Urinary excretion of vasoactive substances in chronic renal failure.

To investigate the pathophysiological role of vasoactive substances in the progression of chronic renal disease, we measured the 24-hour urinary excretion of prostaglandin 6-keto F1alpha, thromboxane B2, NOx, cGMP and ET-1 in 26 patients with chronic renal failure under conservative treatment and in 40 control subjects. Urinary 6-keto PgF1alpha, TxB2 and cyclic GMP were evaluated by RIA, and ET-1 was assayed by EIA. NOx were evaluated using a colorimetric assay as nitrate/nitrite. Urinary excretion of prostaglandin 6-keto F1alpha averaged 18.1 +/- 20.9 ng/g Ucreat in patients vs. 240.9 +/- 257.3 in controls (p < 0.0001), thromboxane B2 422 +/- 374 ng/g Ucreat in patients vs. 967 +/- 589 in controls (p < 2x 10(-5)), NOx 7.07 +/- 5.54 mg/g Ucreat in patients vs. 9.79 +/- 3.77 in controls (p < 0.01), cGMP 310 +/- 200 pg/g Ucreat in patients vs. 488 +/- 241 in controls (p < 0.001). In contrast, ET-1 urinary excretion was almost doubled in patients (13.45 +/- 5.84 ng/g of Ucreat) in comparison with controls (6.84 +/- 2.81 p < 1x10(-5)). While in control subjects significant correlations between urinary excretions of prostaglandin 6-keto F1alpha and thromboxane B2 (r = 0.69, p < 0.001) or NOx and ET-1 (r = 0.54, p < 0.001) were present, in patients only the relationship between urinary excretions of prostaglandin 6-keto F1alpha and thromboxane B2 (r = 0.53, p < 0.01) was retained. Our data suggest that in the normal kidney a balance between prostaglandin I2 and thromboxane A2, or nitric oxide and endothelin-1 is present, which contributes to hemodynamic regulation and protects this organ from ischemic damage. This balance is abolished in CRF, where a large increment of vasopressor agent endothelin is present, which, joined to a prevalent decrease of prostaglandin I2 synthesis, could contribute to the ischemic and fibrogenetic damage of the kidney, leading to progression of renal disease.

Short-term outcome of diabetic patients in renal replacement therapy.

BACKGROUND: Diabetic nephropathy or diabetes-related nephropathies represents one of the most relevant causes of renal failure in recent years. This complex pathological picture becomes particularly severe as time elapses and after starting renal replacement therapy (RRT). METHODS: In an attempt to investigate the evolution of the major clinical features, a retrospective study was carried out on a cohort of 76 diabetic patients on RRT. Sixty-five have been treated by haemodialysis (HD) and 11 by peritoneal dialysis (CAPD), for at least 1 year. In these patients change in modality of treatment, metabolic control, cardiovascular, and ophthalmological complications, peripheral neuropathy, state of vascular access, and intradialytic complications were surveyed at initiation and after 1 year of treatment. A modified Karnofski's score was utilized, to evaluate the degree of rehabilitation. The comparison of prevalence was evaluated, using Student's t-test for paired samples. RESULTS: After 1 year, 11 patients on CAPD remained on the same type of treatment. Out of 65 patients on standard bicarbonate HD, 11 were moved to acetate free biofiltration, two to paired filtration dialysis and one to haemofiltration. A worsening in arrhythmias was recorded with an increased prevalence from 25.0 to 35.0% (n.s.), and one more patient (15 vs 16 and 19 vs 20 respectively) experienced ischaemic cardiomyopathy and cerebrovascular insufficiency. Hypertension showed a significant improvement (72 vs 42, P<0.01). Nausea and vomiting, hypotensive episodes, and muscular cramps were more frequently observed. A worsening in patient's welfare was also recorded but without statistical significance. CONCLUSIONS: This clinical evaluation even if retrospective and lasting 1 year, may suggest that RRT does not per se represent a cause of the development and progression of the major complications related to diabetic disease.

Beta 2-microglobulin removal by synthetic dialysis membranes. Mechanisms and kinetics of the molecule.

Beta 2-microglobulin (beta 2-m) accumulation represents a possible complication of long term dialysis. It is therefore important to evaluate the capacity of removal of this molecule from the patient by different dialysis membranes. The present study is aimed at evaluating the mechanisms involved in beta 2-m removal by three different synthetic membranes: a) highly asymmetric hydrophobic polysulfone (Biosulfane, NMC), b) moderately asymmetric and hydrophobic polysulfone (PS600, Fresenius), c) Polyacylonitrile (AN69HF, Hospal). The adsorption capacity and sieving coefficients of the three membranes for native and labeled beta 2-m were studied in vitro utilizing human blood. The amount adsorbed by the membrane was measured by the elution of the molecule obtained with a detergent solution. Clearances, total removal and membrane adsorption were studied in six patients treated in a randomized sequence with the three membranes. For this purpose, plasma and dialysate measurements as well as total collection of spent dialysate and beta 2-m elution from the used dialyzers were carried out. Ex novo generation of beta 2-m did not take place during in vitro circulation. The molecule was removed by the studied membranes both by filtration and adsorption. The Biosulfane membrane removed beta 2-m mostly by adsorption while the PS600 membrane removed beta 2-m almost entirely by filtration. Intermediate behaviour was shown by AN69 membrane. Similar quantities of beta 2-m were removed from the patients with the three membranes. Total removal could only be precisely measured by adding the quantity of beta 2-m eluted from the membrane to the amount recovered in the spent dialysate. Out of total removal, adsorption was more than 90% with Biosulfane, while only 5% with the PS600. These findings contribute to the understanding of the discrepancy found between the clearance measured from the plasma side and that measured from the dialysate side. In conclusion, clearance and sieving measurements for beta 2-m cannot be correctly performed unless the capacity of adsorption of the membrane is taken into account.

[Influence of droperidol on the hypnotic effect of thiopental]. / Influence du dropéridol sur l'effet hypnotique du thiopental.

We studied the effect of DBP on thiopentone hypnosis in 580 patients aged 20 to 30 and 560 patients aged 40 to 50. The hypnotic effect of thiopentone was evaluated after 5, 15, 30, 45 and 60 minutes from intravenous administration of 0.05 mg.kg-1 of DBP by using dose-effect curves to identify the ED50 dose. The ED50 value of thiopentone decreased up to 15 minutes after DBP (about 1.1 mg.kg-1 in both age groups) and increased after 30, 45 and 60 minutes, the increase being higher in the patients aged 40 to 50. We concluded that DBP has a synergic effect with thiopentone and the pharmacokinetic and alpha 1-lytic effects of DBP are responsible of an increased need of barbituric in the patients aged 40 to 50.