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Biomedical subjects

Maurice Laville

Publications and source records attributed to Maurice Laville.

At least 19 recordsLinked to original sources

[Proteinuria].

Several health organizations recommend that people be regularly checked for proteinuria to detect and treat kidney disease before it progresses. Proteinuria detected by a simple dipstick test should be confirmed by a quantitative measurement to assess persistent proteinuria. Most proteins are too big to pass through the kidneys' filters into the urine unless the kidneys are damaged. Markers of kidney damage in addition to proteinuria include abnormalities in the urine sediment, ultrasound of the kidneys and estimation of kidney function (creatinemia to calculate glomerular filtration rate). These assessments provide clues to the type (diagnosis) of chronic kidney disease and will the risk for developing progressive kidney failure. Thus, early detection of kidney disease will result in a more timely introduction of therapy that may slow the course of kidney disease. Microalbuminuria (albumin excretion above the normal range) that a marker of microvascular lesions in diabetes and hypertension is associated with a worth cardiovascular prognosis. Level of proteinuria in excess of 3,0 g/d in glomerular disease strongly determines the extent of kidney damage and renal prognosis.

Glomerular Filtration Rate↗

[Hypertension in blacks].

Hypertension is more frequent and more severe in blacks than in other racial groups. Salt-sensitive and low-renin hypertension are both more frequent in blacks. Cardiovascular morbidity appears to be similar in blacks and whites and depends on the classic cardiovascular risk factors. Kidney damage leading to end-stage renal disease is more frequent in blacks. Reduced salt intake improves drug efficacy. Diuretics and calcium channel blockers are more effective in lowering blood pressure, while angiotensin-converting-enzyme inhibitors may be more effective in preventing organ damage. Specific trials are needed to evaluate therapeutic benefits in blacks.

Angiotensin-Converting Enzyme Inhibitors↗

Recurrent idiopathic thrombotic thrombocytopenic purpura: a role for vaccination in disease relapse?

The presence of antibodies against a disintegrin-like metalloproteinase with thrombospondin type 1 motif, isoform 13 (ADAMTS 13 protease) is the main cause (70% to 80%) of idiopathic and recurrent thrombotic thrombocytopenic purpura (TTP). However, etiologic factors that trigger the onset and potential relapses of TTP remain unclear. Immunologic deregulation and infectious agents are suspected. We report the case of a 51-year-old white man presenting with idiopathic TTP caused by autoantibodies against ADAMTS 13 protease. The first acute TTP episode needed long-term plasma exchanges because of early relapses. Consequently, vincristine therapy and splenectomy were performed. Those treatments induced TTP remission for 18 months. Relapses occurred twice between 1 and 3 months after vaccination. However, those relapses were not as severe as the first acute episode and responded to short-course plasma exchanges. ADAMTS 13 antibodies and decreased ADAMTS 13 protease activity were searched for and detected first during the second relapse. This case challenges the role of vaccination as an etiologic factor in the recurrence of idiopathic TTP.

ADAM Proteins↗

Is hypertension a tissue perfusion disorder? Implications for renal and myocardial perfusion.

Structural alterations in the microcirculation form a major link between hypertension and target organ damage. More than 60% of the overall peripheral resistance of the circulatory system arises at the level of the microcirculation. The primary function of the microcirculation is to supply oxygen and nutrients to tissues. In hypertension, remodelling of the microvascular vessels occurs, leading to an early, functional then anatomical reduction in the number of arterioles or capillaries in a given vascular bed. Such changes have been seen in the structure and density of the microvasculature of different target organs such as the myocardium and the kidneys. In hypertension, capillary rarefaction induces an increase in blood pressure, a relative decrease in tissue perfusion and an increased cardiovascular risk. Recent in-vivo non-invasive techniques for exploring the human microcirculation have allowed the detection of myocardial and renal microvascular impairment in hypertensive patients. In comparative therapeutic studies, antihypertensive drugs have been shown to have different capacities for preventing or reversing changes to the microvasculature of affected organs.

Adrenergic beta-Antagonists↗

A French cost-consequence analysis of the renoprotective benefits of irbesartan in patients with type 2 diabetes and hypertension.

