Ameliorating Contrast-Induced Nephropathy

As the trend continues towards catheter-based management of cardiovascular disorders, increasing numbers of patients are at risk of developing contrast-induced nephropathy. Development of nephropathy impacts hospital stay, medical care costs, morbidity and mortality. In survivors of contrast-induced nephropathy, renal function may fail to return to normal levels in nearly 30% and long-term implications of this is still unknown.1,2 Contrast-induced nephropathy is believed to be the consequence of contrast-induced vasoconstriction and of renal medullary ischemia resulting from a direct toxic effect of contrast on the renal tubular cells in the outer medullary thick ascending limb.3 Numerous treatments have been tested for their ability to mitigate renal failure following the administration of radiographic contrast. Clinical trials with manitol, diuretics, adenosine anatonists, calcium channel antagonists, dopamine, atrial natriuretic peptides and endothelin receptor antagonists have been disappointing. The use of a non-selective adenosine competitive inhibitor, aminophylline, to prevent contrast-induced nephropathy is reported by Shammas et al. in this issue of the Journal.4 Since the retrospective nature of the investigation is in a small number of patients, it is difficult to draw conclusions with regards to the effect of aminophylline on preventing radiocontrast nephropathy. Thus far, only hydration strategies have been validated in the setting of coronary angiography.5 Tepel et al. demonstrated clinical benefit in a relatively small study of the thiol-containing antioxidant, acetylcysteine, administered orally for 24 hours before and after CT scanning.6 If a similar level of benefit with acetylcysteine can be proven in cardiac patients, then the benefits are likely to be even greater, as the average volume of radiocontrast is higher then the 75 ml of nonionic low-osmolality radiographic contrast agent used. The applicability of 24 hour pretreatment with the antioxidant acetylcysteine is not always possible. Therefore, we are currently evaluating the efficacy and safety of intravenous acetylcysteine and hydration immediately prior to coronary catheterization. Other pharmacological prophylactic strategies such as fenoldopam, a selective dopamine adrenergic (type 1) agonist, are currently being evaluated.7 Unlike the previously tested renal vasodilators (atrial natriutic peptides and low-dose dopamine), which increased renal cortical perfusion, fenoldopam increases blood flow to the renal cortex and medulla; so, it better attenuates renal medullary ischemia. Under normal conditions, the partial pressure of oxygen in the renal medulla is in the range of 10–20 mmHg (cf partial pressure oxygen in renal cortex ~ 50 mmHg). Renal hypoperfusion will exacerbate the hypoxia and lead to medullary tubular cell injury and nephron death. According to Poiseuille’s equation, an increase in blood viscosity will lead to reduce renal blood flow. The viscosity of contrast media is dramatically greater than of blood plasma. Consequently, studies are currently being proposed to evaluate the renal effects of radiocontrast with varying viscosities. Gadolinium, a contrast agent currently used routinely for magnetic resonance imaging, shows no nephrotoxicity at recommended doses (0.3 mmol/kg). However, due to the relatively low maximum dose, satisfactory angiographic definition poses a challenge.8 It seems likely that developments in the near future will be small and incremental, and that iodine contrast-induced nephropathy will be with us for some time.

1. Soloman R. Contrast medium induced acute renal failure. Kidney Int 1998;53:230–242. 2. McCullough P. Acute renal failure after coronary interventions: Incidence, risk factors and relationship to mortality. Am J Med 1997;103:368–375. 3. Porter G. Contrast associated nephropathy: Presentation, pathophysiology and management. Miner Electrolyte Metab 1994;20:232–243. 4. Shammas N. Aminophylline does not protect against radiocontrast nephropathy in patients undergoing percutaneous angiographic procedures. J Invas Cardiol 2001;13:738–740. 5. Stevens M. A prospective randomized trial of prevention measures for contrast nephropathy. Results of the PRINCE study. J Am Coll Cardiol 1999;33:403–411. 6. Tepel M. Prevention of radiographic contrast agent induced reduction in renal function by acetylcystiene. N Engl J Med 2000;343:180–184. 7. Hunter D. Fenoldopam: A dopamine type 1 receptor agonist in the prevention of renal injury associated with the administration of intravascular contrast. J Vasc Intervent Radiol 2000;11:396–398. 8. Sarkis A. Gadolinium based coronary angiography in a patient with renal failure. The first clinical report. Cathet Cardiovasc Intervent 2001;54:68–69.