Adenosine and extracellular volume in radiocontrast media-induced nephropathy

Adenosine and extracellular volume in radiocontrast media-induced nephropathy. Renal hemodynamic changes could play a key role in radiocontrast media-induced nephropathy (RCIN), although the pathophysiological mechanisms are unclear. We investigated the role of adenosine in RCIN caused by sodium diatrizoate (Urografin, 3 ml/kg) in nitro-L-Arg methyl ester (L-NAME)-hypertensive rats in different hydration states [eight weeks of L-NAME (50mg/liter) in drinking water; high or low sodium intake for the last two weeks]. In clearance experiments under thiobutabarbital anesthesia in these previously mentioned animals, glomerular filtration rate (GFR), renal blood flow (RBF), and mean arterial pressure (MAP) were measured in the presence or absence of the adenosine A1-receptor antagonist 8-cyclopropyl-1,3-dipropylxanthine (DPCPX, 100 μg/kg bolus plus 10 μg/kg/hr). DPCPX or pretreatment did not change control hemodynamics. Contrast medium caused GFR and RBF to fall significantly in volume-depleted rats (from 0.29 ± 0.02 to 0.21 ± 0.02 ml/min/100g and 5.4 ± 0.3 to 4.0 ± 0.4 ml/min, respectively) without change in MAP. In volume-expanded rats, changes were not significant (0.25 ± 0.01 to 0.24 ± 0.02 ml/min/100g and 5.6 ± 0.3 to 5.3 ± 0.4 ml/min, respectively). In the volume-depleted rats, changes were prevented by DPCPX (0.27 ± 0.02 to 0.24 ± 0.02 ml/min/100g and 4.8 ± 0.1 to 5.0 ± 0.1 ml/min, respectively). The acute hemodynamic effects elicited by contrast medium in L-NAME hypertensive rats thus can be prevented by volume expansion. Adenosine, via A1-receptors, contributes to the adverse effects of contrast media

The ACTIVE trial: Comparison of the effects on renal function of iomeprol-400 and iodixanol-320 in patients with chronic kidney disease undergoing abdominal computed tomography

BACKGROUND: We performed a multicenter, double-blind, randomized, parallel-group study to compare the renal effects of iomeprol-400 and iodixanol-320 in patients with preexisting chronic kidney disease undergoing contrast-enhanced multidetector computed tomography of the liver. METHODS: One hundred forty-eight patients with moderate-to-severe chronic kidney disease, ie, serum creatinine (SCr) ≥1.5 mg/dL (132.6 μmol/L) and/or calculated creatinine clearance (CrCl) <60 mL/min, undergoing contrast-enhanced multidetector computed tomography of the liver were randomized to equi-iodine doses (40 gI) of either the low-osmolar agent iomeprol-400 (400 mgI/mL, 726 mOsm/kg, N = 76) or the isotonic agent iodixanol-320 (320 mgI/mL, 290 mOsm/kg, N = 72), injected intravenously at 4 mL/S, followed by a bolus of 20 mL normal saline solution at the same rate. SCr was obtained at screening, baseline and at 48 to 72 hours postdose. SCr measurements and CrCl calculations were performed by a central laboratory. Contrast-induced nephropathy (CIN) was defined as an absolute SCr increase of ≥0.5 mg/dL (44.2 μmol/L) from baseline to 48 to 72 hours postdose. Mean SCr changes from baseline were also assessed. A Renal Safety Review Board comprised 3 medical experts reviewed the renal safety data, demographics, medical history, CIN risk factors, concomitant medications, and hydration status of each subject in a blinded manner. RESULTS: The 2 study groups were comparable with regard to age, gender distribution, concomitant nephrotoxins, hydration status, and total iodine dose; however, the iomeprol-400 group showed a significantly higher proportion of patients with diabetes mellitus (P = 0.02). Baseline SCr was 1.7 ± 0.6 mg/dL (150.3 ± 53.0 μmol/L) in the iomeprol-400 group and 1.7 ± 0.7 mg/dL (150.3 ± 61.9 μmol/L) in the iodixanol-320 group (P = 0.87). Predose CrCl was 41.5 ± 13.1 mL/Min in the iomeprol-400 group and 43.0 ± 13.3 mL/Min in the iodixanol-320 group (P = 0.49). Five of 72 patient receiving iodixanol-320 (6.9%) and none of the patients receiving iomeprol-400 showed an increase of ≥0.5 mg/dL (44.2 μmol/L) from baseline [P = 0.025, 95% CI (-12.8%, -1.1%)]. The mean SCr change from baseline was significantly higher (P = 0.017 ANCOVA) after iodixanol-320 (0.06 ± 0.27) than after iomeprol-400 (-0.04 ± 0.19). CONCLUSIONS: The incidence of CIN was significantly higher after IV administration of iodixanol-320 than iomeprol-400. The mean rise in SCr from baseline was also higher in patients receiving iodixanol. © 2008 Lippincott Williams & Wilkins, Inc