Kidney preservation with IGL-1 solution: a preliminary report.

The University of Wisconsin (UW) solution is the most commonly used preservation solution. However, a new preservation solution-IGL-1-contains an inversion of K and Na concentrations and substitution of polyethylene glycol for hydroxyethyl starch in the UW solution. The present study is the first clinical experience on the outcome of kidneys preserved in IGL-1 solution. From June 2003 to June 2004, 119 cadaveric kidneys were retrieved and stored in IGL-1 solutions; among the 119 organs, this study includes 37 IGL-1-preserved kidneys that were locally transplanted versus 33 kidneys stored in University of Wisconsin (UW) solution that were also locally transplanted. The groups were comparable with regard to donor and recipient characteristics. Renal function outcome was evaluated by comparing delayed graft function (DGF) rates, the evolution of serum creatinine, daily urine output, and creatinine clearance. Biopsies were performed after reperfusion to evaluate apoptosis. The incidence of DGF was 5.71% among IGL-1 kidneys and 13.79% among UW kidneys. Creatinine values were significantly lower among the IGL-1 group from 2 to 14 days postoperative and at 1 month. Daily urinary output did not show any significant differences between the two groups. IGL-1 kidneys had a superior creatinine clearance during the first 15 postoperative days compared to UW kidneys. Kidneys preserved in IGL-1 solution showed fewer apoptotic cells compared to kidneys preserved in UW solution. This preliminary report suggests a superiority of IGL-1 for the immediate outcome of transplanted kidneys.

Adrenergic stimulation of renal prostanoids in the Lyon hypertensive rat.

Young, genetically hypertensive Lyon (LH) rats exhibited an increased renal in vivo turnover of norepinephrine and an elevated urinary excretion of thromboxane B2 when compared with normotensive (LN) and low blood pressure (LL) controls. Therefore, the effects of norepinephrine (1.2 x 10(-8) to 9.6 x 10(-7) M) and of phenylephrine (5 x 10(-8) to 1.9 x 10(-6) M) on renal function and the urinary excretion of prostanoids were assessed in isolated perfused kidneys of 8-week-old LH, LN, and LL rats. In addition, the effects of norepinephrine were assessed before and during thromboxane A2/prostaglandin H2 receptor blockade by AH23848 (4 x 10(-6) M). Before drug infusion, LH kidneys differed from those of LN and LL controls by having an elevated renal vascular resistance and a decreased natriuresis and glomerular filtration rate; the urinary output of prostaglandin E2 and F2 alpha, of 6-ketoprostaglandin F1 alpha, and of thromboxane B2 was similar in the three strains. The constrictor effects of norepinephrine and phenylephrine were significantly increased in LH rat kidneys compared with LL but not with LN controls, and their pressure-natriuresis was markedly reduced. Norepinephrine and phenylephrine induced a 10- to 20-fold dose-dependent increase in the synthesis of the four prostanoids, which was more pronounced in LH than in LN and LL rats for thromboxane B2 only. AH23848 infusion significantly reduced the vascular effects of norepinephrine and increased the natriuretic response of LH but not of LN and LL rat kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal thromboxane A2 synthesis in the Lyon hypertensive rat.

The aim of the present study was to assess the mechanisms by which norepinephrine (NE) increased the synthesis of prostanoids and revealed a hyperactivity of the Thromboxane (Tx) A2 synthase in the Lyon genetically hypertensive (LH) rat kidney. To this purpose, the effects of NE (1.2 x 10(-8) to 9.6 x 10(-7) M) on renal function and prostanoid synthesis were assessed in isolated perfused kidneys following beta-adrenoceptor blockade by sotalol (10(-5)M) and compared to those of equipressor concentration of an alpha 2-adrenoceptor agonist, BHT 933 (3.5 x 10(-4) M) and angiotensin II (AII) (7.7 x 10(-9) M). Kidneys were isolated from eight week-old male LH rats and from their normotensive (LN) and low blood pressure (LL) controls and perfused in a single pass system. In baseline conditions, sotalol did not modify renal function or urinary prostanoids in any of the three strains. Following NE stimulation, it potentiated the increase in renal vascular resistance of LL and LN controls but not that of LH rats. The pressure-natriuresis and the urinary prostanoids remained unchanged. BHT 933 elicited a weak stimulation of prostanoid release while AII markedly increased it and revealed, as did NE, the hyperactivity of the TxA2 synthase. It is concluded that the NE-induced stimulation of prostanoid synthesis does not involve beta-adrenoceptors and is unrelated to the associated hemodynamic changes. These results also demonstrate that the increased renal synthesis of TxA2 observed in LH rat kidney is not a specific response to alpha-adrenoceptor stimulation and is likely to involve activation of the phosphoinositide pathway.

