Bilateral fibromuscular dysplasia in identical twins.

Fibromuscular dysplasia is an arterial occlusive disorder that often affects the renal arteries and leads to renovascular hypertension. The cause of this disease is unknown. However, the occurrence in siblings suggests that genetic factors may play a role. We describe two cases involving hypertensive identical twins with fibromuscular dysplasia of the renal arteries. This unique clinical case reinforces a possible hereditary nature of this arterial occlusive disorder.

Clustering of cardiovascular risk factors in salt-sensitive patients with essential hypertension: role of insulin.

Hyperinsulinemia, insulin resistance, or both have been described in a proportion of patients with essential hypertension, and also are considered a risk for atherosclerotic cardiovascular disease. In this study, we have examined whether salt sensitivity and hyperinsulinemia are associated in patients with essential hypertension. We have measured blood insulin and glucose response to an acute oral glucose load in a group of hypertensive patients, classified according to their salt sensitivity. To determine salt sensitivity, patients received a diet containing a low (20 mEq/day) Na+ intake for 1 week followed by a high (250 mEq/day) Na+ intake for 1 week more. Twenty-nine patients were classified as salt sensitive, and 23 as salt resistant. Baseline plasma glucose and insulin were not different between salt-sensitive and salt-resistant patients. Following an oral glucose load, the area-under-the curve of glucose was greater (P < .05) in salt-sensitive than in salt-resistant hypertensive patients (900 +/- 26.4 and 810 +/- 29.1 mmol/L x 2 h, respectively). The area-under-the curve of insulin was greater (P < .01) in salt-sensitive (52,664 +/- 3,666 pmol/L x 2 h) than in salt-resistant patients (37,977 +/- 3,300 pmol/L x 2 h). A direct correlation was present between insulin area-under-the curve and salt sensitivity (r = 0.26), but did not reach statistical significance (P < .06). Salt-sensitive patients manifested increased serum levels of total cholesterol, LDL-cholesterol and increased urinary albumin excretion when compared with salt-resistant patients. In conclusion, these studies have demonstrated that in response to an oral glucose load, salt-sensitive patients with essential hypertension manifest increased insulin secretion. The studies have confirmed the presence of increased urinary albumin excretion and serum levels of atherogenic lipoproteins in salt-sensitive compared with salt-resistant patients. In salt-sensitive hypertensive patients, hyperinsulinemia, hyperlipidemia and microalbuminuria form a cluster with possible atherogenic potential. Salt sensitivity can be a marker for increased cardiovascular risk in patients with essential hypertension.

Insulin resistance in microalbuminuric hypertension. Sites and mechanisms.

Microalbuminuria in patients with essential hypertension is a marker of incipient glomerular dysfunction and clusters with lipid and hemodynamic abnormalities. Recent evidence has shown that hypertensive patients with microalbuminuria have a hyperinsulinemic response to oral glucose, suggesting the presence of insulin resistance. To directly test this possibility we studied insulin action in two accurately matched groups (n = 10 each) of hypertensive patients with or without microalbuminuria (14 +/- 2 versus 52 +/- 7 mg/24 h-1, mean of three 24-hour collections). In response to glucose ingestion microalbuminuric patients showed slight hyperglycemia (area under the curve, 928 +/- 43 versus 784 +/-19 nmol/L-1/2h-1, P < .02) and a marked hyperinsulinemia (26.8 +/- 3.3 versus 49.8 +/- 3.7 nmol/L-1/2h-1, P < 0.01). Basal arterial blood pressure, heart rate, and forearm blood flow were similar in the two groups and did not change significantly during a 2-hour euglycemic insulin clamp. Insulin-stimulated wholebody glucose uptake was 25% lower in microalbuminuric patients (33.5 +/- 2.5 versus 25.2 +/- 2.1 mumol/min-1/kg-1, P < .02). This difference was entirely due to a 40% reduction in glycogen synthesis (12.9 +/- 1.8 versus 21.3 +/- 3.2 mumol/min-1/kg-1, P < .05) as glucose oxidation was similarly stimulated in the two groups. In contrast there was no difference in the ability of insulin to suppress hepatic glucose production (by approximately 100% at the end of the clamp), to decrease fractional sodium and potassium excretions (by 35%), to lower circulating free fatty acids (by 80%), and to reduce plasma potassium concentrations (by 10%).(ABSTRACT TRUNCATED AT 250 WORDS)

Increased thickness of the carotid artery in patients with essential hypertension and microalbuminuria.

