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Biomedical subjects

H E Eliahou

Publications and source records attributed to H E Eliahou.

At least 19 recordsLinked to original sources

Successful pregnancy in a patient with polycystic kidney disease and advanced renal failure: the use of prophylactic dialysis.

Adult polycystic kidney disease is an inherited disease that is transmitted as an autosomal dominant trait. The clinical manifestations, which develop during the third or fourth decade of life, usually do not affect women during childbearing age and thus do not affect fertility or pregnancy outcome. The patient presented here had polycystic kidney disease and advanced renal failure, and was treated with meticulous fetal surveillance and prophylactic hemodialysis during pregnancy. The successful outcome strengthens the trend to perform prophylactic dialysis in pregnancies with advanced renal failure, despite the lack of controlled studies.

Adult

Effect of low-calorie diets on the sympathetic nervous system, body weight, and plasma insulin in overweight hypertension.

When weight reduction was found to decrease blood pressure in the overweight hypertensive patient, it was hailed as the causative factor. A growing number of recent studies indicate that this association may be secondary to a correlation between diet-associated metabolic change and the sympathetic nervous system. A select group such as overweight hypertensive patients may have a genetic predisposition for such a correlation. In overweight hypertensive patients, low-calorie diet and especially very-low-calorie diet, correlate with improved glucose metabolism, a decrease in plasma insulin concentration, and altered norepinephrine concentrations and thus sympathetic nervous system activity. Several of these studies also show a lack of effect of salt intake on blood pressure. Thus, it seems that metabolic changes caused by the decrease in caloric intake are responsible for the decrease in blood pressure. These must be investigated to understand the effect of the different diets on blood pressure. Very low-calorie diets were found very useful in breaking the vicious circle of severe nonresponsive hypertension to medication.

Blood Pressure

Effect of nisoldipine on ambulatory blood pressure under 24-hour noninvasive monitoring.

The antihypertensive effect of nisoldipine on ambulatory blood pressure was investigated using continuous noninvasive monitoring in 12 patients with moderate essential hypertension. Treatment with nisoldipine 5 mg twice a day for 2 weeks resulted in a decrease in the average of each patient's mean arterial pressure for the whole day from 110.3 +/- 6.8 to 103.2 +/- 8.8 mm Hg (P = 0.0007). This decrease in mean arterial pressure was due to a decrease in both systolic and diastolic pressures. The reduction in blood pressure was most marked at the time of the originally high blood pressure readings. Comparisons of consecutive means of 2-hourly mean arterial pressure readings showed a statistically significant effect from 6:00 AM to midnight. Blood pressures between midnight and 6:00 AM were similarly low, before and during nisoldipine therapy. There was no change in heart rate. Untoward symptoms were reported with similar frequency, and of similar severity, both before and during therapy. Nisoldipine 5 mg twice a day is an effective antihypertensive agent, reducing moderately elevated blood pressure in ambulatory, working patients with essential hypertension. At the dosage used, it had no demonstrable effect on heart rate and minimal, if any, side effects.

Adult

Calcium channel blocker nisoldipine in chronic renal failure.

Patients with a stable progression of chronic renal failure with a creatinine clearance of 15-45 mL/min were randomly assigned to two groups of antihypertensive therapy: 1--nisoldipine as the only antihypertensive agent and 2--antihypertensive drugs without calcium channel blockers and a placebo tablet instead of nisoldipine. The patients were already on a low-protein diet and some form of antihypertensive therapy but without calcium channel blockers. There were 18 patients in the placebo group and 20 patients in the nisoldipine group. The follow-up period averaged 23.7 +/- 10.6 (SD) months in the placebo group and 23 +/- 11.3 months in the nisoldipine group. The slopes of the reciprocal of serum creatinine were calculated for the period prior to and following our intervention. The number of patients whose slopes improved following intervention was 6/18 in the placebo group and 15/20 in the nisoldipine group (p less than .02). The patients whose slopes improved had a significant fall in systolic and diastolic BP, as well as in the MAP. Those whose slopes did not improve had a significant decrease in systolic BP, but no change in diastolic BP and no significant difference in the MAP. When all 38 patients are analyzed together, regardless of their grouping, the correlation between the difference percent in the slope, and the difference percent in the MAP, was significant. Furthermore, punch biopsies of the skin showed a markedly different calcium content in the two groups, which was significantly less in the nisoldipine-treated patients as compared with the patients not receiving calcium blockers.(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive Agents

Energy restriction or salt restriction in the treatment of overweight hypertension. Which one? A point of view.