OBJECTIVES: We performed a cost-consequence analysis in a French setting of the renoprotective benefit of irbesartan in hypertensive type 2 diabetes patients over a 25-year period. RESEARCH DESIGN AND METHODS: A previously published Markov model simulated progression from microalbuminuria to overt nephropathy, doubling of serum creatinine, end-stage renal disease and death. Three treatment strategies with analogous blood pressure control were compared: (A) control--conventionally medicated antihypertensive therapy (excluding angiotensin converting enzyme inhibitors, other angiotensin-2-receptor antagonists and dihydropyridine calcium channel blockers) initiated at microalbuminuria; (B) early irbesartan--(300 mg daily added to control, initiated with microalbuminuria) and (C) late irbesartan--(300 mg daily, initiated with overt nephropathy). Probabilities came from the Irbesartan in Reduction of Microalbuminuria-2 study, Irbesartan in Diabetic Nephropathy Trial and other sources. Clinical and economic outcomes were projected over 25 years. Annual discount rates were 3%. RESULTS: Compared to control, early use of irbesartan added (mean +/- standard deviation) 1.51 +/- 0.08 undiscounted life years (discounted: 0.94 +/- 0.05 years), while late irbesartan added 0.07 +/- 0.01 (0.04 +/- 0.01) years/patient. Early irbesartan added 1.03 +/- 0.06 discounted quality-adjusted life years (QALYs), while late irbesartan added 0.06 +/- 0.01 QALYs. Early and late irbesartan treatments were projected to save 22,314 +/- 1273 euro and 6619 +/- 820 euro/patient, respectively versus control. Sensitivity analysis showed that even over short time horizons both irbesartan treatments were superior to the control group. CONCLUSIONS: In France, early irbesartan treatment improved quality and length of life and reduced costs in hypertensive patients with type 2 diabetes and microalbuminuria. Late irbesartan therapy is beneficial, but earlier irbesartan leads to better outcomes.

Albuminuria↗

[Choosing between peritoneal dialysis and haemodialysis: a critical appraisal of the literature].

In France, incidence and prevalence of end-stage renal disease (ESRD) are increasing, requiring a more rational use of available replacement therapies. To help practitioners make their choice between treatment modalities of peritoneal dialysis (PD) and haemodialysis (HD), critical appraisal of relevant literature has been conducted. Although few absolute or relative contraindications for PD and HD exist, arguments in favour of one versus the other dialysis technique can be made. When patients receive adequate and complete information, their preference is neutral between PD and HD. To date, no trial presenting a convincing level of evidence has been published which demonstrates the superiority of one technique compared to the other. Relative to mortality, it appears that no difference can be observed between the two modalities. However, in those instances where patients expect a rapid transplantation, PD is the preferred technique. This analysis suggests that peritoneal dialysis and haemodialysis are not competitive but rather complementary treatments. It is therefore interesting to identify the reasons supporting the various choices between the two different treatment modalities amongst France's regions. Access to transplant, economic or organizational factors must be considered.

Contraindications↗

Dialyzer membrane permeability and survival in hemodialysis patients.

BACKGROUND: We previously showed that nutritional protein concentrations were predictive of outcome, whereas variables reflecting body composition and dialysis dose were not, in a 30-month prospective follow-up of 1,610 hemodialysis patients. Information on dialysis membrane and erythropoietin use had to be evaluated in an additional follow-up. METHODS: A subset of 650 patients from the initial cohort of 1,610 was analyzed for survival in a 2-year extension of follow-up. Detailed data were collected: demographics; cause of renal failure; time on dialysis therapy; type of membrane; erythropoietin treatment; body mass index (BMI); predialysis albumin, prealbumin, and bicarbonate levels; and outcome. Normalized protein catabolic rate (nPCR), dialysis adequacy, and lean body mass were computed from predialysis and postdialysis urea and creatinine values. RESULTS: Patient characteristics were age of 61 +/- 16 years, 58% men, BMI of 22.7 +/- 4.4 kg/m2 , time on dialysis therapy of 102 +/- 73 months, and 8.8% had diabetes. Dialysis parameters were duration of 247 +/- 31 minutes, Kt/V of 1.4 +/- 0.3, and nPCR of 1.2 +/- 0.3 g/kg/d. Albumin level was 3.73 +/- 0.53 g/dL (37.3 +/- 5.3 g/L), and prealbumin level was 31 +/- 8 mg/dL. The survival rate was 78.7% after 2 years. Survival was influenced by age, presence of diabetes, use of high-flux membrane, and serum albumin level, but not other variables, including Kt/V and prealbumin level. Two-year variations in values for urea, creatinine, and weight were predictive of survival in univariate, but not multivariate, analyses. CONCLUSION: In patients on dialysis therapy for a long period, better survival was observed when high-flux dialysis membranes were used.

