Radiocontrast Nephropathy Jason S. Finkelstein, M.D. Tulane University HSC Division of Cardiology 3/2/04

Outline Incidence and Clinical Features of RCN Incidence and Clinical Features of RCN Risk Factors Risk Factors Pathophysiology Pathophysiology Agents used for Prevention of RCN Agents used for Prevention of RCN

Incidence In the year 2000, an estimated 1.8 million caths were performed in the US In the year 2000, an estimated 1.8 million caths were performed in the US Two studies looked at 1826/1196 patients and the incidence of RCN was 14.4% & 11.1% respectively Two studies looked at 1826/1196 patients and the incidence of RCN was 14.4% & 11.1% respectively 0.3-4% of patients required short-term dialysis 0.3-4% of patients required short-term dialysis Approx 60,000 cases of RCN occur each year Approx 60,000 cases of RCN occur each year

Definition Absolute increase of Cr > 0.5 mg/dl or relative increase of 25-50% from baseline within 48 hours of contrast exposure in absence of other causes Absolute increase of Cr > 0.5 mg/dl or relative increase of 25-50% from baseline within 48 hours of contrast exposure in absence of other causes Third most common cause of acute renal failure Third most common cause of acute renal failure

Definition Typically occurs within hours of contrast exposure Typically occurs within hours of contrast exposure Creatinine typically peaks in 3-5 days and returns to baseline in 1-3 weeks Creatinine typically peaks in 3-5 days and returns to baseline in 1-3 weeks RCN is non-oliguric in most patients RCN is non-oliguric in most patients

Outcome Causes increased length of hospital stay and costs Causes increased length of hospital stay and costs Significant in-hospital morbidity Significant in-hospital morbidity 5-10% require transient dialysis; <1% require long term dialysis 5-10% require transient dialysis; <1% require long term dialysis

Increased mortality 3.8% -- Increase in Cr mg/dl 3.8% -- Increase in Cr mg/dl 64% -- Increase in Cr > 3.0 mg/dl 64% -- Increase in Cr > 3.0 mg/dl

Osmolality Contrast media are water soluble structures composed of triiodobenzene ring with varying numbers of iodine molecules Contrast media are water soluble structures composed of triiodobenzene ring with varying numbers of iodine molecules Increased iodine content results in increased osmolality Increased iodine content results in increased osmolality Pooled data from 25 randomized trials have shown that high osmolality agents pose a greater risk of CN than low-osmolality agents Pooled data from 25 randomized trials have shown that high osmolality agents pose a greater risk of CN than low-osmolality agents

Risk Factors for RCN Pre-existing renal insufficiency (37%) Pre-existing renal insufficiency (37%) Diabetes (risk is 4.1%) Diabetes (risk is 4.1%) Contrast volume Contrast volume Dehydration Dehydration Advanced Age Advanced Age Nephrotoxic drugs (ACE, NSAIDS) Nephrotoxic drugs (ACE, NSAIDS) CHF, Liver disease CHF, Liver disease

Pathophysiology Medullary ischemia Medullary ischemia Direct tubular toxicity Direct tubular toxicity Tubular obstruction Tubular obstruction

Medullary Ischemia Contrast agents cause a selective renal medullary vasoconstriction Contrast agents cause a selective renal medullary vasoconstriction Shunting of blood to the renal cortex Shunting of blood to the renal cortex Also known as the “steal phenomenon” Also known as the “steal phenomenon” This leads to tubular injury This leads to tubular injury

Tubular obstruction Possible role in pathogenesis of RCN Possible role in pathogenesis of RCN Precipitation of Dye crystals in the renal tubules Precipitation of Dye crystals in the renal tubules In presence of dehydration, precipitation of urate or dye crystals could lead to tubular obstruction In presence of dehydration, precipitation of urate or dye crystals could lead to tubular obstruction

Direct Tubular Toxicity Toxic ATN Toxic ATN Oxygen Free Radicals Oxygen Free Radicals –Leads to apoptosis in renal tubular and glomerular cells

Iohexol Cooperative Study Objective Objective –To compare the incidence of contrast nephrotoxicity between nonionic “Iohexol” and the ionic contrast agent “diatrizoate” in a large population of low and high risk patients undergoing angiogram –1196 pts, randomized trial

Conclusion The incidence of RCN depends on the presence of risk factors The incidence of RCN depends on the presence of risk factors Pts with CRI and DM are at highest risk Pts with CRI and DM are at highest risk RCN can be associated with significant morbidity and mortality RCN can be associated with significant morbidity and mortality There are preventive interventions to decrease the risk of toxicity There are preventive interventions to decrease the risk of toxicity