Long-term effects of spironolactone on proteinuria and kidney function in patients with chronic kidney disease.

Experimental evidence suggests that aldosterone contributes to progressive kidney disease. Angiotensin-converting enzyme inhibitors and angiotensin type 1 receptor antagonists suppress the renin-angiotensin system but they do not effectively reduce plasma aldosterone. Hence, administration of aldosterone receptor antagonists may provide additional renal protection. In the present prospective randomized open-label study, we evaluated the effects of spironolactone (25 mg/day for 1 year) on proteinuria and estimated glomerular filtration rate in 83 patients with chronic kidney disease already treated with angiotensin-converting enzyme inhibitors and/or angiotensin type 1 receptor antagonists. Eighty-two patients were treated with angiotensin-converting enzyme inhibitors and/or angiotensin type 1 receptor antagonists alone and served as controls. After 1 year of therapy, proteinuria decreased from 2.1+/-0.08 to 0.89+/-0.06 g/g creatinine (P<0.001) in patients treated with spironolactone, but it did not change in control patients. Baseline aldosterone levels were significantly correlated with proteinuria (r=0.76, P<0.0001), and predicted the degree of reduction in proteinuria with spironolactone (r=0.42, P<0.0002). Baseline estimated glomerular filtration rate was similar in patients treated with spironolactone and controls (62.4+/-2.4 and 62.2+/-2.1 ml/min/1.73 m(2), respectively). After 1 month of therapy with spironolactone, estimated glomerular filtration rate decreased more in patients treated with spironolactone than in controls. However, by the end of 1 year the monthly rate of decrease in estimated glomerular filtration rate from baseline was lower in patients treated with spironolactone than in controls (0.323+/-0.044 vs 0.474+/-0.037 ml/min/1.73 m(2), P<0.01). Spironolactone caused a significant rise in serum potassium levels (from 4.2+/-0.04 at baseline to 5.0+/-0.05 mEq/l after 12 months of treatment, P<0.001). In conclusion, this study has shown that spironolactone may reduce proteinuria and retard renal progression in chronic kidney disease patients.

Silent ischemia is more prevalent among hypertensive patients with microalbuminuria and salt sensitivity.

Some patients with essential hypertension manifest greater than normal urinary albumin excretion (UAE). Salt-sensitive hypertensives also manifest greater UAE compared to salt-resistant individuals. Although the significance of these associations is not well established, several lines of evidence suggest that microalbuminuria and/or salt sensitivity may be associated with greater prevalence of cardiovascular risks and events. In this study, we have evaluated by ergometric exercise 42 subjects with microalbuminuria and 42 matched individuals with normal UAE. All these subjects also underwent a standardized protocol to determine blood pressure sensitivity to a high salt intake. Patients with microalbuminuria displayed greater levels of ambulatory blood pressure and a greater rise in systolic blood pressure during exercise compared to patients with normal UAE (33.1 +/- 1.56 vs 26.4 +/- 1.7 mmHg, P < 0.001). Seven hypertensive patients with microalbuminuria developed ST segment depression during exercise compared to only one subject with normal UAE. Salt-sensitive patients manifested greater UAE than salt-resistant subjects (58 and 14 mg, 24 h, P < 0.001) and greater prevalence of silent ischemia (6 vs 2) than salt-resistant individuals. In conclusion, these studies have shown that hypertensive individuals with microalbuminuria and/or salt sensitivity manifest an increased prevalence of silent ischemia.

Social "status" and biological "status": a comparison of grave goods and skeletal indicators from Pontecagnano.

Comparison of funerary treatment and skeletal biology can be very informative about the interplay of social status and meanings and actual life conditions in ancient communities, but such comparison is rarely done, due in part to the disciplinary separation of bioanthropology and social archaeology in many archaeological traditions. In this paper, we analyze relations between skeletal pathologies and grave goods in a sample of 94 individuals from Pontecagnano (Salerno, Italy, seventh-third centuries BC). The results show that the relationship between health, activity, and social status as expressed in grave goods was complex. Some biological indicators considered typical of "stress" or biological status (enamel hypoplasia, cribra orbitalia, adult stature) bore no relation to social status. Other indicators, particularly those of activity and stress in adult life (trauma, Schmorl's nodes, periostitis), covaried with grave assemblage and help to outline a possible division of labor. As this analysis shows, when skeletal and archaeological data are used in conjunction, the result is a deeper picture of the social and economic life of the community than can be obtained from either source.

Microalbuminuria in essential hypertension: significance, pathophysiology, and therapeutic implications.

