Jean-Pierre Fauvel

Estimating glomerular filtration rate in kidney transplant recipients: performance over time of four creatinine-based formulas.

Background. The management of kidney transplant recipients requires accurate estimate of glomerular filtration rate (GFR). This study aims at evaluating the performance of four creatinine-based formulas for estimating the GFR (estimated GFR) in this population. Methods. Performances of Cockcroft and Gault formula, Modification of Diet in Renal Disease (MDRD) simplified formula, Chronic Kidney Disease Epidemiology Collaboration formula, and Nankivell formula were assessed compared with inulin clearance taken as the gold standard for measuring GFR (measured GFR). Performances were assessed using the first measurements of GFR obtained in 1249 subjects. How estimated GFR tracks changes in measured GFR over time since transplantation in those patients with repeated measures was also assessed. Results. The MDRD formula provided the best estimate of GFR with a mean bias of −0.5 mL/min/1.73 m2, a standard deviation of bias of 12 mL/min/1.73 m2, and a 30% accuracy at 85%. The MDRD formula also seemed to provide the best performance for estimating GFR, irrespective of age, stage of renal failure, and in people whose body mass index was more than 18.5 kg/m2. This robustness is important in clinical practice. The performance of the four formulas was not modified by the posttransplant period. Conclusion. Even if 30% accuracy was suboptimal in the Kidney Disease Outcomes Quality Initiative guidelines, our results, obtained in a large number of patients, lead us to recommend using the MDRD formula to monitor GFR in kidney transplant recipients.

Biological, electrical and echocardiographic indices versus cardiac magnetic resonance imaging in diagnosing left ventricular hypertrophy

The aim of this study was to compare the diagnostic performance of N-terminal pro-brain natriuretic peptide (NT-proBNP), electrocardiographic (ECG) criteria and transthoracic echocardiography (TTE) versus cardiac magnetic resonance imaging in detecting left ventricular hypertrophy (LVH). The study included 42 hypertensive subjects with mean±s.d. age 48.1±12.3 years, 57.1% men, 24-h ambulatory blood pressure 144/89 mm Hg, left ventricular ejection fraction >50%, without symptoms of heart failure, and not taking any drugs that interfere with hormonal regulation. The accuracies of the methods in detecting LVH were compared at two diagnostic LVH cutoffs: low, 83 g m−2 in men and 67 g m−2 in women; and high, 96 g m−2 in men and 81 g m−2 in women. With the low and high LVH cutoffs, the areas under the receiver-operating characteristic curves and the optimal values for NT-proBNP were 0.761, 0.849, 200 and 421 pg ml−1, respectively. An NT-proBNP level under 30 pg ml−1 ruled out LVH with 100% sensitivity. The optimal values and literature-based values of NT-proBNP allowed a correct classification of 73–81% of the subjects. In 80–90% of the cases, the diagnostic accuracy of NT-proBNP was close to that of ECG criteria but lower than that of TTE criteria. Interestingly, combining ECG criteria and NT-proBNP level improved the diagnostic performance to be at least comparable to that of TTE: the percentages of correctly classified subjects were 73–95% vs. 67–86%, respectively. Of note, the range considers both diagnostic LVH cutoffs. The simultaneous use of ECG criteria and NT-proBNP plasma levels seemed to be powerful enough to detect LVH in most hypertensive subjects.

Is there a BP benefit of changing the time of aspirin administration in treated hypertensive patients

Background and design: The effects of aspirin on blood pressure (BP) are controversial and a chronopharmacological effect of aspirin on 24-hour BP was reported recently in otherwise untreated hypertensive patients. The study was designed to test the timing effect of aspirin dosing on 24-hour BP in treated hypertensive patients routinely taking aspirin for cardiovascular prevention. Method and results: Seventy-five patients were randomized into two groups. One group was to receive aspirin in the evening then in the morning for 1 month and the other group in the morning then in the evening, following a cross-over design. The principal assessment criterion was 24-hour systolic BP (SBP) measured by 24-hour ambulatory BP monitoring (ABPM). Patients were aged 65 ± 9 years and had been hypertensive for 12 ± 10 years. They were all taking a mean of 2.8 antihypertensive drugs and did not modify their treatment throughout the study. Of the included subjects, 70% were men and 33% were diabetics. Mean 24-hour SBP values were clinically equivalent and were not statistically different, depending on whether the aspirin was taking in the morning or evening (128.3 ± 1.4 vs. 128.3 ± 1.4 mmHg, respectively). Neither was there any significant difference in diurnal and nocturnal SBP or in 24-hour, diurnal, and nocturnal diastolic BP (DBP). Conclusion: It does not appear useful to advise patients with long-standing hypertension to modify timing of aspirin intake in order to reduce BP values.