In patients with essential hypertension, the presence of microalbuminuria carries an increased risk for cardiovascular morbidity and mortality. The mechanisms responsible for this association are not clear. Microalbuminuria could signal the presence of generalised atherosclerosis. To determine the extent of atherosclerosis, we measured by B-mode ultrasound imaging the thickness of the intima and media layers of the carotid artery in 30 hypertensive patients with microalbuminuria, 30 patients without microalbuminuria and 30 normotensive healthy subjects. In hypertensive patients with microalbuminuria, urinary albumin excretion (55 +/- 4.7 mg/24 h) was greater (P < 0.01) than in patients without microalbuminuria (12 +/- 0.9 mg/24 h) and in healthy subjects (7.1 +/- 0.52 mg/24 h). In hypertensive patients with microalbuminuria, the thickness of the carotid artery (0.78 +/- 0.02 mm) was greater (P < 0.01) than in patients without microalbuminuria (0.69 +/- 0.01 mm) and in healthy subjects (0.64 +/- 0.02 mm). In hypertensive patients with microalbuminuria, the mean insulin area-under-the curve (59,703 +/- 4,874 pmol/L x 2 h) and glucose area-under-the curve (928 +/- 40.0 mmol/L x 2 h) were significantly greater (P < 0.005) than in patients without microalbuminuria (38,774 +/- 4,104 pmol/L x 2 h and 803 +/- 34.7 mmol/L x 2 h, respectively), and in normotensive healthy subjects (27,557 +/- 2563 pmol/L x 2 h and 837 +/- 31.2 mmol/L x 2 h, respectively). Serum levels of total cholesterol, triglycerides and lipoprotein(a) were higher in hypertensives with than in those without microalbuminuria. The thickness of the carotid artery was significantly correlated with microalbuminuria, blood pressure, cholesterol, serum triglycerides and insulin area-under-the curve. In conclusion, this study shows that hypertensive patients with microalbuminuria have an increased thickness of the carotid intima and media layers suggesting a greater degree of atherosclerosis. Measurements of urinary albumin excretion may be important in the evaluation of patients with essential hypertension.

Elevated serum insulin levels in patients with essential hypertension and microalbuminuria.

Hyperinsulinemia, insulin resistance, or both have been described in patients with essential hypertension. Previous work from our laboratory has shown that in hypertensive patients with microalbuminuria, dyslipidemia and abnormal patterns in the diurnal variations of blood pressure are frequently associated. Whether hyperinsulinemia and microalbuminuria are directly related has not been determined. To test this possibility, we measured the plasma insulin response to an oral glucose load in 25 patients with or without microalbuminuria and 20 normotensive control subjects. Serum lipid profile and 24-hour ambulatory blood pressure were obtained. In the hypertensive patients as a group, the plasma insulin response to glucose (evaluated as the insulin area under the curve) was significantly enhanced compared with a group of 20 normotensive healthy control subjects (46,311 +/- 3745 and 27,557 +/- 2563 pmol/L x 2 hours, P < .01). When the hypertensive patients were subdivided according to their albumin excretion rate, the microalbuminuric patients had significantly higher plasma glucose (969 +/- 45.2 versus 762 +/- 28.7 mmol/L x 2 hours, P < .01) and insulin (59,172 +/- 5964 versus 37,737 +/- 3422 pmol/L x 2 hours, P < .01) area under the curve values. In addition, a significant direct correlation was found to exist between insulin area under the curve and the urinary albumin excretion rate (r = .63, P < .001). Serum levels of lipoprotein(a) were significantly greater (P < .01) in patients with than in those without microalbuminuria and in control subjects. Furthermore, daytime diastolic blood pressure and nighttime systolic and diastolic blood pressure values were greater in patients with than in those without microalbuminuria.(ABSTRACT TRUNCATED AT 250 WORDS)

Microalbuminuria in salt-sensitive patients. A marker for renal and cardiovascular risk factors.

