saline to produce both volume expansion and a large volume of dilute urine. Normal, isotonic (0.9%), and half-isotonic (0.45%) saline (infusion rate of 1 mL/kg per hour for 24 hours, starting at 8 am on the day of the procedure) have been prospectively compared in 1620 patients undergoing coronary angioplasty.13 This study showed a significantly lower incidence of CIN in the group randomized to receive normal saline (0.7% vs. 2.0%, P = 0.04). So far no controlled prospective trial has addressed the value of hydration alone, most probably for ethical reasons.2
All water-soluble CM are excreted mainly by glomerular filtration. CM induce a transient osmotic overload in the ultrafiltrate. This is also the case with isoosmolar CM such as iodixanol. In patients with chronic renal insufficiency, the clearance of CM is slower than in normal subjects with a prolongation of the elimination half-life (normally 70% of the dose is recovered in urine 6 hours after the intravenous injection).14
Besides hydration, other methods are classically recommended to reduce CIN in patients at risk: minimization of the dose injected (eg, avoidance of routine ventriculograms in patients undergoing cardiac catheterization), delaying of subsequent CM-requiring interventions, discontinuation of potentially nephrotoxic treatments where possible, and the use of a low-osmolar CM.1,2 Radiology and cardiology procedures are, in most cases, scheduled beforehand and thus lend themselves rather well to pharmacological prophylaxis.
A study addressed the value of N-acetylcysteine, a compound that, among other properties, is a potent antioxidant, in the prevention of CIN.15 This article, published in the New England Journal of Medicine, created a noteworthy stir in the radiology and cardiology communities, which prompted us to review the prevention of CIN from a pharmacological point of view. Although there are numerous reviews of the literature that include sections dealing with the pharmacological prevention of CIN, to the best of our knowledge, there are no such reviews exclusively and exhaustively discussing the relevant clinical material and examining their pharmacological background and justification.
Knowledge of the pharmacological properties of the drugs used for prophylaxis should allow the clinicians to better understand (1) why there is such variability among the published data, (2) the mechanisms of the reported side effects, and (3) the scientific justification of such trials. In addition, knowledge of the methodological design of the published clinical studies should allow the clinicians to critically evaluate their relevance for their daily practice. Numerous prophylactic approaches, based on putative pathophysiological mechanisms of CIN (Fig. 1), have been tested so far. The present article will review and discuss the principal agents used to prevent such side effects of CM.