Body weight reduction in the overweight hypertensive patient was found to reduce blood pressure, irrespective of the daily urinary sodium excretion. Significant blood pressure reductions were achieved while the urine sodium excretion was between 165-185 mEq/day. Salt restriction resulting in a significant decrease of the 24-hour urine sodium from 192-110 mEq/24-hours did not change the blood pressure. Some of the studies indicating a reduction in blood pressure, did not take into account the changes in body weight, while on sodium restriction. Thus sodium restriction in the treatment of hypertension has not been uniformly found to reduce the blood pressure. Although there is much evidence in favour of the involvement of sodium in the regulation of blood pressure, there is no convincing evidence that dietary sodium restriction can be of use as a therapeutic modality in the treatment of hypertension in the overweight hypertensive patient.

Blood Pressure

The calcium channel blocker nisoldipine delays progression of chronic renal failure in humans (preliminary communication).

Chronic renal failure (CRF) patients with a stable course were asked to participate in a follow-up program in which they were randomized into two groups: 1) the placebo group taking their standard antihypertensive therapy without any calcium ion blocker: and 2) the nisoldipine group, those patients taking the calcium channel blocker nisoldipine as the only antihypertensive drug. The two groups had similar blood pressures on entering the study (151 +/- 21.3/90.7 +/- 7.4 mmHg in the nisoldipine and 146.7 +/- 18/94 +/- 9.4 mmHg in the placebo group). Their protein intake was also similar (daily average throughout the follow-up period: 0.83 +/- 0.18 g protein per kg body weight in the nisoldipine and 0.9 +/- 0.12 g in the placebo group). The patients were checked monthly. The follow-up averaged 11.1 +/- 4.8 months in the nisoldipine group and 13.7 +/- 4.2 months in the placebo group. The rate of progression of CRF, as expressed by the slope of the regression line of 1/serum creatinine versus time, decreased in the nisoldipine group from the initial (-8.03 +/- 4.91) x 10(-3) to (-5.57 +/- 5) x 10(-3) (two-tailed P-test = 0.016) after intervention. The slopes tended to become steeper in the placebo group, with an initial slope of (-4.1 +/- 3.2) x 10(-3) changing to (-7.9 +/- 5) x 10(-3) after intervention. This difference did not reach statistical significance (two-tailed P = 0.072). The rate of progression of CRF decreased in 12 of 14 patients in the nisoldipine-treated group versus 3 of 11 patients in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Effect of the calcium channel blocker nisoldipine on the progression of chronic renal failure in man.

Patients with stable renal insufficiency were randomized into two groups: (1) patients given the channel blocker nisoldipine (n = 17) and (2) placebo-treated patients (n = 17) also taking their regular antihypertensive therapy which did not include calcium blockers. Patients were already on low protein diet with a protein intake of 0.80 +/- 0.2 in the nisoldipine group versus 0.85 +/- 0.25 g/kg body weight in the placebo-treated group. The monthly progression of their renal failure was assessed by the reciprocal of serum creatinine versus time in months. After a mean follow-up of 17.4 +/- 8.2 (range 6-30) months, the nisoldipine-treated group had a significant decrease in their slope of progression, whereas the placebo-treated patients, after 16.94 +/- 7.2 (range 6-30) months of follow-up, had no significant change in their slope. The protein intake during follow-up was similar, being 0.85 +/- 0.2 g/kg actual body weight in the nisoldipine-treated group and 0.88 +/- 0.26 g/kg in the placebo group. The changes in slope did not correlate with the changes in blood pressure.

Adult

The control of hypertension and its effect on renal function in rat remnant kidney.

