Acute kidney injury (AKI), including contrast-induced nephropathy (CIN), is associated with long-term adverse event rates, particularly cardiovascular events. An important question is whether the AKI is a cause of these long-term adverse events or just a ├óÔé¼´åİmarker™ of the burden of cardiovascular risk factors. The Cardiac Angiography in Renally Impaired Patients (CARE) and CARE follow-up trials provide insight into the answer to this vital question. In the CARE follow-up trial the incidence of CIN was reduced in one arm of the study. Despite similar risk factor burden at baseline, the patient group with a lower incidence of CIN experienced significantly fewer adverse cardiovascular events at one year. In this article, the relationship between CIN and long-term adverse events is explored and the pathogenic mechanism linking these two temporally distant events is explored.
Acute kidney injury (AKI), contrast-induced nephropathy, outcomes, angiography
Disclosure: Richard Solomon, MD, FASN, has consulting agreements with Bracco Diagnostics Inc. and Covidien.
Received: November 4, 2009 Accepted: December 21, 2009
Citation: US Cardiology, 2010;7(1):42├óÔé¼ÔÇ£6 Correspondence: Richard Solomon, MD, FASN, UHC 2309, 1 South Prospect St, Burlington, VT 05401. E: Richard.Solomon@vtmednet.org
Acute kidney injury (AKI) is a frequent occurrence in hospitalized patients and its overall incidence appears to be increasing. In addition, the number of patients in whom AKI is preceded by exposure to iodinated contrast is also increasing (see Figure 1). Patients who develop AKI in hospital are typically those undergoing major surgical procedures and individuals suffering from hemodynamic insults, such as gastrointestinal bleeding, myocardial infarction, or sepsis. AKI also occurs in outpatients, where the etiology is more likely to be caused by nephrotoxins such as contrast media administered during coronary angiography and contrast-enhanced CT exams. For both inpatients and outpatients with AKI, regardless of etiology, there is a strong association between the occurrence of AKI and adverse events.1 These adverse events include increased length of hospital stay, greater hospital costs and in-hospital mortality, increased cardiovascular events, progression to end-stage kidney disease, and increased mortality at one year.
The association between AKI and adverse outcomes has been found across diverse cohorts of patients and etiologies of AKI.1 Despite this consistent association, it remains unclear whether the kidney injury itself is the cause of the subsequent adverse events. This is particularly relevant when discussing the relationship between AKI and events that occur months to years after the episode that produced the AKI. It could be argued that there is something about the patients who develop AKI that predisposes them to these longterm adverse events. For example, patients who have a significant burden of cardiovascular risk factors (e.g. those with diabetes and hypertension) are more likely to suffer AKI following a hemodynamic insult and independently to have a higher risk for long-term cardiovascular events such as stroke or myocardial infarction, and even death. In such patients, AKI may be a ├óÔé¼´åİmarker™ of cardiovascular risk factor burden. Alternatively, AKI may in some direct way accelerate the atherosclerotic process, increasing the likelihood of a future stroke, acute myocardial infarction, or death. In these patients, AKI may be a cause of the later adverse events. Distinguishing between these two possibilities is not easy. However, the impact of these two possible explanations is vastly different.
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- Coca S, Bushra Y, Shlipak MG, et al., Long-term risk of mortality and other adverse outcomes after acute kidney injury: a systemic review and meta-analysis, Am J Kidney Dis, 2008;53:961├óÔé¼ÔÇ£73.
- Solomon R, Natarajan MK, Doucet S, et al., The CARE (Cardiac Angiography in REnally Impaired Patients) Study: A randomized, double-blind trial of contrast-induced nephropathy in high risk patients, Circulation, 2007;115: 3189├óÔé¼ÔÇ£96.
- Solomon R, Mehran R, Natarajan MK, et al.,Contrast-induced nephropathy and long-term adverse events: cause and effect?, Clin J Am Soc Nephrol, 2009;4:1162├óÔé¼ÔÇ£9.
- Dharnidharka VR, Kwon C, Stevens G, Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis, Am J Kid Dis, 2002;40:221├óÔé¼ÔÇ£5.
- Sjostrom P, Tidman M, Jones I, The shorter T1/2 of cystatin C explains the earlier change of its serum level compared to serum creatinine, Clin Nephrol, 2004;62:241├óÔé¼ÔÇ£2.
- Mehta RL, Kellum JA, Shah SV, et al., Acute kidney injury network (AKIN): report of an initiative to improve outcomes in acute kidney injury, Crit Care, 2007;11:R31.
- Brenner B, Lawler EV, Mackenzie HS, The hyperfiltration theory: a paradigm shift in nephrology, Kidney Int, 1996;49: 1774├óÔé¼ÔÇ£7.
- McCullough P, Jurkovitz CT, Pergola PE, et al., for the KEEP Investigators. Independent components of chronic kidney disease as a cardiovascular risk state, Arch Intern Med, 2007;167:1122├óÔé¼ÔÇ£9.
- Lo L, Go AS, Chertow GM, et al., Dialysis-requiring acute renal failure increases the risk of progressive chronic kidney disease, Kidney Int, 2009;76:893├óÔé¼ÔÇ£9.
- Amdur R, Chawla LS, Amodea S, et al., Outcomes following diagnosis of acute renal failure in U.S. veterans: focus on acute tublular necrosis, Kidney Int, 2009;76:1087├óÔé¼ÔÇ£97.
- Ishani A, Xue JL, Himmelfarb J, et al., Acute kidney injury increases risk of ESRD among elderly, J Am Soc Nephrol, 2009;20:223├óÔé¼ÔÇ£8.
- Mehran R, Aymong ED, Nikolsky E, et al., A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: development and initial validation, J Am Coll Cardiol, 2004;44:1393├óÔé¼ÔÇ£9.
- Goldenberg I, Chonchol M, Guetta V, Reversible acute kidney injury following contrast exposure and the risk of long-term mortality, Am J Nephrol, 2009;29:136├óÔé¼ÔÇ£44.
- Masuda M, Yamada T, Okuyama Y, et al., Sodium bicarbonate improves long-term clinical outcomes compared to sodium chloride in patients with chronic kidney disease undergoing an emergent coronary procedure, Circ J, 2008;72:1610├óÔé¼ÔÇ£14.