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Biomedical subjects

N Pozet

Publications and source records attributed to N Pozet.

At least 73 records · Page 4Linked to original sources

Magnesium in kidney diseases. A review.

During the last decades the kidney has emerged as a key organ in the homeostasis of magnesium and disturbances of magnesium metabolism have been described in several renal diseases. Restoring body stores to normal levels should be one of the goals in the conservative treatment of end stage renal failure, since magnesium retention is thought to participate in uraemic toxicity. The kidney is also the target organ of many drugs and increased magnesium excretion can be observed either as an obligatory side effect or as a sign of nephrotoxicity. Magnesium depletion could participate in the vascular complications observed with such drugs. The significance of hypomagnesaemia in Bartter's syndrome remains obscure. Renal stone disease is frequently associated with a low urinary magnesium output, although the determinants of this abnormality are still not well understood.

Animals↗

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.

Adult↗

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.

Adult↗

Magnesuria induced by thiazides and the influence of triamterene.

The effects on magnesium excretion of 4 short-term diuretic treatments (methyclothiazide 2 mg either alone or associated with increasing doses of triamterene) were evaluated in 8 normal volunteers and compared to spontaneous variations during placebo administration. The thiazide exerted a small but significant magnesuric effect, which was prevented only by the lowest dose (25 mg) of triamterene. Larger doses had no protective effect on thiazide-induced magnesuria. Independently of their absolute effects on magnesium excretion, all diuretics impaired the normal ability of the kidneys to compensate fully for the expected changes in magnesium reabsorption induced by extracellular volume contraction.

Adult↗

Pharmacokinetics of teicoplanin in renal failure.

By using a highly specific chromatographic technique, the effect of renal failure on the pharmacokinetics of the six main components of teicoplanin, taken individually or as a whole, was assessed for over 120 h after administration of a 3-mg/kg intravenous dose to healthy volunteers (group 1, n = 6) and to noninfected patients with moderate (group 2, n = 6) or severe (group 3, n = 7) renal failure. In subjects with normal renal function, total teicoplanin was mainly excreted in urine and its concentrations in plasma could be adequately fitted to a three-compartment model. Renal failure did not affect the model or the distribution of teicoplanin but strongly decreased its renal clearance (9.3, 3.2, and 0.6 ml/h per kg, respectively, for the three groups of subjects), in close relationship with the creatinine clearance (r = 0.973, n = 18, P less than 0.001). The cumulative urinary excretion of unchanged total teicoplanin was decreased (50, 21, and 5% of the given dose for groups 1 to 3) and the terminal half-life was enhanced (62, 96, and 111 h for groups 1 to 3) by renal impairment. The relative behavior of the six major components was only slightly affected by renal failure. Consequently, the dosage regimen adjustment could be based on the total teicoplanin concentration, and simulations with the mean estimated pharmacokinetic parameters suggest that the 6-mg/kg daily dose, known to be effective in patients with normal renal function, could be given every 2 and 3 days in patients with moderate and severe renal insufficiency, respectively.

Adult↗

[Influence of acute administration of ramipril on the excretion of uric acid].

The influence of a new ACEI, Ramipril (R) on renal handling of UA was investigated. 13 hypertensives with normal renal function received either R (10 mg p.o.) or placebo (P). Arterial pressure (AP), GFR (Inulin clearance), Renal Plasma Flow (RPF, PAH clearance), UA urinary excretion (UAV) and fractional clearance (FeAU: UA clearance/GFR) were studied for seven hours after drug administration. GFR remained stable in all cases. R had no effect on sodium excretion rate. Compared to P, R significantly increased UAV by 25 p. 100, FeAU by 32 p. 100, RPF by 26.5 p. 100 and decreased mean arterial pressure (MAP) by 10 p. 100. ACE activity was maximally suppressed at 2 hours. More than 80 p. 100 of the maximal changes in UAU and FeAU were observed within the first two hours, while a progressive increase in RPF up to the fifth hour, and a progressive fall in MAP up to the fourth hour was evident. Except for PAM, all these changes were still present at the end of the study (seventh hour). In conclusion, Ramipril increases the fractional excretion of uric acid. This effect is observed independently of any change in sodium balance and preceeds by two to three hours the changes in renal hemodynamics. The simultaneous changes in FeAU and in ACE activity indicate that the effect on uric acid excretion is presumably due to the fall in angiotensin concentration.

