A preliminary investigation of the nephroprotective effects of the adenosine antagonist aminophylline in patients undergoing abdominal aortic aneurysm repair

Infra-renal clamping of the abdominal aorta during aneurysm repair is associated with a significant reduction in renal blood flow. Adenosine has been implicated as a mediator of renal ischemia in a number of human and animal models and its antagonism with theophylline has lead to the attenuation of these effects. In order to investigate the possible attenuation of renal arterial vasoconstriction associated with infrarenal cross clamping of the aorta we prospectively randomised 8 consecutive patients undergoing abdominal aortic aneurysm repair to receive aminophylline 5 mg/kg (n = 5) in 500 ml normal saline or placebo (n = 3) on the morning of surgery followed by an infusion of 6 mg/hour of aminophylline or placebo for 24 hours. Staff, investigators and patients were blinded. Inulin clearance as an indicator of glomerular filtration rate (GFR) was measured pre-operatively and again on the 2nd post-operative day. N-Acetyl-β-glucosaminidase (NAG) activity (mmol PNP/hour/mol creat) and Retinol Binding Protein (RBP) excretion (mg/mol creat) were measured to assess renal tubular damage and albumin excretion (mg/mol creat) as a marker of glomerular injury.

Results

There was a significant increase between the pre and post operative measurements in NAG activity (45.53 to 248.96, P = 0.0078), RBP excretion (10.68 to 3851.92, P = 0.0078) and albumin excretion (1.165 to 7.88, P = 0.0078) however there was no difference between the treatment and control groups. Contrary to expectation inulin clearance was marginally increased in the postoperative period (80 vs 76 ml/min/1.73 m², P = 0.36) in spite of a significant reduction in urinary volumes (85 vs 40 ml/hour, P = 0.05).

Conclusions

1. Infrarenal aortic aneurysm repair is associated with significant renal ischemia that does not result in a sustained fall in GFR. 2. Urine volumes are not an accurate reflection of GFR in this setting. 3. Measurement of perioperative GFR is not a suitable way to assess the effects of adenosine antagonism in this model of renal ischemia.

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