Contrast-Induced Nephropathy and Cardiac Catheterization: Evidence in Support of Using the Iso-Osmolar Contrast Agent Iodixano

Leonard Ilkhanoff, MD* and Joseph Carver, MD†
Leonard Ilkhanoff, MD* and Joseph Carver, MD†
Unlike patients with well-preserved renal function, in whom the choice of radio contrast agent appears to have minimal impact on the development of contrast-induced nephropathy (CIN), the patient with chronic kidney disease (CKD) historically has presented numerous challenges to the cardiologist performing cardiac catheterization. Studies have suggested that CKD not only increases cost and prolongs hospitalization, but also confers an increase in major adverse cardiovascular event (MACE) rates in patients undergoing cardiac catheterization for both the index hospitalization and long-term, especially in the subset of patients undergoing percutaneous coronary intervention (PCI).1 Therapies Aimed at Mitigating CIN Numerous therapies that may mitigate the development of CIN have been studied. The use of fenoldopam,2 atrial natriuretic peptide,3 and theophylline4 have shown no benefit and are currently not used in routine practice. In contrast, administration of peri-procedural intravenous fluids5 and use of N-acetylcysteine (NAC)6,7 have shown benefit, and are used more commonly as potential safeguards for CIN, especially in patients with baseline renal dysfunction and diabetes.7 Focus on Contrast Agents In addition to hydration and NAC, limiting the amount of contrast given to a patient with CKD has been the historical standard of care for angiography. The type of contrast agent used (low-osmolar versus iso-osmolar) for cardiac catheterization has only recently gained increased attention. Although low-osmolar agents are commonly used in patients with normal renal function, the use of iso-osmolar agents has been suggested to confer renal protection in patients undergoing cardiac catheterization with underlying renal dysfunction or with underlying diabetes mellitus. In this issue of the Journal, Tadros et al.8 present the results of an important study addressing the role of iso-osmolar contrast agents in cardiac catheterization for patients with advanced CKD. This retrospective study investigated the association between volume of iso-osmolar contrast agent used (iodixanol) and the development of CIN (defined as an absolute rise in serum creatinine > 0.5 mg/dL and/or a rise > 25% from baseline creatinine), and the need for dialysis in patients with moderate-to-severe CKD (defined as a creatinine clearance less than 60 ml/min using the Cockroft-Gault equation). In this study, the mean dose of contrast (84.3 ± 67 ml in 117 patients) was not necessarily associated with the development of a higher incidence of CIN, even in those patients who subsequently underwent ad hoc PCI, where higher contrast volumes were used. This finding is in contrast to prior studies that have shown that volume was indeed important and an independent predictor of CIN.9–11 While a prior study12 suggested that iodixanol was less nephrotoxic than iohexol, the more recent study by Aspelin13 is the only randomized, double-blind, prospective, multi-center trial to date examining the use of iodixanol in patients with diabetes and a range of baseline creatinines (1.5 to 3.5 mg/dL) who underwent elective coronary or aortofemoral angiography. Mean volume of contrast administered in this study (163 ml) was similar between the iodixanol and iohexol groups and similar to those patients in the Tadros study undergoing ad hoc PCI. Patients in both groups were also similarly matched in the amount of peri-procedural hydration. The primary endpoint was the peak increase from baseline in the creatinine concentration during the three days after angiography. The creatinine concentration increased significantly less in patients who received iodixanol than in patients who received iohexol. The authors suggest that the development of renal dysfunction was less severe and adverse events were fewer in patients undergoing angiography with iodixanol in a group of patients with a broad range of serum creatinines. The Tadros paper provokes interesting questions as we move forward with better devices and procedural skills and as we attack coronary lesions in a sicker population of patients: 1) Is volume of contrast important? We think that the jury is still out. Less contrast volume was used in the Tadros study compared to prior studies, so the impact of higher amounts of contrast volume on further decrement in renal function still needs to be addressed, especially in combination with hydration and NAC. 2) Is the type of contrast agent important? This too is still undecided, but the current evidence points to a benefit of iso-osmolar contrast, especially in high-risk patients. An ongoing, prospective study (VALOR trial) may provide additional evidence possibly in favor of iodixanol. 3) Who should we worry about? It is clear that we can identify the high-risk patients (acute versus elective procedures; patients within the full range of acute coronary syndromes; older patients; and patients with peri-procedural hypotension and/or shock, diabetes and congestive heart failure) who need the full armamentarium of therapies available in 2005 that may mitigate the development of CIN. Iodixanol may ultimately prove more beneficial than low-osmolar agents in patients with moderate CKD (Cr Cl
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