Angiotensin-Converting Enzyme Inhibitors↗

[Pharmacokinetics of ceftriaxone in hemodialysis].

The influence of hemodialysis on the pharmacokinetics of ceftriaxone was studied in 5 patients with chronic renal failure, with a glomerular filtration rate of less than 5 ml/min, and treated by regular hemodialysis. A single dose of 2 g ceftriaxone was administered IV at the end of a hemodialysis, and venous samples were drawn 12 and 24 h thereafter. Two hemodialysis were performed at the 44th (HD1) and the 92nd (HD2) hour, and blood samples were drawn simultaneously on arterial and venous sides of the dialyzer at the onset of HD1 and at the end of HD2. Plasma ceftriaxone concentrations were measured on each sample by both microbiological and chromatographic (HPLC) methods. In these patients, ceftriaxone kinetics are considerably longer than in normal subjects, with an elimination half-life of 16 h, an apparent distribution volume of 800 ml/kg, but without decrease of plasma clearance, except in one patient who had hepatic cytolysis at the time of injection. Plasma concentrations on both sides of dialyzers, or before and after hemodialysis, are not significantly different, and the mean hemodialysis clearance ranges between 26 and 30 ml/min/m2 dialyzer area. According to these data, the dose-interval between successive administrations of ceftriaxone 2 g IV should be 48 h in patients with chronic renal failure, and supplemental doses do not appear necessary after hemodialysis.

Adult↗

Evolution of renal function under chronic oral administration of labetalol.

The glomerular filtration rate (GFR, inulin clearance) and renal plasma flow (RPF, PAH clearance) were measured in 35 hypertensive patients during chronic administration of an alpha-beta-blocker, labetalol. No significant changes in GFR occurred but RPF increased significantly. The increase in RPF was positively correlated with the decrease in mean arterial blood pressure. Patients with renal failure showed changes similar to patients with normal renal function. Thus chronic treatment with labetalol, unlike most beta-blockers, can increase RPF, an effect which could be related to the alpha-blocking activity of the drug.

Administration, Oral↗

Acute renal effects of beta-blockers.

The effects on renal function of a single dose of six different beta-blockers (atenolol, propranolol, metoprolol, acebutolol, nadolol, and pindolol) have been evaluated in 51 hypertensive patients with normal glomerular filtration rate (GFR). Most drugs, except pindolol, induce a 10-20% decrease in GFR and renal plasma flow, although differences in the magnitude and the pattern of this fall are evident. The fractional excretion of sodium is generally depressed by 20-40%. These data suggest a limited renal tolerance of most beta-blockers during acute administration, irrespective of their pharmacological characteristics.

Adrenergic beta-Antagonists↗

Surgical versus medical treatment in renovascular hypertension. Retrospective study of 166 cases.

A retrospective study of 166 cases of renovascular hypertension was performed. Before 1979, 114 patients were treated for renovascular hypertension. Forty underwent surgery. In this group, therapy resulted in cure or improvement in 45% of the patients. Seventy-four patients underwent medical therapy: 88% of these patients had improvement of blood pressure when beta-blockers were used, but only 41% when they were not. More recently (from 1979 to 1983), 52 patients were treated for renovascular hypertension, of which 31 patients have been operated for fibromuscular renal artery stenosis (62%) or atherosclerotic renal artery stenosis (32%). In this group, 90% of the patients were considered to be cured or improved with a mean follow-up of 36 months. Eighteen of thirty-one patients underwent autotransplantation with satisfactory results on blood pressure control. Twenty-one patients were treated by antihypertensive drugs: 86% of the patients were improved or cured (71.5% of the patients had atherosclerotic lesions) with a mean follow-up of 46.8 months.

