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Letters to the Editor |
Department of Radiology, Boston University School of Medicine, Atrium 2, 88 East Newton Street, Boston, MA 02118. e-mail: tello@bu.edu
Editor:
It is commendable that work such as that of Dr Huber and colleagues (1) in the June 2002 issue of Radiology is available for the general radiology community to be made aware of. Thus, it is with great interest in this work that this letter is motivated. The ability to validate potential renal protective effects of theophylline by means of blockade of adenosine-cAMP–mediated vasoconstriction is an important area of investigation. Unfortunately, the literature has suffered from prior work (2) in which false-negative results were provided (type II error) because of small sample size. However, the investigation of general protective effects should include not only this reference (2), but also the work of Chan et al (3), in which it was established that reduced cortical flow after lithotripsy demonstrates that aminophylline attenuated this response in the kidneys subjected to lithotripsy. In particular, the underlying mechanism of ischemic change by means of cAMP and the postulate that aminophylline and/or theophylline administration should have a role in protecting the kidneys not only during contrast material administration but also potentially during organ harvesting was put forth in 1996 (4) and should also have been cited.
This is an important area of investigation, and hopefully, further work will enter daily clinical practice, as was the hope when the original stress studies were performed.
REFERENCES
and
Kathrin Ilgmann, *
Departments of Internal Medicine II* and Diagnostic Radiology, Klinikum Rechts der Isar, Technical University of Munich, Ismaningerstrasse 22, D-81675 Munich, Germany. e-mail: wolfgg.huber@t-online.de
In his letter, Dr Tello emphasizes the role of adenosine in the pathophysiology of contrast material–induced nephropathy. We agree that adenosine-mediated afferent arteriolar vasoconstriction is a crucial pathomechanism of renal impairment by contrast agents. Including the two studies of Erley et al (1,2), our pilot study (3), and the trials of Katholi et al (4) and Kolonko et al (5) with a total of 520 patients, there is much evidence for the prophylactic effectiveness of theophylline. We agree with Dr Tello that the studies of Shammas et al (6) and Abizaid et al (7), including 26 and 20 patients undergoing theophylline treatment, respectively, might have been too small to detect the beneficial effects of theophylline (type II error).
Nevertheless, the pathophysiology of contrast material–induced nephropathy is complex. Apart from adenosine, vasoconstriction caused by endothelin and angiotensin converting enzyme, as well as inhibition of vasodilators such as nitric oxide and prostaglandins, contribute to reduced renal perfusion.
Therefore, prostaglandins (8), endothelin antagonists (9), and several other vasodilators have been investigated in the prophylaxis of contrast material–induced nephropathy. However, the results were disappointing. In the study of Koch et al (8), this might result from small sample size (n = 23 to n = 32 in the treatment groups), too. Another explanation might be the systemic vasodilatation induced by prostaglandins and endothelin antagonists. This might result in hypotension with reduced renal perfusion in some of the patients, as mentioned by Koch et al (8) and Wang et al (9). Vasoconstriction induced by adenosine is restricted to the renal microcirculation, since in most other tissues, adenosine leads to vasodilatation. Therefore, a "selective renal inhibitor" of vasoconstriction such as theophylline or—even more specific—selective adenosine-A1-receptor antagonists, might be superior with regard to side effects.
In addition to contrast material–induced renal impairment, an important pathogenetic role of adenosine has been found in other types of toxic or traumatic renal impairment, including extracorporal shockwave lithotripsy. A preventive effect of specific adenosine-A1-receptor antagonists such as KW-3902 has been found in studies on renal impairment induced by aminoglycosides (10), hypoxia (11,12), and lipopolysaccharide (13). Most of these studies were performed in animals by using invasive techniques. With regard to the well-known limitations of these techniques in clinical studies, imaging of renal perfusion with functional magnetic resonance imaging might be an important noninvasive tool for future clinical studies on the prevention of toxic and traumatic renal impairment.
REFERENCES
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