[Microalbuminuria and urinary albumin excretion: French guidelines]. / Microalbuminurie et excrétion urinaire d'albumine: recommandations pour la pratique clinique.

UNLABELLED: Measurement of urinary albumin excretion (UAE) may be done on a morning urinary sample or on a 24 hour-urine sample. Values defining microalbuminuria are: - 24-hour urine sample: 30-300 mg/24 hours - Morning urine sample: 20-200 mg/mL or 30-300 mg/g creatinine or 2.5-25 mg/mmol creatinine (men) or 3.5-35 mg/mol (women). - Timed urine sample: 20-200 mug/min. The optimal use of semi-quantitative urine test-strip is not clearly defined. It is generally believed that microalbuminuria reflects a generalized impairment of the endothelium; however, no definite proof has been shown in humans. In diabetic subjects, microalbuminuria is a marker of increased risk of cardiovascular (CV) and renal morbidity and mortality in type 1 and type 2 diabetic subjects. The increase in UAE during follow-up is also a marker of CV and renal risk in type 1 and type 2 diabetic subjects; its decrease during follow-up is associated with lower risks. In non-diabetic subjects, microalbuminuria is a marker of increased risk for diabetes mellitus, deterioration of the renal function, CV morbidity and all-cause mortality. It is a marker of increased risk for the development of hypertension in normotensive subjects, and is associated with unfavorable outcome in patients with cancer and lymphoma. Persistence or elevation of UAE overtime is associated with deleterious outcome in some hypertensive subjects. Measurement of UAE may be recommended in hypertensive subjects with 1 or 2 CV risk factors in whom CV risk remains difficult to assess, and in those with refractory hypertension: microalbuminuria indicates a high CV risk and must lead to strict control of arterial pressure. Studies focused on microalbuminuria in non-diabetic, non-hypertensive subjects are limited; most of them suggest that microalbuminuria predicts CV complications and deleterious outcome as it is in diabetic or hypertensive subjects. Subjects with a history of CV or cerebrovascular disease have an even greater CV risk if microalbuminuria is present than if it is not; however, in all cases, therapeutic intervention must be aggressive regardless of whether microalbuminuria is present or not. It is not recommended to measure UAE in non-diabetic non-hypertensive subjects in the absence of history of renal disease. Monitoring of renal function (UAE, serum creatinine and estimation of GFR) is annually recommended in all subjects with microalbuminuria. MANAGEMENT: in patients with microalbuminuria, weight reduction, sodium restriction (< 6 g/day), smoking cessation, strict glucose control in diabetic subjects, strict arterial pressure control are necessary; in diabetic subjects: use of maximal doses of ACEI or ARB are recommended; ACEI/ARB and thiazides have synergistic actions on arterial pressure and reduction of UAE; in non-diabetic subjects, any of the five classes of anti-hypertensive medications (ACEI, ARB, thiazides, calcium channel blockers or beta-blockers) can be used.

Microalbuminuria and urinary albumin excretion: French clinical practice guidelines.

Urinary albumin excretion (UAE) may be assayed on a morning urinary sample or a 24 h-urine sample. Values defining microalbuminuria are: 1) 24-h urine sample: 30-300 mg/24 h; 2) morning urine sample: 20-200 mg/ml or 30-300 mg/g creatinine or 2.5-25 mg/mmol creatinine (men) or 3.5-35 mg/mmol (women); 3) timed urine sample: 20-200 mug/min. The optimal use of semi-quantitative urine test-strip is not clearly defined. It is generally believed that microalbuminuria reflects a generalized impairment of the endothelium; however, no definite proof has been obtained in humans. IN DIABETIC SUBJECTS: Microalbuminuria is a marker of increased risk of cardiovascular (CV) and renal morbidity and mortality in type 1 and type 2 diabetic subjects. The increase in UAE during follow-up is associated with greater CV and renal risks in type 1 and type 2 diabetic subjects; its decrease during follow-up is associated with lower risks. IN NON-DIABETIC SUBJECTS: Microalbuminuria is a marker of increased risk for diabetes mellitus, deterioration of renal function, CV morbidity and all-cause mortality. It is a marker of increased risk for the development of hypertension in normotensive subjects, and is associated with unfavorable outcome in patients with cancer and lymphoma. Persistence of elevated UAE during follow-up is associated with poor outcome in some hypertensive subjects. Measurement of UAE may be recommended in hypertensive medium-risk subjects with 1 or 2 CV risk factors in whom CV risk remains difficult to assess, and in those with refractory hypertension: microalbuminuria indicates a high CV risk and must lead to strict control of arterial pressure. Studies focused on microalbuminuria in non-diabetic non-hypertensive subjects are limited; most of them suggest that microalbuminuria predicts CV complications and deleterious outcome. Subjects with a history of CV or cerebrovascular disease have an even greater CV risk if microalbuminuria is present than if it is not; however, in all cases, therapeutic intervention must be aggressive regardless of whether microalbuminuria is present or not. It is not recommended to measure UAE in non-diabetic non-hypertensive subjects in the absence of history of renal disease. Monitoring of renal function (UAE, serum creatinine and estimation of GFR) is recommended annually in all subjects with microalbuminuria. MANAGEMENT: In patients with microalbuminuria, weight reduction, sodium restriction (<6 g per day), smoking cessation, strict glucose control in diabetic subjects, strict arterial pressure control are necessary; in diabetic subjects: use of maximal doses of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) are recommended; ACEI/ARB and thiazides have synergistic actions on arterial pressure and reduction of UAE; in non-diabetic subjects, any of the five classes of anti-hypertensive medications (ACEI, ARB, thiazides, calcium channel blockers or beta-blockers) can be used.