Adult↗

Pharmacokinetic studies of standard heparin and low molecular weight heparin in patients with chronic renal failure.

The disappearance of the anticoagulant activities of a standard commercial heparin and of a low molecular weight (LMW) heparin (PK 10169), administered as single intravenous injections, was studied in patients with chronic renal failure. Heparin and LMW heparin anticoagulant activities were determined by activated partial thromboplastin time (APTT) and chromogenic assays of anti-Xa and anti-IIa activities. Following heparin injection, a fast initial decay of anticoagulant activities preceded a slow convex disappearance curve, in semilogarithmic plots. These experimental data are in agreement with a model based on a predominant saturable mechanism of elimination of heparin in patients with renal failure. The disappearance of LMW heparin anti-Xa activity was obviously different, with linear or concave elimination curves, and longer apparent half-life. Taken together, our kinetic data and those previously reported in normal subjects strongly suggest that the mechanism of elimination of the LMW heparin studied is not saturable (at least for the tested dosages), and that the kidneys play a minimal role in the elimination.

Adolescent↗

[Course of renal function in malignant hypertension. Effect of treatment. Study of 30 cases followed for 5 to 18 years].

Renal insufficiency is the most frequent complication of malignant hypertension (MHT). The initiation of effective hypotensive treatment is generally followed by a rapid improvement of renal functions, but the long-term evolution has been only rarely studied. A group of 30 patients was retrospectively selected on the following criteria: Malignant hypertension: mean DBP 138 +/- 20 mmHg, hypertensive retinopathy stage III-IV; Early renal insufficiency: mean Inulin clearance (CIN) 66 +/- 26 ml/min, mean PAH clearance (CPAH) 364 +/- 161 ml/min; Clinical and functional follow-up ranging from 5 to 18 years. Among these patients, two groups were defined according to the quality of BP control: good or fair responders (GR) with a DBP always less than 110 mmHg, poor responders (PR) with a DBP occasionally greater than or equal to 110 mmHg. The results show in the two groups an improvement of CIN at 3 years, followed by a stabilization then a decrease after the 6th year. However the early improvement is significantly lower in PR. Despite similar initial values (GR = 54.7 +/- 31.3; PR = 51.4 +/- 13.2), CIN remains always lower in PR (at 9 years = GR 72.4 +/- 30.6; PR 56.0 +/- 19.8). During the first 3 years, CPAH increases in GR, whereas it decreases in PR, resulting in significantly different values at 3 years. At 9 years, CPAH remains improved in GR (329.1 +/- 109.3 vs 281.7 +/- 173.8 initially) but decreased in PR (256.0 +/- 166.9 vs 307.3 +/- 119.5 initially). The parallel improvement of CIN and CPAH in GR confirms a favorable effect of BP control on early vascular lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Influence of renal failure on the kinetics of zimeldine and norzimelidine.

The kinetics of zimeldine (Z) and its demethylated metabolite, norzimelidine (NZ), were determined after administration of a single 200 mg oral dose of Z to 6 healthy volunteers (Group I), and to patients with mild (Group II) and severe renal failure (Group III). Z and NZ concentrations were assayed by HPLC in serial plasma and urine samples over 6 days following the dose. In Group I Z was rapidly absorbed and metabolized into NZ, and then the plasma concentrations declined with apparent elimination half-lives of 8.4 h and 24.9 h for Z and NZ respectively, whilst the renal clearance of both compounds was low, Z 15.7 ml/min and NZ 33.0 ml/min. The plasma level of Z differed little between Groups I and III, but the area under the curve was significantly higher in Group III than in Group I subjects (AUC0-144 = 17.3 and 6.8 mumol X l-1 X h, respectively). Severe renal failure did not affect the peak plasma concentration of NZ but it did significantly increase peak time, apparent elimination half-life, and the area under the plasma concentration curve. A significant inverse relationship was found between renal clearance of NZ and plasma creatinine. Since NZ is as pharmacologically potent as Z, the results suggest that the dose of Z should be reduced in patients with severe renal insufficiency.

Adult↗