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Nefropatia Induzida Por Contraste NEJM2019
Nefropatia Induzida Por Contraste NEJM2019
Review Article
C
From the Zena and Michael A. Wiener ontrast-associated acute kidney injury is characterized by a
Cardiovascular Institute, Icahn School decrease in kidney function that occurs within days after the intravascular
of Medicine at Mount Sinai, New York
(R.M., G.D.D.); and the Veterans Affairs administration of iodinated contrast material. In the 1950s, initial cases
Pittsburgh Healthcare System and Uni- were reported in patients with preexisting kidney disease who were undergoing
versity of Pittsburgh School of Medicine, intravenous pyelography with contrast agents that were associated with a high
Pittsburgh (S.D.W.). Address reprint re-
quests to Dr. Mehran at the Zena and incidence of acute kidney injury and other adverse effects.1-4 Over time, an evolu-
Michael A. Wiener Cardiovascular Institute, tion in the design of contrast agents, improved recognition of risk factors, and
Icahn School of Medicine at Mount Sinai, implementation of preventive care resulted in lower rates of acute kidney injury
1 Gustave L. Levy Pl., New York, NY 10029,
or at roxana.mehran@mountsinai.org. after the administration of contrast material5-7 (Fig. 1). More recent studies have
suggested that the risk of acute kidney injury due to contrast material is overesti-
N Engl J Med 2019;380:2146-55.
DOI: 10.1056/NEJMra1805256 mated.9-13 Such studies are important, considering that angiographic procedures
Copyright © 2019 Massachusetts Medical Society. may be underused in patients with chronic kidney disease who present with condi-
tions such as acute coronary syndromes, presumably because of concern about
precipitating acute kidney injury.14 This review summarizes the pathophysiology of
contrast-associated acute kidney injury, the diagnostic criteria, and risk stratifica-
tion; discusses current controversies regarding the incidence of this condition; and
highlights studies that have provided the evidence that forms the basis for preven-
tive care.
Iodine
Concentration 370 320 200–370 270–320
(mg/ml)
Osmolality
(mOsm/kg H2O) 1551 ~600 413–796 290
Viscosity
10.5 7.5 2.0–9.4 6.3–11.8
(mPa.sec at 37°C)
that has increased by at least 0.3 mg per deciliter factor for contrast-associated acute kidney injury.24
(26.5 μmol per liter) over the baseline value Although diabetes mellitus is commonly cited as
within 48 hours after exposure to contrast me- a risk factor, data from the Iohexol Cooperative
dium, or a urinary volume of less than 0.5 ml Study, performed more than 20 years ago, showed
per kilogram of body weight per hour that per- that it was not an independent risk factor but
sists for at least 6 hours after exposure.22 Al- rather amplified susceptibility in patients with
though the plasma creatinine component of this underlying chronic kidney disease.25 As compared
definition has reasonable sensitivity, its specific- with the early, high-osmolality contrast agents,
ity is poor, because plasma creatinine levels low-osmolality and iso-osmolality agents are as-
fluctuate owing to fluid shifts and medication sociated with a lower risk of kidney injury and
effects. Since other factors (e.g., medications, their use is recommended (class I recommenda-
hypotension, or atheroemboli) can precipitate tion, level of evidence A) by the European Society
acute kidney injury after exposure to contrast of Cardiology and the American Heart Associa-
medium, the term “contrast-associated acute tion–American College of Cardiology.25-28 Use
kidney injury” has gained favor. of contrast medium at a high volume (>350 ml
The risk of acute kidney injury after the ad- or >4 ml per kilogram) or repeated administra-
ministration of contrast material is also influ- tion within 72 hours after initial administration
enced by patient- and procedure-related factors. has been shown to be associated with an in-
Preexisting chronic kidney disease is the stron- creased risk.18,29
gest patient-related risk factor, with lower levels There is also evidence that the risk of acute
of kidney function associated with higher degrees kidney injury varies with the clinical presentation
of risk.23 An analysis of data from 985,737 pa- and the type of imaging procedure. For example,
tients undergoing percutaneous coronary inter- patients with ST-segment elevation myocardial
vention (PCI) confirmed that severe chronic kid- infarction who undergo PCI have a particularly
ney disease was the strongest independent risk high risk of contrast-associated kidney injury.30
D IR EC T IN D IR E C T
Na+/K+-ATPase Proximal
Lumen tubule
Nephrotoxic Disturbances in
effects renal blood flow
Na+
Tubular Tubular
obstruction injury
Apoptosis
It is generally believed that arteriography is associ- of contrast-associated acute kidney injury and
ated with a higher risk than computed tomogra- spurred research to identify preventive strategies.