We previously showed that a high salt diet increases glomerular capillary pressure in salt-sensitive hypertensive patients and suggested that this may underlie the greater propensity of these patients to develop renal failure. Because microalbuminuria is considered an initial sign of renal damage, we have tested whether salt-sensitive patients display greater urinary albumin excretion than salt-resistant hypertensive patients. Twenty-two patients were placed on a low sodium intake (20 mEq/d) for 7 days followed by a high sodium diet (250 mEq/d) for 7 more days. Twelve patients were classified as salt sensitive and 10 as salt resistant. Urinary albumin excretion was greater in salt-sensitive than salt-resistant patients (54 +/- 11 versus 22 +/- 5 mg/24 h, P < .01). During the low sodium diet, glomerular filtration rate, renal plasma flow, and filtration fraction were similar between the two groups. During the high sodium intake, glomerular filtration, renal plasma flow, filtration fraction, and calculated intraglomerular pressure did not change in salt-resistant patients; in salt-sensitive patients, however, renal plasma flow decreased, and filtration fraction and intraglomerular pressure increased, whereas glomerular filtration rate did not change. Urinary albumin excretion was significantly correlated with glomerular capillary pressure. Salt-sensitive patients displayed higher serum levels of low-density lipoprotein cholesterol and lipoprotein(a) and lower levels of high-density lipoprotein cholesterol than salt-resistant patients. These studies have shown greater urinary albumin excretion and serum concentrations of atherogenic lipoproteins in salt-sensitive than in salt-resistant hypertensive patients, suggesting that salt sensitivity may be a marker for greater risk of renal and cardiovascular complications.

Diurnal variations of blood pressure and microalbuminuria in essential hypertension.

Microalbuminuria has been shown in approximately 40% of patients with essential hypertension. Previous studies have failed to demonstrate any consistent relationship between microalbuminuria and levels of office blood pressure. Because average ambulatory blood pressure correlates with incidence of cardiovascular morbidity and mortality better than office blood pressure, we have studied whether levels of urinary albumin excretion correlate with average diurnal, nocturnal, or 24-h blood pressure better than with office blood pressure. Sixty-three patients with essential hypertension and 21 healthy volunteers were included in the study. Twenty-four hypertensive patients failed to show the normal nighttime fall in blood pressure of at least 10/5 mm Hg and were defined as "nondippers"; the remaining were defined as "dippers." Office blood pressure was not different between dippers and nondippers. However, nighttime systolic and diastolic blood pressures were significantly greater in nondippers than in dippers. The median urinary albumin excretion in nondippers (42 mg/24 h) was significantly greater (P < .001) than in dippers (17.5 mg/24 h), and in normal subjects (8.6 mg/24 h). A significant correlation was present between nighttime systolic and diastolic blood pressure and urinary albumin excretion (UAE) and between 24-h systolic blood pressure and UAE in all hypertensive patients; in addition, a significant correlation was present between 24-h diastolic and nighttime diastolic blood pressure and UAE in nondippers. The increased amount of UAE in nondipper hypertensive patients suggests the presence of greater renal damage than in dippers.

Long-term effects of a converting enzyme inhibitor and a calcium channel blocker on urinary albumin excretion in patients with essential hypertension.

Microalbuminuria in patients with essential hypertension is associated with increased incidence of cardiovascular morbidity and mortality. Reduction of urinary albumin excretion (UAE) with therapy could reduce cardiovascular events. The long-term effect of commonly used antihypertensive agents on UAE has not been properly investigated. In the present study, we have prospectively studied the effects of therapy for 24 months with a converting enzyme inhibitor, enalapril, or a calcium channel blocker, nicardipine, on UAE in 40 patients with essential hypertension and microalbuminuria. Enalapril and nicardipine were equally effective in reducing arterial pressure. However, enalapril decreased UAE from 77.1 +/- 10.4 to 30.4 +/- 7.9 mg/24 h after 1 year, and to 24.7 +/- 4.8 (P < .01) after 2 years of therapy. UAE however, did not change in patients treated with nicardipine (from 65.2 +/- 12 to 73 +/- 14 after 1 year, and to 52.7 +/- 21 mg/24 h after 2 years of therapy). The impact of reducing UAE on overall cardiovascular morbidity and mortality and on future progression of renal failure in patients with essential hypertension remains to be established.

Microalbuminuria in patients with essential hypertension: effects of several antihypertensive drugs.