[Comparative effects on renal function of 4 beta-blockers injected intravenously]. / Effet comparé sur les fonctions rénales de quatre beta-bloquants injectés par voie veineuse.

Four beta-blockers: atenolol 15 mg i.v., metoprolol 25 mg i.v., acebutolol 45 mg i.v. and labetalol 50 mg i.v. were administered to 106 patients suffering from hypertension and with normal or disturbed renal function. During an identical test protocol, measurements of clearance of inulin, of PAH, urine sodium and the fraction of sodium excreted were recorded one hour before and four or five hours after administration of the antihypertensive. Mean blood pressure and heart rate were also recorded. The three pure beta-blockers reduced inulin and PAH clearance and lowered urine sodium. These modifications were the same for all three drugs. Labetalol, which also possesses alpha-blocking properties, did not reduce renal function values or urine sodium. While a slight fall in blood pressure occurred with all the antihypertensives, heart rate was reduced only by the three pure beta-blockers. The action of the four drugs was very similar whatever the state of the subject's renal function. The study of the renal effects of the beta 1-selective atenolol and metoprolol, and acebutolol which has a higher intrinsic sympathomimetic activity does not demonstrate any significantly different renal action among these three drugs, but the effects of labetalol on renal function values and urine sodium are slighter. The renal action of the beta-blockers cannot be fully explained. Though the fall in the renal plasma flow and in the glomerular filtration rate can be related partly to the decrease in the cardiac output consequent to induced bradycardia, stimulation of renal alpha-receptors must be considered.(ABSTRACT TRUNCATED AT 250 WORDS)

Uric acid renal handling: spontaneous changes and influence of a thiazide alone or associated with triamterene.

The spontaneous changes in renal handling of uric acid, the consequences of methyclothiazide (M) and of a combination of M with three doses of triamterene (25, 50, 75 mg) were assessed in eight normal men, in a ten-week placebo controlled, double-blind study. In untreated subjects, significant correlations were found between blood uric acid (bUA) and UAV, between bUA and FeUA, between FeUA and plasma renin activity (PRA) and between bUA and PRA. Spontaneous variations in bUA and UAV were shown to be predominantly dependent on changes in sodium status. All diuretics significantly increased bUA and decreased FeUA. Under diuretics, bUA kept correlations with FeUA and PRA similar to that observed in untreated subjects indicating that the changes were dependent only on variations in renal transport induced by changes in sodium status. Addition of triamterene to methyclothiazide significantly lessened the thiazide induced abnormalities in UA.

Influence of treatment by betaxolol on the renal response to postural changes in moderate hypertension.

Assumption of upright posture is known to be associated with significant variations in renal function, which are thought to be mediated through the stimulation of the renin angiotensin system. The effect of an eight-week treatment with betaxolol, a selective beta-blocker, was studied in patients with moderate hypertension and normal renal function. Betaxolol induced the expected changes in systemic hemodynamics and reduced supine plasma renin activity and aldosteronemia. The glomerular filtration rate showed no variation but the tubular reabsorption of sodium increased. The renal adaptation to postural changes (decrease in glomerular filtration rate, increase in sodium reabsorption and in plasma renin activity) was unaffected by treatment. It is concluded that betaxolol does not impair the renal response to a physiological stimulus such as change in posture.

Pharmacokinetics of diltiazem in severe renal failure.

The acute effects of a single dose of diltiazem (Tildiem), a calcium antagonist, were studied in 9 patients with severely impaired renal function (GFR between 0.03 and 0.87 ml/s/1.73 m2). Control measurements were made of inulin and PAH clearance, creatinine, blood pressure, heart rate and ECG. Following administration of diltiazem 120 mg, 7 blood samples were collected in the first 12 h and after 24 h, 32 h, 48 h; urine was collected for the first 12 h, 12-24 h and 24-48 h, and blood pressure, heart rate and ECG were recorded after 6 h. Diltiazem and its main metabolite, desacetyldiltiazem, had a pharmacokinetic profile similar to that in patients with normal renal function (peak plasma concentration, half-life and urinary excretion). Diltiazem is normally eliminated in the urine to a small extent, because it is metabolized, and this also applies to desacetyldiltiazem, which is probably further metabolized.