CIN is the third most common cause of hospital acquired acute renal failure. Recently, important clinical trials on CIN have been completed. Today, there is more agreement on the definition of CIN and a better understanding of which patients are at increased risk of developing CIN. Also, new insights into the pathogenesis of the renal injury are leading to innovative pharmacologic strategies.

Definition and Clinical Implications of CIN
For clinical and research purposes CIN is defined as an acute decline in renal function (rise in serum creatinine by 25% or greater than 0.5mg/dL from baseline or fall in glomerular filtration rate (GFR) by greater than 25%) after systemic contrast administration in the absence of other causes.¹ Typically, CIN onset occurs within 24–48 hours of exposure, serum creatinine levels peak in 3–5 days, and renal function returns to baseline in 7–21 days. If renal function does not return to baseline, other possible causes of renal injury like atheroembolism should be suspected.¹ The incidence of CIN is less than 5% in patients with normal renal function and 15–50% in patients with baseline renal dysfunction (creatinine clearance less than 60mL/min).¹ The incidence of dialysis-dependent acute tubular necrosis is 1.3 to 19%. CIN is an indicator of marked increase in short-term and late mortality. Acute renal failure after coronary intervention is associated with a 36% in-hospital mortality rate and a 19% two-year survival rate.^2-4

Pathogenesis of CIN
The pathogenesis of CIN is complex, with a cascade of contributing factors that are not fully understood.⁵ After injection of contrast media, renal blood flow increases transiently, followed by a more prolonged decrease, particularly at the corticomedullary junction of the kidney. The outer medulla is particularly susceptible to ischemic injury because of its high metabolic activity and low prevailing oxygen tension. Associated with the decrease in renal blood flow there is a decrease in glomerular filtration rate due to afferent renal arteriolar vasoconstriction which is calcium dependent with increased intrarenal adenosine and increased endothelium-1 activity as likely mediators of the vasoconstriction. The risk of CIN increases if there are inadequate compensatory vaso-dilatory responses such as prostaglandins (E2 and I2) and nitric oxide.

Renal tubular cellular injury at least in part is mediated by generation of oxygen-free radicals. Intrarenal adenosine accumulates due to the depletion of adenosine triphosphate as a consequence of proximal tubular stress due to osmotic load and the large size of CM molecules.The renal toxicity from the direct effects of CM is reversible, as has been shown in vitro in studies in which renal tubular cells responded to CM exposure by increasing the concentrations of extracellular adenosine and by decreasing the activity of mitrochondrial enzymes without altering viability.⁶ A late effect of intrarenal adenosine is oxygen free radical production due to the catabolism of intrarenal adenosine to xanthine^.7

A role for intrarenal adenosine as a renal vasoconstrictor and substrate for oxygen-free radical formation is supported in human studies. Adenosine increases in urine following CM; the magnitude of adenosine release and depression of creatinine clearance is proportional to the osmolatity of the contrast agent, essentially a dose response relation.⁸ Further, an inhibitor of adenosine uptake, dipyridamole, exacerbates the fall in GFR after CM.