Renal function in primary aldosteronism.
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Humans↗
Biomedical subjects
Cristiana Catena
Publications and source records attributed to Cristiana Catena.
Insulin sensitivity in patients with primary aldosteronism: a follow-up study.
CONTEXT: The relationship between aldosterone and glucose metabolism is poorly understood, and there is substantial disparity among findings of studies that have examined glucose tolerance and insulin sensitivity in patients with primary aldosteronism. OBJECTIVE: The objective of the study was to determine the outcome of glucose tolerance and insulin sensitivity in patients with primary aldosteronism after treatment. DESIGN: This was a prospective study of patients who received a diagnosis of primary aldosteronism and were followed up for an average period of 5.7 yr (range, 3-9 yr). SETTING: The study was conducted at a university referral center. PATIENTS: A consecutive sample of 47 patients with tumoral or idiopathic aldosteronism was followed up after either surgical or medical treatment. Patients with primary aldosteronism were compared with 247 patients with essential hypertension with the same severity and duration of disease and 102 normotensive subjects. MAIN OUTCOME MEASURES: Short- and long-term changes in glucose tolerance and insulin sensitivity were measured. RESULTS: After adjustment for age, gender, and body mass index, patients with primary aldosteronism had greater homeostasis model assessment index (P < 0.05) and plasma insulin response to an oral glucose load (P < 0.05) and lower quantitative insulin sensitivity check index (P < 0.01) than normotensive controls. Changes in insulin sensitivity were significantly greater in essential hypertension than primary aldosteronism, and this difference was confirmed by assessment with the hyperinsulinemic-euglycemic clamp (P < 0.01). Treatment of primary aldosteronism decreased blood pressure significantly, and during the initial 6 months of follow-up, parameters of insulin sensitivity were restored to normal. Analysis of subsequent follow-up showed nonsignificant changes in glucose metabolism parameters in both adrenalectomized and spironolactone-treated patients. CONCLUSIONS: Insulin resistance is present in patients with tumoral and idiopathic aldosteronism, but the defect appears less severe than in patients with essential hypertension. Treatment with surgery or aldosterone antagonists restores rapidly and persistently normal sensitivity to insulin.
Aldosterone↗
Long-term renal outcomes in patients with primary aldosteronism.
CONTEXT: Experimental animal studies indicate that exposure to increased aldosterone levels might result in renal damage, but the clinical evidence supporting this role of aldosterone is preliminary. OBJECTIVE: To determine the long-term outcome of renal function in patients with primary aldosteronism after surgical or medical treatment. DESIGN, SETTING, AND PARTICIPANTS: Prospective study conducted at an Italian university medical center among a consecutive sample of 50 patients who were diagnosed as having primary aldosteronism between January 1994 and December 2001 and who were followed up for a mean of 6.4 years after treatment with adrenalectomy or spironolactone. Patients with primary aldosteronism were compared with 100 patients with essential hypertension, matched for severity and duration of hypertension. All patients were treated with antihypertensive drugs to reach a target blood pressure of less than 140/90 mm Hg. MAIN OUTCOME MEASURES: Primary outcome measures were rates of change of glomerular filtration rate and albuminuria during follow-up. Detection of new-onset microalbuminuria and restoration of normal albumin excretion during follow-up were considered as secondary outcomes. RESULTS: At baseline, glomerular filtration rate and albuminuria were higher in patients with primary aldosteronism than those with essential hypertension. The mean blood pressure during the study was 136/81 mm Hg in the primary aldosteronism group and 137/81 mm Hg in the essential hypertension group. Glomerular filtration rate and albuminuria declined during the initial 6-month period in both groups, with a change that was significantly greater (P<.001 for both variables) in patients with primary aldosteronism. Subsequent rate of decline of glomerular filtration was comparable in the 2 groups, whereas albuminuria did not progress in the remainder of the follow-up. Restoration of normal albumin excretion from microalbuminuria was significantly more frequent in primary aldosteronism than in essential hypertension (P = .02). CONCLUSION: In the majority of patients in this study, primary aldosteronism was characterized by partially reversible renal dysfunction in which elevated albuminuria is a marker of a dynamic rather than structural renal defect.
Adrenalectomy↗
Glucose metabolism in early renal failure.
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Creatinine↗
Alcohol-induced endothelial changes are associated with oxidative stress and are rapidly reversed after withdrawal.
