Maurice Laville

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.

Early impairment of trabecular microarchitecture assessed with HR-pQCT in patients with stage II-IV chronic kidney disease.

Bone fragility is a complication of chronic kidney disease (CKD). The aim of this study was to assess whether volumetric bone mineral density (vBMD) and microarchitecture could be impaired early in the course of CKD. Bone microarchitecture was examined with a noninvasive 3D imaging technique [high‐resolution peripheral quantitative computed tomography (HR‐pQCT)] at the tibia and radius in 70 stage II‐IV CKD patients older than 50 years of age; controls belonged to two cohorts of healthy subjects comparable for age and gender (OFELY cohort in women and STRAMBO cohort in men). We examined 46 men and 24 women; 19 patients were diabetic. Mean age was 70.8 ± 8.5 years, mean glomerular filtration rate (GFR) was 34 ± 12 mL/min per 1.73 m2, and mean serum parathyroid hormone (PTH) level was 87 ± 59 pg/mL. Both CKD men and women experienced a moderate but significant trabecular (Tb) impairment, positioning CKD patient values between those of normal and osteopenic controls (e.g., CKD men versus healthy controls: Tb vBMD 172 ± 35 versus 188 ± 34 mg HA/cm3; Tb number 1.75 ± 0.27 versus 1.86 ± 0.26 mm−1, and Tb separation 503 ± 94 versus 465 ± 78 µm; p < .05). Cortical thickness (Ct.Th) in men also was significantly decreased compared with healthy controls (e.g., CKD men versus healthy controls: tibial Ct.Th 1171 ± 331 versus 1288 ± 283 µm; p < .05). In conclusion, this study, using a noninvasive bone‐imaging device, shows for the first time an early impairment of trabecular microarchitecture in stage II‐IV CKD patients. Further longitudinal studies should be performed to validate HR‐pQCT as a tool for predicting the fracture risk in CKD.

Evolution of renal oxygen content measured by BOLD MRI downstream a chronic renal artery stenosis

BACKGROUND A decrease in renal oxygen content can be measured non-invasively by the increase of the R2* value derived from blood oxygen level-dependent magnetic resonance imaging (BOLD MRI). The aim of this study was to test if renal hypoxia occurs in kidneys downstream a chronic and unilateral renal artery stenosis. METHODS Chronic renal ischaemia was induced in rats using a calibrated clip inserted on the right renal artery. R2* was determined, using a multiple recalled gradient-echo sequence, before and once a week after a clip insertion over 4 weeks, in a group of clipped (n = 8) and sham-operated (n = 7) rats. RESULTS At baseline, in stenotic kidneys, R2* was higher in the outer stripe of outer medulla (105 ± 4.6) and the outer medulla (99 ± 2.5) than in the cortex (84 ± 2.5; P < 0.002 for comparison with both areas). R2* was unchanged in the cortex, the outer stripe of outer medulla and the outer medulla in stenotic kidneys, sham-operated kidneys and contralateral kidneys during the 4 weeks. Mean blood pressure was higher in rats with clipped kidney than in sham-operated rats from Day 11 and remained increased thereafter. The renal volume increased progressively in sham-operated kidneys and contralateral kidneys, whereas it slightly decreased in stenotic kidneys. CONCLUSIONS Our study shows that after 4 weeks, no renal hypoxia can be detected in the kidney downstream to a renal artery stenosis, suggesting that atrophy could be induced by other factors.

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.