Aged↗

[Hypertension in patients with chronic renal disease].

Hypertension belongs to the clinical picture of chronic renal disease (CRD). Its frequency depends on the type of nephropathy and the stage of CRD. Whatever the primary renal disease, more than 80% of patients beginning dialysis do have hypertension. The pathophysiology of hypertension in those patients involves a hyperactivity of renin-angiotensin system, as well as a decrease of sodium excretion capacity accompanying the decrease in glomerular filtration rate. Hypertension is the leading factor of renal disease progression as suggested by the relationship between blood pressure and function decay, and demonstrated by the results of antihypertensive intervention studies. The interaction between blood pressure and proteinuria is extremely detrimental. Hypertension is an important factor of cardiovascular risk excess observed in CRD patients, but the effect of antihypertensive treatment on cardiovascular risk remains limited in those patients, due to accumulation of other major risk factors. Finally, it is worth noting to mention the increasing place of vascular nephropathy, especially due to essential hypertension, amongst the causes of end-stage renal disease, where it compare with diabetic nephropathy accounting for 20% of incident patients in France.

Antihypertensive Agents↗

Comparison of different therapeutic strategies in hypertension: a low-dose combination of perindopril/indapamide versus a sequential monotherapy or a stepped-care approach.

OBJECTIVE: To compare the efficacy and the tolerability of three different strategies in the treatment of hypertension (low-dose combination, sequential monotherapy and stepped-care). DESIGN: Hypertensive patients were randomized to a 9-month treatment with the aim to lower blood pressure below 140/90 mmHg. Treatment adjustments were allowed at months 3 and 6. The study was discontinued for patients with normal blood pressure at month 6. In the 'low-dose combination' group, perindopril (2 mg) and indapamide (0.625 mg) were first administered with the possibility to increase the doses in two steps up to respectively, 4 and 1.25 mg. In the 'sequential monotherapy' group, the treatment was initiated with atenolol (50 mg), replaced if necessary by losartan (50 mg), and then by amlodipine (5 mg). In the 'stepped-care' group, valsartan, was given first at a 40 mg dose, then at a 80 mg dose, to be co-administered finally if needed with hydrochlorothiazide, 12.5 mg. All study tablets were encapsulated to conceal their identity and had to be taken once a day. PATIENTS: Patients with uncomplicated essential hypertension were recruited (n = 180 in the 'low-dose combination' group, n = 176 in the 'sequential monotherapy' group and n = 177 in the 'stepped-care' group). RESULTS: The percentage of patients having achieved the target blood pressure was significantly greater in the 'low-dose combination' group (62%) than in the 'sequential monotherapy' (49%, P = 0.02) and the 'stepped-care' group (47%, P = 0.005). The percentage of patients having normalized their blood pressure without experiencing drug-related adverse events was also significantly higher in the 'low-dose combination' group (56%) than in the 'sequential monotherapy' (42%, P = 0.002) and the 'stepped-care' group (42%, P = 0.004). CONCLUSIONS: A first line management of hypertension based on a low-dose combination of perindopril and indapamide allows the normalization of blood pressure in significantly more patients than a 'sequential monotherapy' strategy involving atenolol, losartan and amlodipine, and a 'stepped-care' strategy involving valsartan and hydrochlorothiazide. These better blood pressure results were not obtained at the expense of a worsening of tolerability.

Aged↗

Neither perceived job stress nor individual cardiovascular reactivity predict high blood pressure.