BACKGROUND: Although heavy alcohol drinkers are at an increased risk of developing cardiovascular events, moderate alcohol intake is associated with reduced incidence of cardiovascular death. This paradox might reflect a dose-related effect of different alcohol intakes on endothelial function and this, in turn, might depend on changes in oxidative stress. METHODS: We tested the effects of alcohol withdrawal in heavy alcohol consumers and compared the plasma levels of endothelin-1, nitric oxide, plasminogen activator inhibitor-1, von Willebrand factor, malondialdehyde, and intracellular glutathione with those of alcoholics that did not modify their alcohol intake and teetotalers. In human endothelial cells that had been cultured for 2 weeks in the presence of different concentrations of ethanol, we assessed the same parameters after withdrawal of ethanol exposure. RESULTS: Alcohol increased the levels of endothelin-1, nitric oxide, and plasminogen activator inhibitor-1 and decreased the levels of von Willebrand factor both in vivo and in vitro. These changes were dose dependent, rapidly reversed after withdrawal of exposure, and associated with the presence of increased oxidative stress as indicated by increased levels of both malondialdehyde and intracellular glutathione. Blockade of oxidative stress by incubation of endothelial cells in the presence of oxidants' scavengers prevented the alcohol-induced functional modifications of the endothelium. CONCLUSIONS: Alcohol affects endothelial function with an effect that is mediated by an activated oxidative stress and is rapidly reversed after withdrawal. Dose-related endothelial responses to different alcohol intakes might translate in either vascular protection or vascular damage.
Adult↗
New risk factors for atherosclerosis in hypertension: focus on the prothrombotic state and lipoprotein(a).
Although adequate control of blood pressure is of basic importance in cardiovascular prevention in hypertensive patients, correction of additional risk factors is an integral part of their management. In addition to classical risk factors, epidemiological research has identified a number of other conditions that might significantly contribute to cardiovascular risk in the general population and might achieve specific relevance in patients with high blood pressure. In fact, more than 20% of patients with premature cardiovascular events do not have any of the traditional risk factors and, although effective intervention on blood pressure and additional risk factors has significantly reduced cardiovascular morbidity and mortality, the contribution to stroke, coronary artery disease and renal failure is still unacceptably high. Evaluation of new risk factors may further expand our capacity to predict atherothrombotic events when these factors are included along with the traditional ones in the assessment of global cardiovascular risk in hypertensive patients. Because it could be anticipated that the role of these novel factors will become increasingly evident in the future, researchers with an interest in hypertension and physicians dealing with problems related to cardiovascular prevention should give them appropriate consideration. This review summarizes the basic biology and clinical evidence of two emerging risk factors that are reciprocally related and contribute to the development and progression of organ damage in hypertension: the prothrombotic state and lipoprotein(a).
Animals↗
Regression of microalbuminuria in type 1 diabetes.
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Albuminuria↗
Cellular mechanisms of insulin resistance in rats with fructose-induced hypertension.
BACKGROUND: Feeding a high-fructose diet induces hypertension and insulin-resistance in Sprague-Dawley rats. METHODS: To investigate whether insulin receptors contribute to abnormal glucose metabolism and whether their regulation is differentially regulated in different tissues, we evaluated the glycemic and insulinemic response to an oral glucose load, insulin receptor binding, and insulin receptor messengerRNA (mRNA) levels in tissues of rats that were fed either standard rat chow or a diet containing 66% fructose for 2 weeks. RESULTS: Blood pressure and plasma triglycerides increased significantly in the fructose-fed rats, whereas body weight, fasting plasma glucose, and plasma insulin did not differ significantly from controls. Plasma glucose and insulin responses to oral glucose were significantly greater in fructose-fed than in control rats. Insulin receptor-binding characteristics were determined by an in situ autoradiographic technique associated with computerized microdensitometry. The insulin receptor number was significantly lower in both skeletal muscle and liver of fructose-fed rats as compared to controls, whereas no difference was observed in the kidney. No significant differences were found in binding affinity. Insulin receptor mRNA levels were determined by slot-blot hybridization with a cRNA probe encoding the 5' end of the rat insulin receptor cDNA. Consistent with binding data, mRNA levels were significantly lower in skeletal muscle and liver of fructose-fed rats as compared to controls, but not in the kidney. CONCLUSIONS: Decreased number of insulin receptors occurring at the level of gene expression is present in skeletal muscle and liver of fructose-fed rats and might contribute to insulin resistance in this model.
Animals↗
Insulin receptors and renal sodium handling in hypertensive fructose-fed rats.
BACKGROUND: Insulin resistance and hypertension are present in Sprague-Dawley rats fed a fructose-enriched diet. In these rats, insulin might elevate blood pressure via an antinatriuretic action. METHODS: To investigate the sodium-insulin interaction in fructose-fed rats, we compared insulin sensitivity, insulin receptor binding, and insulin receptor mRNA levels in the kidney and skeletal muscle of rats that were fed standard rat chow or a fructose-enriched diet (66%) with either low (0.07%), normal (0.3%), or high (7.5%) NaCl concentrations for 3 weeks. RESULTS: Systolic blood pressure increased in the fructose-fed rats receiving the normal and high-salt diet, but not the low-salt diet. When the rats were fed the low-salt diet, the rate of glucose infusion required to maintain euglycemia during a hyperinsulinemic clamp and insulin receptor number and mRNA levels in skeletal muscle were lower in fructose-fed than control rats. High-salt diet decreased significantly the rate of glucose disposal during the clamp and muscular insulin receptor number and mRNA levels in control, but not fructose-fed rats. During the low-salt diet, renal insulin receptor number and mRNA levels were comparable in fructose-fed and control rats and hyperinsulinemia had comparable acute antinatriuretic effects in the two groups; when the rats were maintained on the high-salt diet, the expected decrease in renal insulin receptor number and mRNA levels occurred in control but not fructose-fed rats and, consistent with this finding, the antinatriuretic response to hyperinsulinemia was blunted only in controls. An inverse relationship between dietary NaCl content and renal insulin receptor mRNA levels was observed in control but not fructose-fed rats. CONCLUSION: Fructose-fed rats appear to have lost the feedback mechanism that limits insulin-induced sodium retention through a down-regulation of the renal insulin receptor when the dietary NaCl content is increased. This abnormality might possibly contribute to the elevation of blood pressure in these rats.