Microalbuminurie et excrétion urinaire d'albumine: recommandations pour la pratique clinique

Measurement of urinary albumin excretion (UAE) may be done on a morning urinary sample or on a 24 hours-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 μg/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.

Can we identify response markers to antihypertensive drugs? First results from the IDEAL Trial

Current antihypertensive strategies do not take into account that individual characteristics may influence the magnitude of blood pressure (BP) reduction. Guidelines promote trial-and-error approaches with many different drugs. We conducted the Identification of the Determinants of the Efficacy of Arterial blood pressure Lowering drugs (IDEAL) Trial to identify factors associated with BP responses to perindopril and indapamide. IDEAL was a cross-over, double-blind, placebo-controlled trial, involving four 4-week periods: indapamide, perindopril and two placebo. Eligible patients were untreated, hypertensive and aged 25–70 years. The main outcome was systolic BP (SBP) response to drugs. The 112 participants with good compliance had a mean age of 52. One in every three participants was a woman. In middle-aged women, the SBP reduction from drugs was −11.5 mm Hg (indapamide) and −8.3 mm Hg (perindopril). In men, the response was significantly smaller: −4.8 mm Hg (indapamide) and −4.3 (perindopril) (P for sex differences 0.001 and 0.015, respectively). SBP response to perindopril decreased by 2 mm Hg every 10 years of age in both sexes (P=0.01). The response to indapamide increased by 3 mm Hg every 10 years of age gradient in women (P=0.02). Age and sex were important determinants of BP response for antihypertensive drugs in the IDEAL population. This should be taken into account when choosing drugs a priori.

RecommandationMicroalbuminurie et excrétion urinaire d'albumine : recommandations pour la pratique cliniqueMicroalbuminuria and urinary albumin excretion: clinical practice guidelines

Measurement of urinary albumin excretion (UAE) may be done on a morning urinary sample or on a 24 hours-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 μg/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.

Hypertension artérielle du sujet noir

Points essentiels L’hypertension arterielle est plus frequente et plus severe chez le sujet noir. L’hypertension est plus volontiers sel-dependante et a renine basse. L’atteinte cardiovasculaire semble identique chez les sujets blancs et noirs et depend essentiellement des facteurs de risque cardiovasculaires classiques. L’atteinte renale est plus frequente chez les noirs, conduisant a une plus forte prevalence de l’insuffisance renale terminale. Au plan therapeutique, une normalisation de la consommation en sel potentialise le traitement. Si les diuretiques et les inhibiteurs calciques font plus baisser la pression arterielle des sujets noirs, les inhibiteurs du systeme renine angiotensine protegeraient mieux les organes cibles. Il est necessaire de mettre en place des essais therapeutiques specifiquement dedies a la connaissance des benefices therapeutiques chez les sujets noirs.

Management of resistant hypertension: expert consensus statement from the French Society of Hypertension, an affiliate of the French Society of Cardiology.

To improve the management of resistant hypertension, the French Society of Hypertension, an affiliate of the French Society of Cardiology, has published a set of eleven recommendations. The primary objective is to provide the most up-to-date information based on the strongest scientific rationale and that is easily applicable to daily clinical practice. Resistant hypertension is defined as uncontrolled blood pressure on office measurements and confirmed by out-of-office measurements despite a therapeutic strategy comprising appropriate lifestyle and dietary measures and the concurrent use of three antihypertensive agents including a thiazide diuretic, a renin-angiotensin system blocker (ARB or ACEI) and a calcium channel blocker, for at least 4 weeks, at optimal doses. Treatment compliance must be closely monitored, as must factors that are likely to affect treatment resistance (excessive dietary salt intake, alcohol, depression, drug interactions and vasopressor drugs). If the diagnosis of resistant hypertension is confirmed, the patient should be referred to a hypertension specialist to screen for potential target organ damage and secondary causes of hypertension. The recommended treatment regimen is a combination therapy comprising four treatment classes, including spironolactone (12.5–25 mg per day). In the event of a contraindication or a non-response to spironolactone, or if adverse effects occur, a β-blocker, an α-blocker, or a centrally acting antihypertensive drug should be prescribed. Because renal denervation is still undergoing assessment for the treatment of hypertension, this technique should only be prescribed by a specialist hypertension clinic.

