[The fibrocystic form of hyperparathyroidism of renal origin. Apropos of 2 cases].
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Biomedical subjects
Publications and source records attributed to M Labeeuw.
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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.
Twenty-seven patients with renal vein thrombosis were retrospectively studied to evaluate their long-term prognosis and relevant prognostic factors. Twenty-four patients presented with a nephrotic syndrome, and 15 had renal impairment (8 acute; 7 moderate). Ten patients had a previous history of proteinuria, and 14 of nephrotic syndrome. Renal biopsy performed in 20 patients, of whom 19 were nephrotic, showed membranous glomerulonephritis in 14, focal segmental glomerulosclerosis in three, minimal change glomerulonephritis in two, and periarteritis nodosa in one. Renal vein thrombosis was angiographically proven in all patients and was bilateral in 18, localised to the left renal vein in seven, and to the right in two. Thrombosis of the inferior vena cava was associated in seven patients. Ten patients were treated by anticoagulants alone, nine by surgical thrombectomy, seven by thrombolysis, and two did not receive any specific treatment. One patient underwent successively thrombectomy and then thrombolysis. Eleven patients died within the first 6 months, mainly from haemorrhagic complications (n = 5) or severe sepsis (n = 2). Survivors were followed up from 6 months to 19 years. Nephrotic syndrome improved or even disappeared in 12 patients, and renal function did not worsen throughout the follow-up in any patients. The main prognostic factors were initial renal function and type of nephropathy: patients with membranous glomerulonephritis had a significantly better renal function and a lower mortality rate than patients with other nephropathies. Initial renal insufficiency was significantly associated with a poor prognosis. There was no advantage, in terms of survival, kidney function and nephrotic syndrome, of either thrombectomy or thrombolysis over anticoagulants alone, despite two complete venous recanalisations after thrombolysis. Accordingly, patients with renal vein thrombosis from membranous glomerulonephritis should be treated by anticoagulants alone, since the long-term prognosis of this disease seems unaffected by intercurrent renal vein thrombosis. With respects to the risk-to-benefit ratio, thrombectomy should be avoided and thrombolysis considered only in patients with initial acute renal failure from acute renal vein thrombosis.
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.
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.
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.
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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.
Dissolution of uric acid calculi could be obtained by oral or parenteral urinary alcalinization, but this method cannot apply to the case of obstructive calculi. Nineteen obstructive calculi in 18 patients were treated by in situ alcalinization through a percutaneous nephrostomy catheter (PCN). Eight patients were initially anuric, 7 of whom from an obstructed solitary kidney and 1 from a bilateral obstructive lithiasis. Fifteen calculi were located in the ureter, 3 in the uretero-pelvic junction and 1 in the pelvis. After 48 h of urinary diversion through PCN, an isotonic sodium bicarbonate solution (14 g %) was continuously infused at an average flow rate of 2.8 l/24 h, through either an unique PCN, or a 2 PCN-irrigation circuit in the 7 cases with permanently obstructive calculus. Fifteen calculi (80%) were completely dissolved after 3 to 13 days of alcalinization (average 5.8 days). One large calculus was reduced by 3/4 and further removed by percutaneous lithotripsy. Three patients underwent ureterotomy after 9 to 11 days of uneffective treatment. Local alcalinization is an effective and non invasive treatment for obstructive uric acid calculi, and is logically associated with the necessary urinary diversion.
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.
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.
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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.
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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.
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