Animals↗
Serum lipoprotein(a) concentrations and alcohol consumption in hypertension: possible relevance for cardiovascular damage.
OBJECTIVES: To evaluate the relationships between alcohol intake and serum lipoprotein(a) [Lp(a)], a powerful predictor of organ damage, in patients with essential hypertension with a wide range of alcohol intake, and to investigate whether the association between alcohol intake and serum Lp(a) concentrations occurs over the entire spectrum of apo(a) phenotypes. DESIGN: Cross-sectional study of a case series. SETTING: University medical centre. PATIENTS: Four hundred and two patients with untreated essential hypertension recruited at a hypertension clinic. MAIN OUTCOME MEASURES: Serum Lp(a) concentrations, apo(a) isoforms, alcohol consumption, smoking habits and cardiovascular status. RESULTS: No difference in Lp(a) concentrations was observed between teetotalers and occasional drinkers. Light drinkers (1-20 g/day ethanol), moderate drinkers (21-50 g/day), and heavy drinkers (> 50 g/day) had, respectively, 21, 26 and 57% lower median Lp(a) concentrations than teetotalers and occasional drinkers. Similar findings were obtained when male and female patients were analysed separately. Log Lp(a) concentrations were inversely and independently correlated with alcohol consumption in both men and women with hypertension. The frequency distributions of apo(a) isoforms and liver function parameters were comparable across the different alcohol intake groups. Patients with evidence of cardiovascular damage had greater concentrations of serum Lp(a) and higher frequency of low-molecular weight apo(a) isoforms as compared with patients without such evidence. CONCLUSIONS: Serum Lp(a) is inversely and dose-dependently related with alcohol intake in patients with hypertension, and this relationship is independent of the size distribution of apo(a) isoforms. Reduction of Lp(a) concentrations by regular consumption of alcohol might favourably affect the atherosclerotic risk profile of patients with hypertension and thereby decrease cardiovascular morbidity.
Adult↗
Abnormalities of glucose metabolism in patients with early renal failure.
Abnormalities of glucose metabolism and hyperinsulinemia have been demonstrated in patients with end-stage renal disease and may contribute to the development of atherosclerotic complications in these patients. In the present study, we investigated the stage of renal failure in which abnormalities of glucose metabolism develop and whether these abnormalities were associated with an increased prevalence of cardiovascular events in patients with early renal failure. In 321 untreated essential hypertensive patients, we assessed renal function by measuring 24-h creatinine clearance, urinary protein excretion, and microalbuminuria; we assessed cardiovascular status by clinical and laboratory tests; and we measured plasma glucose, insulin, and C-peptide levels at fasting and after a 75-g oral glucose load. To evaluate insulin sensitivity, a hyperinsulinemic-euglycemic clamp was performed in a subgroup of 104 patients. Patients with creatinine clearance < 30 ml.min(-1).1.73 m(-2), severe hypertension, BMI < 30 kg/m(2), and diabetes or family history of diabetes were excluded. Hypertensive patients were found to be hyperinsulinemic when compared with 92 matched normotensive subjects. Early renal failure (creatinine clearance < 90 ml.min(-1).1.73 m(-2)) caused by hypertensive nephrosclerosis was detected in 116 of 321 patients. Analysis of patients with varying degrees of renal function impairment demonstrated increased plasma glucose and insulin response to oral glucose load, decreased fasting glucose-to-insulin ratio, and reduced sensitivity to insulin only in those patients with creatinine clearance < 50 ml.min(-1).1.73 m(-2). Parameters of glucose metabolism were not correlated with creatinine clearance and microalbuminuria. Prevalence of atherosclerotic cardiovascular events was significantly related to reduction of creatinine clearance, but parameters of glucose metabolism were comparable in patients with and without evidence of atherosclerotic damage. Thus, in patients with hypertensive nephrosclerosis and early impairment of glomerular filtration, alterations of glucose metabolism become evident only when creatinine clearance is < 50 ml.min(-1).1.73 m(-2) and are not related to microalbuminuria and cardiovascular complications.
Albuminuria↗