We have reported that high job strain was associated with a significantly higher diastolic blood pressure (DBP) of 4.5 mm Hg during the working hours, irrespective of BP reactivity to a stress test. We report the final results of the first 5-year follow-up study, which aimed to assess the respective influences of perception of professional strain and cardiovascular reactivity to a mental stress test on BP. A cohort of 292 healthy subjects (mean+/-SEM age, 38+/-1 years) was followed up for progression to hypertension outcome, which was defined as an increase in systolic blood pressure (SBP) or DBP >7 mm Hg or a DBP >95 mm Hg during follow-up. None of the subjects was lost to follow-up, and 209 subjects completed the study. The high-strain (HS) group, representing 20.9% of the subjects, was compared with the remaining subjects (non-high-strain [NHS]). Similarly, the subjects with the highest BP stress reactivity (HR; 20.9% of subjects) were compared with the remaining subjects (NHR). Progression to hypertension was reached by 93 subjects (31.8%). Kaplan-Meier survival estimates revealed that neither HS nor HR increased the incidence of progression to hypertension. End-of-follow-up 24-hour ambulatory BPs that were similar in HS and NHS (120+/-2 vs 120+/-1 mm Hg, respectively) and in HR and NHR (122+/-2 vs 120+/-1 mm Hg, respectively) confirmed our findings. Age, alcohol, salt diet, body mass index, and occupation did not interfere with our results. In conclusion, cardiovascular HR and HS do not appear to be major risk markers for future high BP in healthy, young adults.

Adolescent↗

Ischemia induces early expression of a new transcription factor (6A3-5) in kidney vascular smooth muscle cells: studies in rat and human renal pathology.

Acute renal failure, characterized by rapid decline in glomerular filtration rate, is a major cause of morbidity and mortality. During the evolution of renal diseases chronic ischemia develops. Indeed, acute or chronic renal failure may occur as a result of renal ischemia, which induces cells to dedifferentiate, proliferate, or become apoptotic. In this study, we have investigated the expression of a newly identified transcription factor, 6A3-5, under in vitro and in vivo conditions. Proliferating vascular smooth muscle were investigated in response to different mitogenic agents. The 6A3-5 expression was then studied in ischemic rat kidney, induced by renal pedicle clamping, followed, or not, by reperfusion. Subsequently human renal biopsies from early kidney grafts and chronic renal diseases were also investigated for 6A3-5 protein expression by immunohistochemistry. In vitro study shows an over-expression of 6A3-5 following 2 to 4 hours stimulation by serum or Angiotensin II, of rat proliferating aortic smooth muscle cell. Moreover, in vivo study shows that this new protein is over expressed in rat kidney submitted to 45 minutes ischemia. An anti-6A3-5 antibody shows the protein to be expressed in smooth muscle cells of the arterioles and intermediate size arteries, in mesangial cells and interstitial myofibroblasts. In human biopsies of early kidney grafts and renal disease, the same up-regulation of 6A3-5, as in acute ischemic situation, is observed. This 6A3-5 expression is intimately associated with alpha-smooth muscle cell actin expression in mesangial cells, arteriolar smooth muscle cells as well as interstitial myofibroblasts. Transcription factor 6A3-5 could potentially be a novel early vascular marker of acute and chronic renal ischemic stress implicated in tissue remodeling.

Animals↗

Advances in anabolic interventions for malnourished dialysis patients.

Malnutrition is a frequent state during maintenance dialysis. Among a variety of reasons, chronic catabolic events as well as resistance to anabolic compounds do induce an imbalance in protein metabolism and favor a chronic loss in protein mass. Anabolic effects have been obtained in pilot studies with recombinant growth hormone and insulin-like growth factor-1 in adult dialysis patients. More recently, the come back of androgen therapy provided reports of a positive impact on body composition and physical activity during maintenance dialysis. Strong improvement in nutritional status has also been obtained by more frequent dialysis sessions, either during long nocturnal or short daily schedules. Thus, promising new therapies are emerging to fight the important incidence of malnutrition in dialysis patients.

Androgens↗

Predicted creatinine clearance to evaluate glomerular filtration rate in black Caribbean subjects.