PURPOSE: Microalbuminuria can be present in 10% to 40% of patients with essential hypertension and is associated with an increased incidence of cardiovascular events. The effect of commonly used antihypertensive agents on urinary albumin excretion (UAE) has not been well established. The aim of this study was to evaluate the effects of a converting enzyme inhibitor, a calcium channel blocker, a beta blocker, and a diuretic on UAE and on creatinine clearance in patients with mild to moderate hypertension. PATIENTS AND METHODS: We prospectively measured UAE prior to and 4 and 8 weeks after treatment with enalapril, nitrendipine, atenolol, or a diuretic in 48 patients with essential hypertension and microalbuminuria. RESULTS: All these agents were equally effective in reducing arterial pressure. However, enalapril but not the other agents significantly decreased UAE. CONCLUSION: Eight weeks of therapy with enalapril may reduce UAE in patients with mild to moderate essential hypertension, whereas other agents, such as nitrendipine, atenolol, or diuretics, had no measurable effect on UAE. The clinical and prognostic significance of these observations remains to be established.

Prevalence of microalbuminuria in a large population of patients with mild to moderate essential hypertension.

To determine the prevalence of increased urinary albumin excretion (UAE) in essential hypertension and to establish whether this abnormality is associated with deranged renal function, we have measured UAE in a group of 123 patients with essential hypertension and in 110 normal subjects. Mean arterial pressure (MAP) was 96 +/- 0.6 mm Hg in normal subjects and 121 +/- 0.3 mm Hg in patients with essential hypertension (p less than 0.01). Mean UAE was 8.6 +/- 0.5 in normal subjects and 32.9 +/- 3.3 mg/24 h in patients with essential hypertension (p less than 0.01). Forty percent of patients with essential hypertension manifested a UAE exceeding 30 mg/24 h and had an average UAE of 72.0 +/- 4.7 mg/24 h. MAP in patients with increased UAE was similar to that in subjects with normal UAE (121 +/- 0.5 vs. 121 +/- 0.4 mm Hg). Creatinine clearance was also not different between these two groups (91 +/- 1.8 vs. 94 +/- 1.5 ml/min). No correlation was found between UAE and MAP or creatinine clearance. Long-term prospective studies are needed to extablish whether an increase in UAE may predict future nephrosclerosis in essential hypertension.

Microalbuminuria in patients with essential hypertension. Effects of an angiotensin converting enzyme inhibitor and of a calcium channel blocker.

Several patients with essential hypertension manifest an abnormal (greater than 30 mg/24 h) urinary albumin excretion (UAE). Since microalbuminuria is considered an independent predictor of cardiovascular morbidity and mortality, studies are currently being undertaken to determine the effect of various antihypertensive agents on UAE, on the assumption that a reduction of UAE might result in improved prognosis in patients with essential hypertension. Twenty-four patients with essential hypertension were randomly divided into two groups of 12. The first group received 20 mg/day enalapril for 8 weeks, followed by 20 to 40 mg/day nitrendipine for 8 more weeks. The second group received nitrendipine for 8 weeks, followed by enalapril. Mean arterial pressure decreased similarly during both therapeutic regimens in the two groups of patients. In patients of group 1, UAE decreased significantly (P less than .01) from 74 +/- 7.0 to 33 +/- 5.8 mg/24 h after 8 weeks of treatment with enalapril; during the following 8 weeks of treatment with nitrendipine, UAE increased to 58 +/- 5.3 mg/24 h (P less than .02). In patients of group 2, UAE did not change during the first 8 weeks of therapy with nitrendipine despite a significant reduction in blood pressure; subsequently, after 8 weeks of therapy with enalapril, UAE decreased from 62 +/- 9.2 to 31 +/- 4.8 mg/24 h (P less than .01). This study demonstrates that enalapril but not nitrendipine may reduce UAE in patients with essential hypertension despite similar antihypertensive efficacy. The significance of microalbuminuria and the impact of the normalization of UAE on cardiovascular morbidity and mortality in patients with essential hypertension remains to be determined.

Long-term effects of enalapril and nicardipine on urinary albumin excretion in patients with chronic renal insufficiency: a 1-year follow-up.