Hyponatremia secondary to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH): therapeutic decision-making in real-life cases

Despite being the most common electrolyte disturbance encountered in clinical practice, the diagnosis and treatment of hyponatremia (defined as a serum sodium concentration <135 mmol/L) remains far from optimal. This is extremely troubling because not only is hyponatremia associated with increased morbidity, length of hospital stay and hospital resource use, but it has also been shown to be associated with increased mortality. The reasons for this poor management may partly lie in the heterogeneous nature of the disorder; hyponatremia presents with a variety of possible etiologies, differing symptomology and fluid volume status, thereby making its diagnosis potentially complex. In addition, a general lack of awareness of the clinical impact of the disorder, a fear of adverse outcomes through overcorrection of sodium levels, and a lack of effective targeted treatments until recent years, may all have contributed to a reticence to actively treat cases of hyponatremia. There is therefore a clear unmet need to further educate physicians on the pathophysiology, diagnosis and management of this important condition. Through the use of a variety of real-world cases of patients with hyponatremia secondary to the syndrome of inappropriate secretion of antidiuretic hormone—a condition that accounts for approximately one-third of all cases of hyponatremia—this supplement aims to provide a comprehensive overview of the challenges faced in diagnosing and managing hyponatremia. These cases will also help to illustrate how some of the limitations of traditional therapies may be overcome with the use of vasopressin receptor antagonists.

Impact of prior CKD management in a renal care network on early outcomes in incident dialysis patients: a prospective observational study

BackgroundEffective therapeutic strategies are available to prevent adverse outcomes in patients with chronic kidney disease (CKD) but their clinical results are hindered by unplanned implementation. Coordination of care emerges as a suitable way to improve patient outcomes. In this study, we evaluated the effect of planned and coordinated patient management within a dedicated renal care network comparatively to standard renal care delivered in nephrology departments of teaching hospitals.MethodsThis observational matched cohort study included 40 patients with CKD stage 4–5 in the network group as compared with a control group of 120 patients matched for age, sex and diabetic status. Main outcome was a composite endpoint of death from cardiovascular cause and cardiovascular events during the first year after dialysis initiation.ResultsThere was no difference between the two groups neither for the primary outcome (40% vs 41%) nor for the occurrence of death from cardiovascular cause or cardiovascular events. Whereas the proportion of patients requiring at least one hospitalization was identical (83.3% vs 75%), network patients experienced less individual hospitalizations than control patients (2.3±2.0 vs 1.6±1.7) during the year before dialysis start. Patients of the network group had a slower renal function decline (7.7±2.5 vs 4.9±1.1 ml/min/1,73m2 per year; p=0.04).ConclusionsIn this limited series of patients, we were unable to demonstrate a significant impact of the coordinated renal care provided in the network on early cardiovascular events in incident dialysis patients. However, during the predialysis period, there were less hospitalizations and a slower slope of renal function decrease.

Conséquences rénales de l’obésité

The steady increase in the prevalence of obesity contributes to the increase in the prevalence of chronic kidney disease, through renal damages associated with type-2 diabetes and hypertension. Obesity is also an independent risk factor for the kidney, since it is associated with an increased risk of albuminuria and glomerulosclerosis, and worsens the course of chronic kidney disease regardless of the primary renal disease. The existence of a metabolic syndrome, constant in type-2 diabetes, and associated with abdominal obesity, is not the only requirement for renal anomalies of which the translation is a functional hyperfiltration, a clinical microalbuminuria and histologically a glomerulomegaly and glomerulosclerosis. The estimated glomerular filtration rate (GFR) in obese patients is strongly influenced by the weight or indexation to body surface area, and it is logical to take into account the value of non-indexed GFR to assess renal risk and treatment effects, especially if they lead to weight loss. Hypertension is promoted by salt sensitivity, potentially reversible, and overactivity of the renin-angiotensin system (RAS) in part due to adipose tissue. The cytokines secreted by adipose tissue (adipokines), induce sympathetic hyperactivity through leptin, and low-grade inflammatory state that contributes to the development of glomerular sclerosis lesions, especially because a resistance to adiponectin. The treatment relies on weight loss, possibly through bariatric surgery, and antagonists of the RAS.