Major cardiovascular risk factors are not taken into account by physicians when targeting blood pressure values for uncontrolled hypertensive patients.

BACKGROUND The main factors studied possibly explaining inadequate blood pressure (BP) control in the population are related either to treatment or to patients. Subjective behavior of physicians might also explain insufficient BP control in the population. This study analyzed the consistency between systolic BP (SBP) targets set by physicians for uncontrolled hypertensive patients and the guidelines according to cardiovascular (CV) risk factors. METHODS A total of 993 general practitioners completed 2,455 questionnaires which included items related to the clinical and biological characteristics of uncontrolled hypertensive patients. At the end of each questionnaire, physicians noted the SBP level they targeted for each patient. The coronary heart disease (CHD) risk score was computed for each patient according to the Framingham study. RESULTS The mean SBP target set by physicians was 136 +/- 6 mm Hg. However, in 24% of the patients, SBP targets set by physicians were higher than those recommended and, above all, the higher the Framingham CHD risk score, the lower the percentage of subjects with correctly targeted SBP goals. SBP values targeted by physicians were higher than recommended goals mostly in patients with diabetes and/or renal impairment. Interestingly, the targeted SBP was significantly and positively correlated with the previously determined office SBP (r = 0.26, P < 0.001). CONCLUSIONS The higher the CV risk, the lower the number of patients with targeted SBP in accordance with guidelines. When considering CV risk factors, physicians did not take into account that a lower BP goal is advocated for patients with diabetes and renal impairment.

Effect of Beta-Blockade on Albumin Excretion Rate in Essential Hypertension

Maurice Laville, MD, Pavilion P., Hôpital Edouard-Herriot, F-69437 Lyon Cedex 03 (France) Dear Sir, The excretion of small amounts of albumin, called microalbuminuria, is well known as an early feature of glomerular impairment in diabetics. It has also been observed in patients with essential hypertension [1–3], as a consequence of altered renal hemodynamics with increased glomerular capillary pressure. In diabetics, an-giotensin converting enzyme inhibitors (ACEI) have proved their ability to reduce albumin excretion rate (AER), a fact attributed to an elective vasodilation of postglomerular arteries [4]. In hypertensives however, a decrease in AER has been reported after normalization of blood pressure by antihypertensive drugs with different hemodynamic effects [1]. Thus, we designed a prospective study of the effect of an 8-week ß-blocker treatment on microalbuminuria in essential hypertensives. Fourteen patients (10 men and 4 women, mean age 46.8 ± 11.3 years, range 27–65) entered the study. They had mild essential hypertension (inclusion DBP 97.5 ± 7.1 mm Hg) for 5.2 ± 4.1 years. All of them had normal renal function measured by creatinine clearance, without macroalbuminuria or hematuria on dipstick uri-nalysis. None was yet treated by antihypertensive drugs at inclusion. In previously treated patients, all antihypertensive drugs were progressively withdrawn, and a 2-week wash-out period was performed before testing. All patients received a cardioselective ß-blocker, bis-oprolol, which lacks ß-agonist activity. The drug was taken at a dosage of 10 mg once a day, in the morning, even the day of visits, during 8 weeks as the sole therapy. The following measurements were performed the day before and after 2 months of treatment. Patients were requested to collect 24-hour urine the day before the test, then came in the morning as outpatients to the Nephro-logy Department where blood and urine samples were taken after 1 h of rest in supine position. During this period, blood pressure was measured every 6 min using an automated oscillometric device (Dinamap®). The mean of the 10 blood pressure readings was used for comparisons. Creatinine was measured on blood and urine samples by an automated Jaffé method and its clearance calculated. Albumin was measured on 24-hour and 1hour urine using immunoturbidimetry (Turbitimer, Behringwerke AG, Marburg, FRG). This method provides a sensitivity treshold of 6 mg/l with an intra-assay variation coefficient of 3% in