The long-term effects of converting enzyme inhibitors and calcium channel blockers on proteinuria and the progression of renal disease in patients with hypertension and chronic renal insufficiency are not well established. We have studied the long-term effects of treating hypertension with an angiotensin-converting enzyme inhibitor, enalapril, and a calcium channel blocker, nicardipine, on urinary albumin excretion (UAE) and on renal function in 16 patients with hypertension and chronic renal insufficiency (creatinine clearance ranging between 17 and 62 ml/min). After 1 year of treatment, these agents caused a similar decrease in blood pressure. Only enalapril, however, caused a significant decrease in UAE (from 641 +/- 98 to 292 +/- 47 mg/24 h, p less than 0.01), whereas UAE did not change in the group treated with nicardipine (675 +/- 78 vs. 601 +/- 75 mg/24 h). Creatinine clearance at the beginning of the study was similar in the group treated with enalapril and in the group treated with nicardipine (35 +/- 3.6 vs. 40 +/- 4.1 ml/min). After 1 year of follow-up, creatinine clearance remained unchanged in both groups of patients. These studies demonstrate that both enalapril and nicardipine can effectively reduce blood pressure in patients with hypertension and chronic renal insufficiency. Enalapril but not nicardipine, however, appears to reduce urinary albumin excretion in these patients. Whether the reduction in UAE has any significant impact on the progression of renal disease remains to be established.

High-permeable membranes and hypersensitivity-like reactions: role of dialysis fluid contamination.

We have recently observed repeated hypersensitivity-like reactions (skin flush, face and tongue tingling, hypotension, and dispnea) during the first 5 min of dialysis in a small number of our dialysis population treated with high-flux membranes and traditional acetate dialysate. This prompted us to investigate the relationship between these reactions and the presence of contamination of the dialysate fluid. We hypothesized that in the presence of contaminated dialysate fluid and high-flux membranes backfiltration of pyrogens may occur through the membrane into the blood compartment, leading to hypersensitivity-like reactions. These events are more likely to occur at the onset of dialysis due to rapid changes of hydrostatic pressure gradients across the dialysis membranes. 6 out of 48 dialysis patients who experienced hypersensitivity-like reactions were followed for 4 weeks. During the 1st week they were treated with high-permeable membranes and during the 2nd week with cuprophane membranes. The dialysate showed high levels of contamination with bacteria and endotoxin during dialysis with both types of membranes (microbial count 4,123 +/- 2,756 and 1,991 +/- 1,950 colony-forming units/ml; endotoxin 26.2 +/- 8.4 and 23 +/- 4.2 endotoxin units/ml, respectively); however the symptoms occurred only during dialysis with high-flux membranes. This suggests that backfiltration of contaminated dialysate into the blood might have occurred during the early phases of dialysis only when using high-flux membranes, but not when using cuprophane membranes. To test this possibility we introduced a new dialyzer-rinsing device consisting of two simple connection lines which allow to rinse, in a concurrent manner, the dialysate and the blood compartments of the dialyzer with sterile saline solution.(ABSTRACT TRUNCATED AT 250 WORDS)

Biofiltration, a new method of short hemodiafiltration: preliminary report.

Four patients previously treated by traditional dialysis (HD, 240 min) were switched to biofiltration (BF, 180-210 min) and followed for twelve months. Before and at the end of this period, clinical and biochemical data were assessed for each patient. Patients treated for 180 min by BF presented no increase in BUN but a significant increase of predialytic phosphorus. The 210 min BF schedule achieved the same pattern of depuration as HD. Acidosis was corrected better in all patients during BF. No hypoxemia and no change of WBC count were observed during BF. Cardiac function, assessed by echocardiography, improved similarly with each session of both methods. BF is a useful alternative treatment procedure for patients with endstage renal failure.

Hemodiafiltration (HD-HF): one year follow-up of nine hours weekly.

Data are presented concerning our experience with hemodiafiltration (HD-HF) in uremic patients. Ten patients previously submitted to regular dialysis treatment, cuprophane membrane (RDT), for the last year twelve hours weekly, were treated for one year, nine hours weekly, HD-HF. Five of ten had suffered discomfort by RDT and five spontaneously chose HD-HF owing to its shorter treatment period. The follow-up of the two treatment schedules did not show any significant difference in absolute and percentage values of small molecules. Hematocrit, body weight and blood arterial pressure were not different following both treatment. Patients submitted to HD-HF complained of no discomfort including patients suffering of dialytic discomfort under RDT. HD-HF has proved as useful and more comfortable than RDT in long-term treatment of patients with chronic renal failure.