[Is hypertension related to the number of nephrons?]. / L'HTA est-elle déterminée par le capital néphronique?

The kidney has a key role in blood pressure control, and an abnormal regulation of sodium balance is involved in essential hypertension. It has been suggested that a reduced nephron number at birth could be one possible mechanism. Indeed various strains of hypertensive animals exhibit a reduced nephron number. In human beings, two autopsy studies have clearly shown a lower (about 50%) nephron number in hypertensive subjects. The glomeruli are also enlarged, indicating hyperfiltration. This could be the cause of both high blood pressure and later nephrosclerosis. A low number of nephrons is part of the perinatal programming which occurs together with fetal growth retardation, and this has been reproduced experimentally. There is a negative correlation between birth weight and glomerular number. Such a situation is associated with a largely increased risk of cardiovascular complications in adulthood.

[Pregnancy-related hypertension]. / Hypertensions gravidiques.

PURPOSE: Hypertension occurs in 10 to 15 p cent of pregnancies. Among them, 10 to 20% also have proteinuria. This situation defines preeclampsia, and involves a serious threat on fetal and even maternal prognosis. Presence of the hepatic (HELLP) syndrome still severely worsens the prognosis. CURRENT KNOWLEDGE AND KEY POINTS: Pathophysiology of preeclampsia is based on a very early abnormality of placentation, leading to insufficient blood supply to the feto-placental unit. At the maternal level, the main consequence of placental ischemia is generalized endothelial dysfunction, responsible for systemic vasoconstriction and clotting abnormalities. In such a context, lowering blood pressure with drugs is quite inefficient, or even harmful. The prognosis of this disease is mainly related to the pertinence of obstetrical management. FUTURE PROSPECTS AND PROJECTS: An early preventive strategy is the most logical approach of preeclampsia, its modalities remain under discussion.

[Hypertension in pregnancy]. / Hypertensions gravidiques.

Hypertension occurs in 10 to 15 p cent of pregnancies. Among them, 10 to 20% also have proteinuria. This situation defines preeclampsia, and involves a serious threat on foetal and even maternal prognosis. Presence of the hepatic (HELLP) syndrome still severely worsens the prognosis. Pathophysiology of preeclampsia is based on a very early abnormality of placentation, leading to insufficient blood supply to the foeto-placental unit. At the maternal level, the main consequence of placental ischemia is diffuse endothelial dysfunction, responsible for systemic vasoconstriction and clotting abnormalities. In such a context, merely lowering blood pressure with drugs is quite inefficient, or even harmful. The prognosis of this disease is mainly related to the pertinence of obstetrical management. An early preventive strategy is the most logical approach of preeclampsia, its modalities remain under discussion. Hypertension has a high recurrence rate on subsequent pregnancies. It is most often linked to a high global vascular risk level, therefore many of those patients will become permanent hypertensives in the near future.

[Aspirin and prevention of pre-eclampsia]. / Aspirine et prévention de la prééclampsie.