Some patients with essential hypertension manifest greater than normal urinary albumin excretion (UAE). The significance of this association, which is the object of this review, is not well established. Hypertensive patients with microalbuminuria manifest greater levels of blood pressure, particularly at night, and higher serum levels of cholesterol, triglycerides, and uric acid than patients with normal UAE. Levels of high-density lipoprotein cholesterol, on the other hand, were lower in patients with microalbuminuria than in those with normal UAE. Patients with microalbuminuria manifested greater incidence of insulin resistance and thicker carotid arteries than patients with normal UAE. After a follow-up of 7 years, we observed that 12 cardiovascular events occurred among 54 (21.3%) patients with microalbuminuria and only two such events among 87 patients with normal UAE (P < 0.0002). Stepwise logistic regression analysis showed that UAE, cholesterol level, and diastolic blood pressure were independent predictors of the cardiovascular outcome. Rate of creatinine clearance from patients with microalbuminuria decreased more than that from those with normal UAE. In conclusion, these studies suggest that hypertensive individuals with microalbuminuria manifest a variety of biochemical and hormonal derangements with pathogenic potential, which results in hypertensive patients having a greater incidence of cardiovascular events and a greater decline in renal function than patients with normal UAE.

Association between hyperlipidemia and microalbuminuria in essential hypertension.

BACKGROUND: Some patients with essential hypertension manifest greater than normal urinary albumin excretion (UAE). A few retrospective studies have suggested that there is an association between microalbuminuria and cardiovascular risk. The reasons for this association are not well established, and they are the object of this review. RESULTS: We found that hypertensive patients with microalbuminuria manifest greater levels of blood pressure, particularly at night. Serum levels of cholesterol, triglycerides, and uric acid in patients with microalbuminuria were higher than levels in those with normal UAE, whereas levels of high-density lipoprotein cholesterol in patients with microalbuminuria were lower than levels in patients with normal UAE. Patients with microalbuminuria manifest a greater incidence of insulin resistance, and thicker carotid arteries. After a follow-up of seven years we observed that 12 cardiovascular events occurred among 54 (21.3%) patients with microalbuminuria, and only two such events among 87 patients with normal UAE (P < 0.0002). Stepwise logistical regression analysis showed that UAE, cholesterol level and diastolic blood pressure were independent predictors of the cardiovascular outcome. The rate of clearance of creatinine from patients with microalbuminuria decreased more than did that from those with normal urinary albumin excretion. CONCLUSIONS: These studies suggest that hypertensive individuals with microalbuminuria manifest a variety of biochemical and hormonal derangements with pathogenic potential, which result in greater incidence of cardiovascular events and a greater decline in renal function than do patients with normal UAE.

Microalbuminuria predicts cardiovascular events and renal insufficiency in patients with essential hypertension.

BACKGROUND: Some patients with essential hypertension manifest greater than normal urinary excretion of albumin (UAE). Authors of a few retrospective studies have suggested that there is an association between microalbuminuria and cardiovascular risk. OBJECTIVE: To evaluate whether microalbuminuria is associated with a greater than normal risk of cardiovascular and renal events. METHODS: We performed a retrospective cohort analysis of 141 hypertensive individuals followed up for approximately 7 years. Hypertensive patients were defined as having microalbuminuria if the baseline average UAE of three urine collections was in the range 30-300 mg/24 h. RESULTS: Fifty-four patients had microalbuminuria and 87 had normal UAE. At baseline, the two groups were similar for age, weight, blood pressure, and rate of clearance of creatinine. Serum levels of cholesterol, triglycerides, and uric acid in patients with microalbuminuria were higher than levels in those with normal UAE, whereas levels of high-density lipoprotein cholesterol in patients with microalbuminuria were lower than levels in patient with normal UAE. During follow-up, 12 cardiovascular events occurred among the 54 (21.3%) patients with microalbuminuria and only two such events among the 87 patients with normal UAE (P < 0.0002). Stepwise logistic regression analysis showed that UAE (P = 0.003), cholesterol level (P = 0.047) and diastolic blood pressure (P = 0.03) were independent predictors of the cardiovascular outcome. Rate of clearance of creatinine from patients with microalbuminuria decreased more than did that from those with normal UAE (decrease of 12.1 +/- 2.77 versus 7.1 +/- 0.88 ml/min, P < 0.03). CONCLUSIONS: This study suggests that hypertensive individuals with microalbuminuria manifest a greater incidence of cardiovascular events and a greater decline in renal function than do patients with normal UAE.

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.