BACKGROUND AND METHODS: Although Caribbean people have been a lesser-studied ethnic group than other populations, they have a high burden of hypertension and renal disease. Because Caribbean people have a greater muscle mass than Caucasians, this study examined the accuracy of creatinine-based estimates (creatinine clearance; C(cr) and Cockcroft-Gault formula; C-G Cl) of glomerular filtration rate (GFR) in 38 Caribbeans who were matched for age, gender, and GFR, with 38 Caucasian subjects. Patients were considered black Caribbean if at least one of two parents was of black Caribbean origin. GFR values ranging from 5 to 140 ml/min/1.73 m(2) were measured by inulin clearance. Results were compared using linear correlations and the Bland and Altman methodology to provide better estimates of value dispersion. RESULTS: Correlation coefficients between C-G Cl and GFR were highly significant in both black Caribbean subjects (r=0.83, P<0.001) and Caucasians (r=0.84, P<0.001). Similar coefficients were obtained between C(cr) and GFR (r=0.89, P<0.001 and r=0.90, P<0.001, respectively). In spite of these strong correlations, the Bland and Altman representation highlighted huge intra-individual variations in GFR estimation by C-G Cl and by C(cr) in both ethnic groups. The underestimation of GFR by C-G Cl was significant in black Caribbeans (-8.6+/-20 ml/min/1.73 m(2), P<0.001) but not in Caucasians (-5.6+/-20.7 ml/min/1.73 m(2)). C(cr) overestimation of GFR was significant both in Caribbeans (8.7+/-16.8 ml/min/1.73 m(2), P<0.001) and in Caucasians (7.2+/-15.7 ml/min/1.73 m(2), P<0.01). CONCLUSIONS: The C-G formula for estimating GFR yields similar clinical values in black Caribbeans and in Caucasians, but the same limitations were observed in both ethnic groups.

Adult↗

Sodium intake and blood pressure in healthy individuals.

OBJECTIVE: To investigate further the relationships between blood pressure and sodium intake, which have been claimed to exist, but have not been clearly established, in epidemiological studies. DESIGN AND PARTICIPANTS: A 2-year follow up study of a cohort of 296 healthy volunteers working in the same company. RESULTS: Consistent with previously reported findings, covariance analysis in the entire population, including multivariate analysis to examine the potential influence of confounding variables, failed to identify a significant relationship between blood pressure and sodium intake or between their respective changes within 2 years. To test the hypothesis of a heterogeneous distribution of salt sensitivity, we calculated the statistical dependence between blood pressure and sodium intake using the coefficient analysis that quantifies the prevalence of a statistical link between two variables. A significant dependence (P < 0.05) between diastolic (DBP) or systolic (SBP) blood pressure and sodium intake was found in 16 and 5% of the participants, respectively. The analysis of the 2-year changes in blood pressure and sodium intake reinforced our findings. Our finding of a relationship between blood pressure and sodium intake in only a few individuals may explain the lack of a global relationship between these two variables investigated by the covariance analysis in our study.(Rho) CONCLUSION: Our results suggest that 5-16% of healthy individuals have a 'salt-dependent blood pressure' and might benefit from a reduction in dietary salt intake.

Adult↗

Stress-induced renal alterations in normotensives offspring of hypertensives and in hypertensives.

BACKGROUND: Scarce information is available on stress-induced renal behavior in humans, especially in normotensives offspring of hypertensives (HP) and in hypertensives (HT). METHODS: Ten HP and 10 HT were compared to 10 normotensives with normotensive parents (NP). Systolic blood pressure (SBP) and renal functional parameters were determined during rest and stress periods. RESULTS: The stress SBP reactivity was significantly (P < .05) higher in HP than in NP and HT. At rest, HP were characterized by a significantly (P < .05) higher glomerular filtration rate. Stress significantly reduced glomerular filtration rate (-14 +/- 4 mL/min/1.73 m2, P < .05) only in HT. Renal plasma flow significantly (P < .05) decreased during stress in NP (-35 +/- 16 mL/min/1.73 m2) and in HT (-49 +/- 25 mL/min/1.73 m2), whereas it did not change in HP. The resulting filtration fraction increased significantly during stress only in NP (1.5% +/- 0.6%, P < .05). Despite the increase in BP, stress induced a similar decrease in sodium excretion rate in NP (-52 +/- 26 micromol/min) and in HT (-56 +/- 24 micromol/min). The stress-induced sodium reabsorption occurred only in the proximal part of the tubules (lithium clearance). In HP, stress did not alter either sodium excretion rate or plasma renin activity. CONCLUSIONS: The stress-induced renal modifications are characterized by an efferent vasoconstriction and a paradoxical increase in sodium reabsorption that occurred in the proximal part of the tubules in NP. In HP, genetically at risk of hypertension, basal renal alterations may explain a different stress-induced renal behavior. In HT, stress-induced increase in sodium reabsorption may be involved in the sustained BP level.