phy (CT), owing to delivery of more concentrated However, the reports are solely associational
contrast material to the kidneys with arteriograph- (Fig. S1 in the Supplementary Appendix). It is
ic procedures and the higher overall risk profile plausible that contrast-associated acute kidney
of patients requiring such procedures. injury is a marker of an increased risk of serious
A series of risk-stratification models that in- adverse outcomes rather than a mediator of such
corporate patient and procedural factors have outcomes. Support for such a view derives from
been validated in past studies (Table S1 in the a study by Lassnigg et al.,43 who found that al-
Supplementary Appendix, available with the full though small postsurgical elevations in plasma
text of this article at NEJM.org).18,31-34 A strength creatinine levels were associated with increased
of these risk-stratification models is that they 30-day mortality, small decrements in plasma
are derived from data based on large numbers of creatinine levels (≤0.5 mg per deciliter) were also
patients. However, there are caveats to their associated with increased mortality (hazard ratio,
clinical use — namely, the inclusion of variables 2.27; 95% CI, 1.28 to 4.03). Such fluctuations (up
(e.g., the volume of contrast material adminis- or down) in plasma creatinine levels after surgical
tered and use or nonuse of a hemodynamic- or radiographic procedures are probably due to
support device) that are unknown before the hemodynamic instability, decreased renovascular
procedure. Furthermore, most of these models autoregulation, or both, rather than an actual
were developed in studies involving patients cause of adverse downstream events. A meta-
undergoing PCI, which limits their generaliz- analysis by Coca et al. showed that interventions
ability. that reduced the incidence of acute kidney injury
by nearly 50% failed to reduce the risk of longer-
term death (relative risk, 0.97; 95% CI, 0.82 to
Ser ious A dv er se Ou t c ome s
a nd Impl ic at ions for Cl inic a l 1.16) or the development of chronic kidney dis-
Pr ac t ice ease (relative risk, 0.87; 95% CI, 0.52 to 1.46).44
These observations raise doubt about causation
Many studies have shown that contrast-associated between small increments in plasma creatinine
acute kidney injury, defined by small decrements levels after the administration of contrast ma-
in kidney function, is associated with increased terial and adverse downstream events; they also
mortality.31,35-41 Contrast-associated acute kidney underscore the problem in defining contrast-
injury is also correlated with accelerated pro- associated acute kidney injury on the basis of
gression of underlying chronic kidney disease. small increments in a biologic marker (i.e., plasma
James et al. reported that the risk of a sustained creatinine) that are neither specific for injury
reduction in kidney function at 90 days was due to the administration of contrast material
greater for patients who had acute kidney injury nor definitively indicative of intrinsic kidney
after undergoing coronary angiography than for damage. To date, there have been no adequately
those who did not have acute kidney injury.42 For powered clinical trials showing that prevention
patients with mild acute kidney injury, the ad- of contrast-associated acute kidney injury results
justed odds ratio was 4.7 (95% confidence inter- in a survival benefit.
val [CI], 3.9 to 5.7), and for those with more Whether contrast-associated acute kidney in-
severe acute kidney injury, the adjusted odds ratio jury represents a mediator or a marker of adverse
was 17.3 (95% CI, 12.0 to 24.9), supporting a outcomes, it appears likely that the many studies
graded relationship between the severity of acute documenting these associations have had impor-
kidney injury and the risk of sustained kidney tant unintended consequences for clinical care.
impairment. Accordingly, deteriorating kidney A large and growing number of studies have
function after angiography or angioplasty has shown that patients with chronic kidney disease
been characterized as a major procedural com- are less likely to undergo coronary angiography
plication in the National Cardiovascular Data and revascularization than patients who do not
Registry.24 have chronic kidney disease.14,45-57 It has been
Collectively, these studies and others with hypothesized that concern about the risk of con-
similar findings undoubtedly raised awareness trast-associated acute kidney injury explains these
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