Aspirin is used in pregnant women in order to obviate the imbalance of prostanoids caused by a defective placentation, and also to counteract the widespread thrombotic tendency related to endothelial dysfunction. After a series of controlled trials which showed a very consistent effect of aspirin t prevent preeclampsia and fetal growth retardation, several recent large trials have cast the doubt, and even unbelief. Their results are analyzed in an explicative way. Discrepancies seem largely related to either studying very low-risk populations, or strong differences in aspirin dosage and/or term of introduction. In the last few years, several works have shown the critical importance of an early treatment, and also of a measurable biologic effect, which requires larger dosages than those used in the most recent trials. The doubt largely remains as for the adequate indications of this treatment. New data in the physiology of placentation suggest that it would be logical to give aspirin as early as the first wave of throphoblastic invasion. The effect of so an early treatment need to be evaluated. The search for early markers should be pursued. The combination of aspirin and heparin is under investigation. Finally, other ways of prevention, such as anti-oxidants, are also being studied.

[Hypertension in women (contraception and menopause]. / Hypertensions de la femme (contraception et ménopause).

There are three circumstances where hypertension develops specifically in women: oral contraception, pregnancy, and menopause. Oral contraception usually shifts the blood pressure moderately upwards, but hypertension appears in less than 5% of women. Still it may (rarely) be very severe. Hypertension is poorly related to the dosage of the estrogenic compound, but rather to the nature and dosage of the progestive part. This hypertension does not significantly increase the cardiovascular risk of these women. The role of menopause itself in the trigging of hypertension remains uncertain. It seems however that confounding factors such as age, body weight, sodium balance and so on explain the increased incidence of hypertension after menopause. The latter is also associated with an increase of cardiovascular risk, which requires adequate treatment. Hormone replacement therapy is not contra-indicated, even in hypertensive patients.

[Arterial hypertension of the pregnant woman]. / L'hypertension artérielle de la femme enceinte.

Pregnancy hypertension remains a frequent disease, sometimes seriously threatening mother and fetus. Its primum movens has been shown to be an abnormal placentation and/or trophoblastic invasion. This abnormality is triggered by various factors which can be immunologic, vascular, or abnormalities of hemostasis. This defective placentation results in a systemic endothelial disease with vasoconstriction and widespread thrombotic tendency. Antihypertensive treatment is of very poor efficiency, and even may worsen the fetal situation through underperfusion. Early prevention is clearly a better way to improve the prognosis. Low-dose aspirin is widely used, although its efficiency has been debated recently, after the publication of negative results. It is likely that proper selection of patients, as well as the timing and dosage of treatment, are key factors for its efficiency.

Effect of aspirin in pregnant women is dependent on increase in bleeding time.

OBJECTIVES: Randomized trials with low-dose aspirin to prevent preeclampsia and intrauterine growth restriction have yielded conflicting results. In particular, 3 recent large trials were not conclusive. Study designs, however, varied greatly regarding selection of patients, dose of aspirin, and timing of treatment, all of which can be determinants of the results. Retrospectively analyzing the conditions associated with failure or success of aspirin may therefore help to draw up new hypotheses and prepare for more specific randomized trials. STUDY DESIGN: We studied a historical cohort of 187 pregnant women who were considered at high risk for preeclampsia, intrauterine growth restriction, or both and were therefore treated with low-dose aspirin between 1989 and 1994. Various epidemiologic, clinical, and laboratory data were extracted from the files. Univariate and multivariate analyses were performed to search for independent parameters associated with the outcome of pregnancy. RESULTS: Age, parity, weight, height, and race had no influence on the outcome. The success rate was higher when treatment was given because of previous poor pregnancy outcomes than when it was given for other indications, and the patients with successful therapy had started aspirin earlier than had those with therapy failure (17.7 vs 20.0 weeks' gestation, P =.04). After multivariate analysis an increase in Ivy bleeding time after 10 days of treatment by >2 minutes was an independent predictor of a better outcome (odds ratio 0.22, 95% confidence interval 0.09-0.51). Borderline statistical significance was observed for aspirin initiation before 17 weeks' gestation (odds ratio 0.44, 95% confidence interval 0.18-1. 08). Abnormal uterine artery Doppler velocimetric scan at 20-24 weeks' gestation (odds ratio 3.31, 95% confidence interval 1.41-7.7), abnormal umbilical artery Doppler velocimetric scan after 26 weeks' gestation (odds ratio 37.6, 95% confidence interval 3.96-357), and use of antihypertensive therapy (odds ratio 6.06, 95% confidence interval 2.45-15) were independent predictors of poor outcome. CONCLUSIONS: Efficacy of aspirin seems optimal when bleeding time increases >/=2 minutes with treatment, indicating a more powerful antiplatelet effect. This suggests that the dose of aspirin should be adjusted according to a biologic marker of the antiplatelet effect. A prospective trial is warranted to test this hypothesis.