Aldosterone↗

Malnutrition in hemodialysis diabetic patients: evaluation and prognostic influence.

BACKGROUND: This work aimed to evaluate the role of malnutrition in the increased mortality rate of hemodialysis diabetic patients from a French cooperative series. METHODS: Body mass index (BMI), serum albumin, prealbumin, cholesterol, and pre-dialysis creatinine, normalized protein catabolic rate and lean body mass (LBM) were measured in 734 diabetic and 6389 non-diabetic patients (aged 63.4 +/- 12.2 and 62.0 +/- 15.9 years; 1.01 male to 1.40 female ratio). The outcome of 1610 of these patients, including 170 diabetics, was assessed during a 30-month follow-up. RESULTS: Diabetic as compared to non-diabetic patients showed a significant (P < 10-4) increased BMI (25.9 +/- 5.2 vs. 23.1 +/- 4.3) and cholesterol (5.5 +/- 1.6 vs. 5.3 +/- 1.5 mmol/L), and decreased albumin (37.8 +/- 5.4 vs. 38.9 +/- 5.3 g/L), prealbumin (317 +/- 91 vs. 340 +/- 94 mg/L), creatinine (711 +/- 184 vs. 816 +/- 217 micromol/L) and LBM (76 +/- 18 vs. 87 +/- 21%). Normalized protein catabolic rate was similar in the two groups (1.11 +/- 0.31 vs. 1.13 +/- 0.32 g/kg/L). One and two-year survival was 83.7 +/- 2.9% and 65.5 +/- 3.8% in diabetic patients versus 90.3 +/- 0.8% and 79.9 +/- 1.1% in non-diabetics (relative risk 1.26, P < 0.01). Independent predictors of survival were age, albumin and prealbumin in non-diabetics and only age in diabetics. CONCLUSION: Diabetic patients compared to non-diabetics were characterized by an increased incidence of protein malnutrition and decreased survival. However, the higher death risk associated with diabetes was not related to malnutrition.

Aged↗

Dynamic renal blood flow measurement by positron emission tomography in patients with CRF.

BACKGROUND: Positron emission tomography (PET) is a functional imaging device that allows dynamic regional blood flow measurements. We performed a study to test whether PET could detect acute changes in renal blood flow (RBF) in patients with chronic renal failure (CRF). METHODS: RBF was measured by means of PET (PET-RBF) using oxygen 15-labeled water (H2(15)O) in eight men with hypertension and moderate CRF before and 5, 40, 80, and 120 minutes after the injection of quinaprilat (10 mg intravenously). Effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) were measured simultaneously by para-aminohippuric acid (PAH-ERPF) and inulin clearances before and 20, 60, 100, and 140 minutes after quinaprilat injection. RESULTS: Baseline RBF and ERPF were decreased in all patients (221 +/- 20 mL/min/100 g and 225 +/- 38 mL/min/1.73 m2, respectively). PET-RBF increased significantly after quinaprilat injection (+15%, +26%, +19%, and +23% versus baseline; P < 0.003). PAH-ERPF did not increase significantly (-6%, +12%, +20%, and +15% versus baseline; P = 0.15). GFR (50.1 +/- 8.9 mL/min/1.73 m2 at baseline) did not change significantly after quinaprilat injection; however, filtration fraction (GFR-ERPF ratio) decreased significantly from 0.23% +/- 0.02% to 0.20% +/- 0.02% (P = 0.0004). Mean arterial pressure decreased significantly after quinaprilat injection (P < 0.005). CONCLUSION: This study dynamically measured RBF by means of PET in patients with CRF for the first time. It showed that RBF rapidly increased after quinaprilat injection. PET using H2(15)O is a powerful method for the noninvasive measurement of dynamic changes in RBF that remain undetected by PAH clearance.

Adolescent↗