Contrast Media, Cardiovascular Interventions and Kidney Injury – Does Contrast Osmolarity Matter?
• vasoconstriction; • direct and indirect renal cell toxicity; and • tubular obstruction.
All of these adverse events may cumulate in renal medulla ischaemia.4
Extrinsic factors that can potentiate these deleterious intrarenal effects include dehydration and impaired cardiac output.5
Direct cellular injury
Hyperosmolar contrast media have been associated with induction of vasoconstriction after intravascular delivery.6
It is suggested that
this is due in part to increased levels of reactive oxygen species7 and an impairment of endothelial function, possibly mediated by the impairment of endothelium-derived nitric oxide availability and function.8
Recently, a study has compared the effects of iso-
osmolar and higher-osmolar contrast media on renal blood flow. In this small study, iso-osmolar contrast media had no effect on the renal resistance index, whereas hyperosmolar contrast media impaired renal blood flow.9
Contrast media may also induce direct
cytotoxic effects by induction of renal cell apoptosis, as recently shown by Romano and co-workers.10
In this pre-clinical study, no
differences between iso-osmolar and higher-osmolar contrast media could be detected.
Although the risk of CIN is negligible in patients presenting with normal renal function, it can reach double-digit percentage levels in patients with advanced CKD.11
Besides impaired renal function, other
risk factors such as diabetes, concomitant nephrotoxic medication, volume of contrast medium delivered, hypotension, cardiogenic shock or congestive heart failure may aggravate the risk of CIN in renal patients.12
Development of CIN is associated with adverse outcomes.13 This is
particularly the case for patients who require transient or permanent dialysis subsequent to contrast exposure. In these patients, subsequent one-year mortality can be up to 30% or higher.14,15
Even small and temporary reductions in renal function
are considered to impose a negative long-term effect subsequent to cardio-angiography.16
The fear of CIN is probably the most
important reason patients with CKD are less likely to undergo PCI compared with patients with normal kidney function, even though they are at increased risk of a major cardiac event if they are not appropriately revascularised. This paradox was recently documented in the large European GRACE registry.3
Physicians
have to use safe contrast media and carefully follow guidelines to lessen the risk of CIN by, for example, proper hydration before and after the procedure, as well as keeping the amount of contrast to a minimum.
Cardiorenal Syndrome
It has become evident that a significant subset of patients have different grades of both cardiac and renal dysfunction,17
since a
primary disorder of one of these organs often results in a secondary dysfunction of the other.18
Moreover, both organs can be
simultaneously injured by a systemic condition such as diabetes or sepsis. The interaction between dysfunction of the heart and kidney therefore provides the pathophysiological basis for cardiorenal syndrome.19
This syndrome is currently categorised into five subtypes
depending on the primary affected organ, occurrence of symptoms (acute versus chronic) or presence of a primary systemic disease that simultaneously adversely affects both tissues.19
EUROPEAN NEPHROLOGY
The findings of the COURT trial were confirmed by the VICC study, which included 1,276 patients. Use of iodixanol was associated with a highly significant reduction in in-hospital MACE compared with iopamidole (4.8 versus 9.0%; p=0.003). Unfortunately, the results of this study are only available in abstract form and were never published in a peer-reviewed journal.21
Recently, the CONTRAST study, which comprised patients undergoing PCI, showed a similar trend towards a lower MACE rate at six months in favour of iso-osmolar contrast media, although this study was not powered for clinical end-points.11
The precise reason for these
findings is unclear; however, in vitro data have suggested that the degree of contrast media osmolarity may be the most important factor in its interaction with platelet activation and degranulation.22 Other in vitro studies have suggested that hyperosmolar contrast media cause greater endothelial dysfunction than iso-osmolar non- ionic contrast media.23
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Major Adverse Cardiovascular Event Rate and Use of Iso- and Hyperosmolar Contrast Media
Contrast osmolarity may be associated with the rate of major adverse cardiovascular events (MACE). One of the largest studies, comprising 856 patients, that investigated the effect of iso-osmolar versus higher- osmolar contrast media on MACE rate was the COURT study. This study used contemporary PCI techniques, such as glycoprotein IIb/IIIa inhibitors and stents.20
It reported a 45% reduction of in-hospital
MACE in favour of iso-osmolar iodixanol compared with hyper- osmolar ioxaglate (5.4 and 9.5%, respectively; p=0.027).
Cardiorenal syndrome also emphasises the important clinical fact that the long-term outcome of cardiovascular interventions is not solely determined by the immediate interventional result. Long-term outcome is positively affected by avoiding acute renal complications, in particular the prevention of CIN.
Contrast-induced nephropathy
This fairly novel clinical entity might be helpful for the appreciation of the effects of contrast media that can adversely affect both cardiac and renal tissues, the latter being termed CIN.
Tubular obstruction Vasoconstriction
Figure1: Schematic Illustration of Major Causes of Contrast-induced Nephropathy
Endothelin Adenosine
Reactive oxygen species
Prostaglandins
Endothelium-derived nitric oxide
Tubular injury
Renal tissue ischaemia
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