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Prevention of contrast‐media–induced renal impairment by adenosine antagonists in humans
Author(s) -
Erley Christiane M.,
Osswald Hartmut
Publication year - 1998
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/(sici)1098-2299(199811/12)45:3/4<172::aid-ddr13>3.0.co;2-n
Subject(s) - adenosine , vasoconstriction , renal function , renal blood flow , kidney , renal circulation , vasodilation , adenosine receptor antagonist , adenosine receptor , medicine , afferent arterioles , endocrinology , chemistry , pharmacology , blood pressure , angiotensin ii , receptor , agonist
Radiographic contrast media (CM) application causes a decline in renal function (RCIN), especially in patients with preexisting renal dysfunction. Next to hydration, a number of vasodilating substances have been evaluated to prevent renal damage after CM application. On the basis of animal experiments, adenosine has been suggested as a possible candidate for mediating renal vasoconstriction after CM administration. Adenosine is produced in the kidney as a result of an ATP. The assumption that adenosine might have a causal role in the renal function impairment is derived from the observation that adenosine can induce afferent arteriolar vasoconstriction and a fall in glomerular filtration rate (GFR) after intrarenal infusion in rats and dogs. This renal vascular response is unique because other vascular beds react to adenosine with vasodilation. It has been shown that adenosine excretion by the kidney is increased after CM administration. Adenosine could be detected in substantial amounts in the kidney of patients with RCIN. Animal experiments and small clinical trials in patients with normal renal function have demonstrated that the adenosine receptor antagonist theophylline mitigates the CM‐induced fall in GFR and renal blood flow. Dipyridamole, an inhibitor of adenosine uptake, potentiated DM‐induced vasoconstriction. Thus, there is convincing evidence that adenosine is involved in the etiology of RCIN. In a prospective, randomized, double‐blind study, we wanted to assess the efficacy of hydration without (placebo) and with theophylline to prevent RCIN in patients at high risk. It was found that the glomerular filtration rate was not reduced by hydration (3,000 ml starting 24 h before CM application) alone in these patients. The application of theophylline did not bring along an additional benefit. The use of adenosine antagonists may be beneficial in patients in whom sufficient hydration may be impossible or in patients with a concomitant decrease of renal blood flow (e.g., congestive heart failure) and in whom the renin‐angiotensin system is stimulated. This hypothesis is underlined by the observation that theophylline administration in the intensive care unit shows good results regarding the incidence of acute renal failure in patients with cardiac insufficiency. Drug Dev. Res. 45:172–175, 1998.© 1998 Wiley‐Liss, Inc.