Background: Contrast-induced acute kidney injury (AKI) is a significant cause of morbidity and mortality among hospitalized patients. However, data regarding the long-term prognostic implications of reversible AKI following contrast exposure are limited. Methods: We carried out a prospective 5-year follow-up study of 78 patients with chronic kidney disease who underwent coronary angiography, employing a uniform intravenous hydration protocol supplemented by either acetylcysteine (600 mg orally t.i.d.) or placebo. Results: Contrast-induced AKI (defined as ≥0.5 mg/dl increase in serum creatinine, SCr, or >25% increase above baseline 48 h following contrast exposure) developed in 10 of the 78 patients (13%). All SCr changes were reversible, and were no longer evident 7 days following contrast exposure. At 5 years of follow-up, mortality rates were significantly higher among patients who developed reversible AKI (90%) as compared with those who did not (32%; p < 0.001). Accordingly, multivariable analysis demonstrated that reversible AKI was independently associated with a significant 2.7-fold increase (p = 0.001) in the risk of long-term mortality. Conclusions: Our findings indicate that short-term reductions in renal function following contrast exposure have important long-term prognostic implications in patients with chronic kidney disease. Careful follow-up of SCr levels following contrast exposure is warranted for long-term risk assessment in this population.

Keywords:
Contrast-induced acute kidney injury, Chronic kidney disease, Contrast media
1.
Levy EM, Viscoli CM, Horwitz RI: The effect of acute renal failure on mortality. A cohort analysis. JAMA 1996;275:1489–1494.
2.
Best PJ, Lennon R, Ting HH, Bell MR, Rihal CS, Holmes DR, Berger PB: The impact of renal insufficiency on clinical outcomes in patients undergoing percutaneous coronary interventions. J Am Coll Cardiol 2002;39:1113–1119.
3.
Rich MW, Crecelius CA: Incidence, risk factors and clinical course of acute renal insufficiency after cardiac catheterization in patients 70 years of age or older: a prospective study. Arch Intern Med 1990;150:1237–1242.
4.
Mangano CM, Diamondstone LS, Ramsay JG, Aggarwal A, Herskowitz A, Mangano DT: The Multicenter Study of Perioperative Ischemia Research Group. Renal dysfunction after myocardial revascularization: risk factors adverse outcomes, and hospital resource utilization. Ann Intern Med 1998;128:194–203.
5.
Rihal CS, Textor SC, Grill DE, Berger PB, Ting HH, Best PJ: Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention. Circulation 2002;105:2259–2264.
6.
McCullough PA, Wolyn R, Rocher LL, Levin RN, O’Neill WW: Acute renal failure after coronary intervention: incidence, risk factors, and relationship to mortality. Am J Med 1997;103:368–375.
7.
Barrett BJ: Contrast nephrotoxicity. J Am Soc Nephrol 1994;5:125–137.
8.
Solomon R, Werner C, Mann D, D’Elia J, Silva P: Effects of saline, mannitol, and furosemide on acute decreases in renal function induced by radiocontrast agents. N Engl J Med 1994;331:1416–1420.
9.
Barrett BJ, Parfrey PS: Prevention of nephrotoxicity induced by radiocontrast agents. N Engl J Med 1994;331:1449–1450.
10.
Tepel M, van der Giet M, Schwarzfeld C, Laufer U, Liermann D, Zidek W: Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine. N Engl J Med 2000;343:180–184.
11.
Diaz-Sandoval LJ, Kosowsky BD, Losordo DW: Acetylcysteine to prevent angiography-related renal tissue injury (the APART trial). Am J Cardiol 2002;89:356–358.
12.
Briguori C, Manganelli F, Scarpato P, Elia PP, Golia B, Riviezzo G, Lepore S, Librera M, Villari B, Colombo A, Ricciardelli B: Acetylcysteine and contrast agent-associated nephrotoxicity. J Am Coll Cardiol 2002;40:298–303.
13.
Shyu KJ, Cheng JJ, Kuan P: Acetylcysteine protects against acute renal damage in patients with abnormal renal function undergoing a coronary procedure. J Am Coll Cardiol 2002;40:1383–1388.
14.
Marenzi G, Assanelli E, Marana I, Lauri G, Campodonico J, Grazi M, De Metrio M, Galli S, Fabbiocchi F, Montorsi P, Veglia F, Bartorelli AL: N-acetylcysteine and contrast-induced nephropathy in primary angioplasty. N Engl J Med 2006;354:2773–2782.
15.
Goldenberg I, Shechter M, Matetzky S, Jonas M, Adam M, Pres H, Elian D, Agranat O, Schwammenthal E, Guetta V: Oral acetylcysteine as an adjunct to saline hydration for the prevention of contrast-induced nephropathy following coronary angiography. A randomized controlled trial and review of the current literature. Eur Heart J 2004;25:212–218.
16.
Levey AS, Bosch JP, Lewis JB, Greene T, Rodgers N, Roth D: A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med 1999;130:461–470.
17.
National Kidney Foundation: Kidney Disease: Outcome Quality Initiative (K/DOQI) clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney 2002;39(suppl 1):S1–S266.
18.
Gruberg L, Mintz GS, Mehran R, Gangas G, Lansky AJ, Kent KM, Pichard AD, Satler LF, Leon MB: The prognostic implications of further renal function deterioration within 48 h of interventional coronary procedures in patients with pre-existent chronic renal insufficiency. J Am Coll Cardiol 2000;36:1542–1548.
19.
Mueller C, Buerkle G, Buettner HJ, Petersen J, Perruchoud AP, Eriksson U, Marsch S, Roskamm H: Prevention of contrast media-associated nephropathy: randomized comparison of 2 hydration regimens in 1620 patients undergoing coronary angioplasty. Arch Intern Med 2002;162:329–336.
20.
Merten GJ, Burgess WP, Gray LV, Holleman JH, Roush TS, Kowalchuk GJ, Bersin RM, Van Moore A, Simonton CA 3rd, Rittase RA, Norton HJ, Kennedy TP: Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial. JAMA 2004;29:2328–2334.
21.
Solomon RJ, Natarajan MK, Doucet S, Sharma SK, Staniloae CS, Katholi RE, Gelormini JL, Labinaz M, Moreyra AE, Investigators of the CARE Study: Cardiac Angiography in Renally Impaired Patients (CARE) study: a randomized double-blind trial of contrast-induced nephropathy in patients with chronic kidney disease. Circulation 2007;115:3189–3196.
22.
Weisberg LS, Kurnik PB, Kurnik BR: Radiocontrast-induced nephropathy in humans: role of renal vasoconstriction. Kidney Int 1992;41:1408–1415.
23.
Battenfeld R, Khater A el-R, Drommer W, Guenzel P, Kaup FJ: Ioxaglate-induced light and electron microscopic alterations in the renal proximal tubular epithelium of rats. Invest Radiol 1991;26:35–39.
24.
Katholi RE, Woods WT Jr, Taylor GJ, Deitrick CL, Womack KA, Katholi CR, McCann WP: Oxygen free radicals and contrast nephropathy. Am J Kidney Dis 1998;32:64–71.
25.
Drager LF, Andrade L, Barros de Toledo JF, Laurindo FR, Machado César LA, Seguro AC: Renal effects of N-acetylcysteine in patients at risk for contrast nephropathy: decrease in oxidant stress-mediated renal tubular injury. Nephrol Dial Transplant 2004;19:1803–1807.
26.
Safirstein R, Andrade L, Vieira JM: Acetylcysteine and nephrotoxic effects of radiographic contrast agents: a new use for an old drug. N Engl J Med 2000;343:210–212.
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2008
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