Microalbuminuria in essential hypertension.

Some patients with essential hypertension manifest increased urinary albumin excretion (UAE). Hypertensive patients with microalbuminuria manifest abnormal circadian variation of blood pressure, increased serum levels of LDL-cholesterol and lipoprotein(a), a greater rise of serum insulin in response to an oral glucose tolerance test, and greater thickness of the carotid artery than patients without microalbuminuria. A 7 year follow-up of 141 hypertensive patients, 54 with microalbuminuria and 87 without microalbuminuria, we observed 12 cardiovascular events in patients with microalbuminuria and only 2 events in the patients with normal urine albumin excretion (P < 0.0002). Creatinine clearance decreased more in patients with microalbuminuria than in those with normal UAE. In conclusion, hypertensive individuals with microalbuminuria manifest a greater incidence of cardiovascular events and more decline in renal function than patients with normal UAE. We propose that measurements of UAE may be a useful marker for cardiovascular risk in patients with essential hypertension.

Hyperinsulinemia, circadian variation of blood pressure and end-organ damage in hypertension.

BACKGROUND: Some patients with essential hypertension display hyperinsulinemia and/or insulin resistance. A relationship between hyperinsulinemia and blood pressure has not been conclusively established. Some evidence points to a relationship between hyperinsulinemia and evidence of cardiovascular damage. OBJECTIVES: In this study, we examined the relationship between insulin secretion in response to an oral glucose load, circadian variation of blood pressure, and evidence of vascular damage, measured by the thickness of the carotid artery and urinary albumin excretion. DESIGN: Seventy patients with essential hypertension and 35 healthy volunteers were included in the study. RESULTS: Twenty patients were hyperinsulinemic. Office blood pressure was not different between hypertensive patients with high and those with normal insulin AUC. However, night-time diastolic blood pressure was greater in hypertensive patients with high insulin AUC (93 +/- 2.9 mm Hg) than in those with normal insulin AUC (83.5 +/- 1.7 mm Hg, P < 0.005). The thickness of the carotid artery and urinary albumin excretion were greater (P < 0.05) in patients with high insulin AUC than in patients with normal insulin AUC and normotensive subjects. Insulin AUC was significantly correlated with ambulatory blood pressure, carotid artery thickness, and urine albumin excretion. Multiple regression analysis using insulin AUC as the dependent variable and UAE, triglycerides, body-mass index and office or ambulatory blood pressure as independent variables showed the strongest correlation with urine albumin excretion (P < 0.0001), triglycerides (P < 0.02) and body-mass index (P < 0.07). CONCLUSIONS: These data suggest that in patients with essential hypertension hyperinsulinemia is associated with higher levels of nocturnal blood pressure, and greater evidence of vascular damage.

Altered circadian blood pressure profile and renal damage.

Introduction. The relationship between arterial hypertension and renal damage has long been recognized. In 1836, Bright reported an association between cardiac hypertrophy and contraction of the kidney [1] and 40 years later Gull and Sutton [2] suggested that the renal damage in patients with arterial hypertension could be the consequence of vascular hypertensive alterations.

Salt intake and plasma atrial natriuretic peptide and nitric oxide in hypertension.

In response to a high salt intake, salt-sensitive hypertensive individuals retain more sodium and manifest a rise in blood pressure greater than that in salt-resistant individuals. In this study, we tested whether salt sensitivity might be related at least in part to reduced secretion of atrial natriuretic peptide (ANP) or to abnormal nitric oxide production. We measured plasma ANP and NO2+NO3 in 7 normotensive individuals and 13 salt-sensitive and 14 salt-resistant blacks with essential hypertension under conditions of low (10 mEq/d) and high (250 mEq/d) salt intake. To evaluate possible racial differences in ANP secretion, we also measured plasma ANP in 6 salt-sensitive and 8 salt-resistant hypertensive whites during low and high salt intakes. Under low salt conditions, plasma ANP levels were not different in normotensive control subjects and salt-sensitive and salt-resistant hypertensive blacks. During high salt intake, plasma ANP levels did not change in control subjects and salt-resistant patients but decreased in salt-sensitive patients. ANP levels after high salt diet were lower (P < .01) in salt-sensitive than salt-resistant blacks. In hypertensive whites, high salt intake caused no significant change in plasma ANP. Under low salt conditions, plasma NO2+NO3 levels were higher (P < .05) in salt-sensitive (189 +/- 7.9 mumol/L) and salt-resistant (195 +/- 13.5 mumol/L) black patients than in control subjects (108 +/- 9.7 mumol/L). During high salt intake, plasma NO2+NO3 decreased significantly (P < .01) in both salt-sensitive (150 +/- 7.0 mumol/L) and salt-resistant (142 +/- 9.0 mumol/L) patients. These studies show that under conditions of high salt intake, salt-sensitive hypertensive blacks manifest a paradoxical decrease in ANP secretion. This abnormality may play a role in the reduced ability of these individuals to excrete a sodium load and in the sodium-induced rise in blood pressure. This study does not support the hypothesis that salt sensitivity depends on a deficit of nitric oxide production, but it suggests that high salt intake may alter the endothelium-dependent adaptation of peripheral resistance vessels.

