These studies were designed to test the hypothesis that adenosine and calcium are important in mediating radiocontrast-media-associated reduction in renal blood flow (RBF) in the dog. Intravenous verapamil (V) and diltiazem (DTZ) infusion significantly attenuated the magnitude of the vasoconstrictor response observed after each intrarenal contrast media (CM) injection. (First injection: -47 ± 8% control vs. -14 ± 3% V, p < 0.03; -38 ± 4% control vs. -19 ± 3% DTZ, p < 0.02. Second injection: -33 ± 6% control vs. -12 ± 1 % V, p < 0.03; -32 ± 5% control vs. -17 ± 2% DTZ, p < 0.03. Third injection: -32 ± 6% control vs. -11 ± 5% V, p < 0.03; -38 ± 5% control vs. -10 ± 5% DTZ, p < 0.02.) Furthermore, V and DTZ almost completely abolished the increase in renal vascular resistance (RVR) induced by each CM administration. Theophylline also significantly attenuated the magnitude of the vasoconstrictor response observed after CM injection (first injection: -31 ± 3% control vs. -12 ± 3% theophylline, p < 0.05; second injection: -26 ± 3% control vs. -12 ± 3% theophylline, p < 0.03). Similarly, theophylline blunted the increase in RVR induced by CM injection. In addition, theophylline inhibited exogenous adenosine-induced decrease in RBF (-61 ± 10% and -26 ± 1 % decrease in RBF without and with theophylline, respectively). In contrast, dipyridamole significantly enhanced the vasoconstriction induced by CM (first injection: 25 ± 3% control vs. 49 ± 4% dipyridamole; second injection: 31 ± 3% control vs. 48 ± 4% dipyridamole p < 0.05). The effect of dipyridamole was abolished by simultaneous theophylline infusion. The vasoconstriction-induced CM was also enhanced during an ischemia (41 ± 11 vs. 28 ± 9%) induced by a reduction in renal perfusion pressure with an aortic clamp. Our data support the contention that endogenous adenosine and calcium action are essential for the effect of CM on RBF. We suggest that infusion of hypertonic radiocontrast agents result in an increase in sodium transport as has been documented with infusion of hypertonic saline with subsequent intrarenal generation of adenosine and activation of calcium-dependent vasoconstriction. Furthermore, our results in the ischemic kidney may explain why CM-induced acute renal failure occurs mainly in patients with preexisting renal failure.
The effect on renal function and efficacy of the angiotensin II AT 1 -receptor blocker (ARB), telmisartan, were compared with those of the angiotensin-converting enzyme inhibitor, enalapril, for the treatment of mild-tomoderate hypertension (diastolic blood pressure [DBP] 95-114 mmHg) in the presence of moderate renal failure (creatinine clearance [Ccr] 30-80 ml/minute). The study was multicentre, double-blind, double-dummy and active-controlled in design, with patients randomised in a 2:1 ratio to receive telmisartan or enalapril. After a two-week placebo run-in period, the 71 eligible patients received either telmisartan, 40 mg, or enalapril, 10 mg, once-daily for four weeks. Thereafter, doses were titrated to telmisartan 80 mg or enalapril 20 mg once-daily if supine trough DBP was still ≥90 mmHg. After a further four weeks, dose titration was again performed, as required, to telmisartan, 80 mg, or enalapril, 20 mg, or frusemide was given in addition if the double dose was already being administered. Mean Ccr decreases of 4.6% for telmisartan and 2.8% for enalapril were not clinically significant. Adverse events occurred in 12 (26.7%) telmisartan-treated patients and in 12 (46.2%) patients receiving enalapril. The mean reduction in supine trough DBP from baseline to the last available value was 12.5 mmHg for telmisartan, compared with 11.9 mmHg for enalapril. A full (reduction of ≥10 mmHg) or partial (reduction of 7-9 mmHg) response occurred in 78% of telmisartan patients and 65% of enalapril patients. In the enalapril group, 43% of patients required frusemide, compared with 29% of those in the telmisartan group. In conclusion, telmisartan lacks detrimental effect on renal function, is effective in the treatment of mild-to-moderate hypertension in patients with moderate renal failure, and is comparable to enalapril.
We have compared the renal effects of ioxitalamate, ioxaglate, and iopamidol in patients with chronic renal failure. Sixty consecutive patients with an estimated creatinine clearance (ECRCl) < 60 ml/min were randomly assigned to receive either ioxitalamate, iopamidol, or ioxaglate. All patients received 500 cm3 isotonic saline before the procedure. Serum creatinine and ECRCl were estimated before, 1 and 2 or 3 days after the procedure. There was no statistical difference between the three groups with respect to age, sex, weight, renal function, amount of iodine, and type of procedure. Mean serum creatinine and ECRCl remained unchanged after administration of contrast media. No patient had nephrotoxicity or acute oliguria requiring dialysis as a result of the administration of contrast material. The number of patients with an increase in the serum creatinine level > 10% from the basal value did not differ in the treatment groups. The maximal increases in serum creatinine were 52 µmol/l (29%) in the ioxitalamate group, 56 µmol/l (18%) in the ioxaglate group, and 57 µmol/l (23%) in the iopamidol group (p = NS). Using a population carefully randomized and matched for renal insufficiency, we could not show any differences in nephrotoxicity between these three contrast agents. Clinically serious renal impairment was uncommon in our study, regardless of the contrast agent used. However, the interpretation of these favorable findings requires a cautionary note. All patients in this study were well hydrated before and after uro-/angiography, and none had a recent renal injury or a treatment with a nephrotoxic agent that would predispose to injury from contrast material. Furthermore, these results cannot be validated without further studying patients with terminal renal failure or patients with low cardiac output and congestive heart failure who cannot bear the risk of being even slightly overhydrated.
The renal hemodynamic and tubular effects of S10036 (fotemustine) were evaluated in seven patients with advanced malignancy. Initial evaluation carried out prior to treatment and repeated 1 day after the first fotemustine infusion and 7 days after the second included clinical, haematological parameters, liver-function tests, and determination of the glomerular filtration rate, renal blood flow and enzymuria. The glomerular filtration rate was 108 +/- 3.7 ml/min before treatment and remained stable after the first (117 +/- 5 ml/min) and second (124 +/- 6 ml/min) fotemustine infusions. Renal blood flow and urinary beta 2-microglobulin and N'-acetylglucosaminidase excretion were also not modified by fotemustine administration. We conclude that fotemustine does not acutely alter renal haemodynamics, nor does it have direct tubular toxicity.
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