Blood pressure control and its influence on the rat remnant kidney function were studied. The deterioration in kidney function was followed for up to 20 weeks at 4-weekly intervals in four groups of 5/6th nephrectomised rats. The groups studied were: (1) Control, untreated (C), given normal rat chow containing 21% protein; (2) nisoldipine (a dihydropyridine calcium channel blocker) treated (N), given nisoldipine freshly mixed daily in normal chow (0.3-0.6 mg/kg body weight); (3) dihydralazine-treated (H), fed normal chow and given dihydralazine added daily to the drinking water, about 15-25 mg/kg body weight daily; and (4) low-protein (6%) diet (LP), isocaloric and having the same sodium content as the normal chow. Proteinuria, serum creatinine, blood urea, histological damage as seen by light microscopy, and cumulative survival were taken to assess the severity of the chronic renal failure. All three therapeutic regimens attenuated significantly the rise in blood pressure which developed within less than 4 weeks in the rats with the remnant kidney. At the 16th week, means +/- standard deviations were, in group C, 237 +/- 20 mmHg; group N, 147 +/- 20 mmHg; group H, 164 +/- 23 mmHg; and group LP 149 +/- 16. Systolic blood pressure at the 8th week had a significant correlation with the serum creatinine of the 12th and of the 16th weeks. There was a strong correlation between blood pressure and the serum creatinine at the 16th week. This indicates that a time lag is necessary for the hypertension to have an effect on kidney function. Proteinuria, serum creatinine and blood urea were much higher in the untreated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Dialysis during pregnancy in advanced chronic renal failure patients: outcome and progression.

Successful pregnancies in uremic women are rare. Early initiation of regular hemodialysis in pregnant moderately uremic women is debatable. We chose regular hemodialytic treatments in 2 pregnant patients with stable renal failure with the aim of improving fetal outcome. The first patient with reflux nephropathy arrived at our clinic in the 18th week of her second pregnancy, having a serum creatinine level of 4.5 mg/100 ml and a creatinine clearance (Ccr) of 15 ml/min. Regular hemodialysis was carried out from the 29th gestational week until delivery. A healthy female infant was born weighing 1,095 g at the end of the 36th week of pregnancy. The second patient had an immune complex nephritis with a serum creatinine of 4.2 mg/100 ml and a Ccr of 18 ml/min. Hemodialysis was performed regularly from the 13th gestational week until the 37th week and stopped when normal labor developed and a healthy female infant weighing 2,145 g was born. We believe that the early initiation of regular hemodialysis in these 2 patients contributed significantly to the successful outcome of their pregnancies.

Adult

Relationship between plasma renin activity and distal nephron sodium delivery and reabsorption in man.

The relationship between plasma renin activity and distal tubular sodium delivery and reabsorption was examined in man. Distal sodium delivery and reabsorption were measured during hypotonic volume expansion by the free water clearance method, or during hydropenia or isotonic volume expansion by the lithium clearance method. The maximal water diuresis method and the lithium clearance method both showed a negative correlation between plasma renin activity and distal sodium delivery and reabsorption. Only with the lithium clearance method, however, was it possible to measure plasma renin activity, distal sodium delivery and reabsorption in hydropenia without disturbances of water and electrolyte balance and plasma renin activity level. In hydropenia the plasma renin activity was higher and the fractional distal sodium delivery and reabsorption lower than during volume expansion. Our results support the idea that sodium chloride reabsorption at the macula densa region is negatively correlated to the plasma renin activity in man.

Absorption

Hemodynamic effects of nifedipine in hypertension in the presence of elevated angiotensin-II and beta-adrenergic blockade.

The hemodynamic effects of the slow release form of a calcium channel blocker, nifedipine retard, in essential hypertension patients after angiotensin II (AII) infusion were studied using nuclear ventriculography. Sublingual nifedipine lowered blood pressure that had been acutely raised by an infusion of AII to its baseline level. When used for 4 weeks, nifedipine retard maintained its blood-pressure-lowering effects without a change in heart rate, both when used alone and when used in addition to beta-adrenergic blockers. In the patients with untreated essential hypertension, nifedipine counteracted the lowering effect of AII on left ventricular ejection fraction (LVEF), which was 67.5 +/- 8.9% at recumbency, 61.2 +/- 6.6% (+/- SD) during AII infusion, and 72.1 +/- 7.5% 30 minutes after sublingual nifedipine. These acute effects seem to result from a marked reduction in total peripheral resistance (TPR) and are accompanied by a rise in cardiac index (CI). The TPR, in dynes/sec/cm-5, was 1376.9 +/- 275.8 at recumbency, 2000.7 +/- 358 during AII infusion, and 1228.6 +/- 289 30 minutes after sublingual nifedipine. The corresponding figures for CI in liters/M2 BSA, were 4.02 +/- 0.77, 3.03 +/- 0.64, and 4.32 +/- 0.79. In patients receiving beta-blocker therapy (propranolol or atenolol) with inadequate control of blood pressure, similar results were obtained in LVEF (69.7 +/- 8.87% at recumbency, 63.7 +/- 11.9% during AII infusion, and 72.2 +/- 6.05% 30 minutes after sublingual nifedipine). The initial TPR was much higher than that of untreated essential hypertensive patients. Nevertheless, the increase obtained during AII infusion was counteracted by sublingual nifedipine. CI was decreased by AII.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists

Calcium entry-blockade with verapamil in cyclosporine A plus ischemia induced acute renal failure in rats.

The possible alleviating effect of verapamil, a calcium entry blocker, on the resulting renal damage from the combination of a short episode of ischemia and CyA was studied in rats. Immediately after right nephrectomy the rats were divided into five experimental groups. Group 1: left renal pedicle clamping for 20 minutes. Group 2: as group 1 plus CyA 60 mg/kg bw i.p. Group 3: CyA as in group 2 but sham operated. Group 4: as group 2 plus verapamil 10 mg% in the drinking water. Group 5: as group 3 plus verapamil given as in group 4. The experiments lasted 4 days. By analysis of variance: CyA + ischemia (group 2) showed lower creatinine clearance (p less than 0.001), higher blood urea (p less than 0.01), fractional excretion of sodium (p less than 0.05) and fractional excretion of potassium (p less than 0.01) and fractional excretion of negative free water clearance (p less than 0.001) compared to ischemia alone (group 1). The CyA + ischemia rats treated with verapamil had higher creatinine clearance (p less than 0.05), lower blood urea (p less than 0.01), fractional excretion of sodium (p less than 0.001), fractional excretion of potassium (p less than 0.001) and fractional excretion of negative free water clearance (p less than 0.05) compared with the untreated verapamil CyA + ischemia group. The CyA + sham operated verapamil treated group had similar creatinine clearance with the corresponding verapamil untreated group. The CyA + ischemia group had the higher mean daily body weight reduction compared with all other groups. Histology showed more vacuolization of tubular epithelial cells in the CyA + ischemia than in ischemia alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury

Beta-adrenergic receptors on polymorphonuclear cell membranes in essential hypertension.

Beta adrenergic receptor binding sites were determined and characterized by specific binding of (+/-)[125I] iodocyanopindolol to membranes obtained from circulating polymorphonuclear leukocytes. No difference was found in the number of receptor sites and in their dissociation constants (Kd) between patients with untreated essential hypertension (EH), EH treated with drugs other than beta blockers, and in normotensive controls. The group with EH receiving treatment with beta blockers had a significantly higher receptor density and Kd as compared with all the other groups (p less than 0.05). It is concluded that the beta-adrenergic system of patients with essential hypertension at the receptor level is not different from normotensive subjects and responds to beta blockers by up-regulation.

Adult

Cyclosporine and short ischaemia: a new model of experimental acute renal failure in rats.

To determine whether a mild episode of ischaemia may be a factor in the production of cyclosporine (Cys) toxicity, right nephrectomy was performed in three groups of Charles River rats: I. Ischaemia (left renal pedicle clamping) for 20 minutes, without treatment; II. Ischaemia of 20 minutes, followed by IP Cys 60 mg/kg BW/day; III. Sham (no ischaemia) followed by Cys as in Group II. The rats were sacrificed after four days. Cys plus ischaemia produced a lower creatinine clearance (136 +/- 15 microliter/min/100g BW, p less than 0.001) and a higher FENa per cent (0.94 +/- 0.14, p less than 0.05), FEK (1.07 +/- 0.02, p less than 0.01) compared with ischaemia alone creatinine clearance 261 +/- 39, FENa per cent 0.61 +/- 0.08, FEK 0.54 +/- 0.08, FEH2O -0.04 +/- 0.005. Histology showed more vacuolisation of tubular epithelial cells in the Cys plus ischaemia group than in the ischaemia alone group.

Acute Kidney Injury