Effect of insulin on renal sodium and uric acid handling in essential hypertension.

In normal subjects, insulin decreases the urinary excretion of sodium, potassium, and uric acid. We tested whether these renal effects of insulin are altered in insulin resistant hypertension. In 37 patients with essential hypertension, we measured the changes in urinary excretion of sodium, potassium, and uric acid in response to physiological euglycemic hyperinsulinemia (by using the insulin clamp technique at an insulin infusion rate of 6 pmol/min/kg). Glucose disposal rate averaged 26.6 +/- 1.5 mumol/min/kg, i.e., 20% lower than in normotensive controls (33.1 +/- 2.1 mumol/min/kg, P = .015) In the basal state, fasting plasma uric acid concentrations were higher in men than women (P < .001), were positively related to body mass index (r = 0.38, P = .02), waist/hip ratio (r = 0.35, P < .05), and serum triglyceride levels (r = 0.59, P = .0001), and negatively related to HDL cholesterol concentrations (r = -0.59, P = .0001) and glucose disposal rate (r = 0.42, P < .01). Uric acid clearance, on the other hand, was inversely related to body mass index (r = 0.41, P = .01), plasma uric acid (r = 0.65, P < .0001) and triglyceride concentrations (r = 0.39, P < .02), and directly related to HDL cholesterol levels (r = 0.52, P < .001). During insulin infusion, blood pressure, plasma uric acid and sodium concentration, and creatinine clearance did not change. In contrast, hyperinsulinemia caused a significant decrease in the urinary excretion of uric acid (2.67 +/- 0.12 to 1.86 +/- .14 mumol/min/1.73 m2, P = .0001), sodium (184 +/- 12 to 137 +/- 14 mumol/min/1.73 m2, P = .0001), and potassium (81 +/- 7 to 48 +/- 4 mumol/ min/1.73 m2, P = .0001). Both in absolute terms (clearance and fractional excretion rates) and percentagewise, these changes were similar to those found in normotensive subjects. Insulin-induced changes in urate excretion were coupled (r = 0.55, P < .0001) to the respective changes in sodium excretion. In hypertensive patients, higher uric acid levels and lower renal urate clearance rates cluster with insulin resistance and dyslipidemia. Despite insulin resistance of glucose metabolism, acute physiological hyperinsulinemia causes normal antinatriuresis, antikaliuresis, and antiuricosuria in these patients.

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)

Altered norepinephrine turnover in the brown fat of rats with chronic renal failure.

Disturbances of the sympathetic nervous system (SNS) have been described in chronic renal failure, but their role in the metabolic derangements of uremia has not been well established. In these studies, SNS activity has been measured in the ventromedial hypothalamic (VMH) nuclei and in the intercostal brown adipose tissue (IBAT) of Sprague Dawley 5/6 nephrectomized or sham-operated rats. SNS activity was determined by calculating the norepinephrine (NE) turnover rate (in picograms per milligram per hour) 3, 6, and 12 h after the inhibition of NE synthesis with L-methyltyrosine. The endogenous NE concentration was significantly (P < 0.01) higher in the VMH (14,567 +/- 1,130 pg/mg wet wt) and IBAT (17,902 +/- 2,308 pg/mg wet wt) of uremic than control rats (9,600 +/- 1,110 and 5,752 +/- 320 pg/mg wet wt, respectively). The turnover rates of NE in the VMH (582 +/- 146 pg/mg per hour) and in the IBAT (1,432 +/- 179 pg/mg/hr) of uremic rats were significantly faster (P < 0.01) than in control rats (192 +/- 96 and 173 +/- 58 pg/mg per hour, respectively). These studies demonstrate a significant increase in NE turnover in the VMH nuclei and IBAT of uremic rats. It is suggested that increased efferent sympathetic nerve discharge from the VMH to the IBAT may play a role in the pathogenesis of malnutrition in uremia.