Coût médical direct des agents stimulant l’érythropoïèse dans le traitement de l’anémie chez le patient insuffisant rénal chronique : revue de la littérature

INTRODUCTION Management of anaemia in chronic renal insufficiency (CRI) represents an important medico-economic challenge because of the great number of patients and the cost of the erythropoiesis-stimulating agent (ESA). The aim of this study was to identify determinants of the costs associated with these treatments in order to choose, with equal efficacy, the most efficient ASE. METHOD A bibliographic research was realised by Medline database interrogation. RESULTS Among the direct medical costs, five studies showed that acquisition of epoetine alfa (EA) compared to darbepoetin alfa (DA) was less expensive. Concerning the costs associated with the route of administration, the subcutaneous injection (SC) of epoetine allowed a gain in costs because of the decrease of doses compared to the intravenous (IV) route. The switch from EA in SC to DA in IV, for hemodialysis patients, was associated with a reduction of the number of injections and with a treatments cost lower by DA than by EA. Costs related to the regimen of administration, notably those related to nursing, medical and pharmaceutical time, were negligible towards those associated to the acquisition of the ASE. Finally, the costs of the therapeutic follow-up and treatment of the adverse effects of the ASE were similar between the EA and the DA. CONCLUSION The costs associated with the prices of acquisition of the ASE, negotiated by the structure of care, represent the most important part of the direct medical costs.

Isolated positive anti-SS-B autoantibodies are not related to clinical features of systemic autoimmune diseases: Results from a routine population survey

Objective To assess in clinical practice the frequency and diagnosis associated with the SS-B-positive/SS-A negative autoantibody profile. Methods We analyzed a one-year consecutive population of 624 patients referred by clinicians to the immunology laboratory to investigate anti-SS-A and/or anti-SS-B autoantibodies, who were detected using luminex technology. Data were analyzed for patients with isolated anti-SS-B autoantibodies. The clinical characteristics and diagnosis of connective tissue diseases (CTD) were retrieved according to the international criteria. Results Among 1173 sera positive for anti-SS-A and/or anti-SS-B autoantibodies from 624 patients, we identified 84 patients (13.5%) that had isolated anti-SS-B. Among the 75 patients positive for anti-SS-B with known clinical data, 15 were diagnosed with a CTD (20%) including 4 systemic lupus erythematosus (5%), 4 rheumatoid arthritis (5%), 2 idiopathic inflammatory myositis (3%), 1 primary Sjögren’s syndrome pSS (1%), 1 systemic sclerosis (1%), 2 undefined CTD (3%), and 1 mixed CTD (1%). Among the 60 other patients, 18 had non-CTD autoimmune diseases and 42 had non-autoimmune diseases. Within the CTD population, the presence of isolated anti-SS-B was not significantly associated to characteristic indicating a specific syndrome. There was no association between diagnosis of CTD and level of anti-SS-B autoantibodies (p = 0.70). Arthralgia was the more frequent sign and encountered in 10 patients (67%), of whom 3 had arthritis. Conclusion The presence of anti-SS-B, without anti-SS-A autoantibodies using luminex technology, was not associated with CTD, especially pSS, in daily clinical practice. Our data suggests that the SS-B serological profile is not contributive for the classification criteria of pSS.

Course of chronic kidney disease in French patients

Background In 1998, a French survey showed that the referral of patients with chronic kidney disease to a nephrologist was delayed, resulting in many emergency initiations of dialysis. In 2009, the ORACLE study aimed to describe the renal course of dialysis patients from their first nephrology visit to their first dialysis session. Methods The ORACLE study was a multicentre retrospective study of all patients who started chronic dialysis. Data were collected at the first nephrology visit and at the first dialysis session. Results In total, 720 patients were included (69 centres). At the first nephrology visit, the mean Cockcroft–Gault (CG) indicator was 31.8 mL/min (22.7 in 1998) and 52.4% of patients (73% in 1998) had a CG <30. The mean time between the first nephrology visit and the first dialysis session was 48 months (35 months in 1998). Conclusion In 2009, most patients were referred a long time before dialysis initiation, which likely allowed them to benefit from the impact of nephrology care on early outcomes when on dialysis. However, 34.2% of the dialysis sessions were still initiated under emergency conditions.