[Prospective assessment of a multidisciplinary meeting dedicated to inflammatory and vascular diseases during pregnancy]. / Évaluation prospective d'une réunion de concertation pluridisciplinaire dédiée aux pathologies inflammatoires et vasculaires lors de la grossesse : la RCP « PREGNANT ¼ au CHU de Bordeaux.

OBJECTIVES: The pluridisciplinary meeting "PREGNANT - Pregnancy and Auto-immunity, Nephropathy, Thrombophilic Disorders" at the university hospital of Bordeaux is dedicated to inflammatory and thrombophilic disorders during pregnancy. The objective of our study was to evaluate the quality of this meeting in terms of: compliance with the mandatory criteria, adequacy with standard care, homogeneity of care, becoming of proposals issued. METHODS: We conducted a prospective observational study including patients whose files were submitted to the meeting from January 2018 to June 2019. RESULTS: In all, 16 meeting were conducted with 152 cases presented. Sixty-two patients were pregnant and 90 were in preconception. The most common reasons for presentation were vasculo-placentary diseases (22.3%), systemic lupus (16.4%), venous thromboembolic diseases (15.1%) and chronic intervillositis of unknown etiology (9.8%). Other reasons were antiphospholipid antibody syndrome and repeated spontaneous miscarriages. The mandatory criteria for multidisciplinary meeting were met. For 89 cases (58.5%), the problem was dictated by recommendations. Decisions made were consistent with recommendations in 89.8% of cases. Among the 63 cases without any published recommendations (41.5%), there was some homogeneity of the proposals. In all, 92.8% of the proposals issued by the meeting were implemented. CONCLUSIONS: Multidisciplinary meeting "PREGNANT" has a prominent locoregional role in the management of patients with autoimmune, inflammatory or thrombophilic disorders in a pregnancy context.

Cardiac troponin-I on diagnosis predicts early death and refractoriness in acquired thrombotic thrombocytopenic purpura. Experience of the French Thrombotic Microangiopathies Reference Center.

BACKGROUND: Cardiac involvement is a major cause of mortality in patients with thrombotic thrombocytopenic purpura (TTP). However, diagnosis remains underestimated and delayed, owing to subclinical injuries. Cardiac troponin-I measurement (cTnI) on admission could improve the early diagnosis of cardiac involvement and have prognostic value. OBJECTIVES: To assess the predictive value of cTnI in patients with TTP for death or refractoriness. PATIENTS/METHODS: The study involved a prospective cohort of adult TTP patients with acquired severe ADAMTS-13 deficiency (< 10%) and included in the registry of the French Reference Center for Thrombotic Microangiopathies. Centralized cTnI measurements were performed on frozen serum on admission. RESULTS: Between January 2003 and December 2011, 133 patients with TTP (mean age, 48 ± 17 years) had available cTnI measurements on admission. Thirty-two patients (24%) had clinical and/or electrocardiogram features. Nineteen (14.3%) had cardiac symptoms, mainly congestive heart failure and myocardial infarction. Electrocardiogram changes, mainly repolarization disorders, were present in 13 cases. An increased cTnI level (> 0.1 µg L(-1) ) was present in 78 patients (59%), of whom 46 (59%) had no clinical cardiac involvement. The main outcomes were death (25%) and refractoriness (17%). Age (P = 0.02) and cTnI level (P = 0.002) showed the greatest impact on survival. A cTnI level of > 0.25 µg L(-1) was the only independent factor in predicting death (odds ratio [OR] 2.87; 95% confidence interval [CI] 1.13-7.22; P = 0.024) and/or refractoriness (OR 3.03; 95% CI 1.27-7.3; P = 0.01). CONCLUSIONS: A CTnI level of > 0.25 µg L(-1) at presentation in patients with TTP appears to be an independent factor associated with a three-fold increase in the risk of death or refractoriness. Therefore, cTnI level should be considered as a prognostic indicator in patients diagnosed with TTP.

Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome.

BACKGROUND: Atypical hemolytic-uremic syndrome is a genetic, life-threatening, chronic disease of complement-mediated thrombotic microangiopathy. Plasma exchange or infusion may transiently maintain normal levels of hematologic measures but does not treat the underlying systemic disease. METHODS: We conducted two prospective phase 2 trials in which patients with atypical hemolytic-uremic syndrome who were 12 years of age or older received eculizumab for 26 weeks and during long-term extension phases. Patients with low platelet counts and renal damage (in trial 1) and those with renal damage but no decrease in the platelet count of more than 25% for at least 8 weeks during plasma exchange or infusion (in trial 2) were recruited. The primary end points included a change in the platelet count (in trial 1) and thrombotic microangiopathy event-free status (no decrease in the platelet count of >25%, no plasma exchange or infusion, and no initiation of dialysis) (in trial 2). RESULTS: A total of 37 patients (17 in trial 1 and 20 in trial 2) received eculizumab for a median of 64 and 62 weeks, respectively. Eculizumab resulted in increases in the platelet count; in trial 1, the mean increase in the count from baseline to week 26 was 73×10(9) per liter (P<0.001). In trial 2, 80% of the patients had thrombotic microangiopathy event-free status. Eculizumab was associated with significant improvement in all secondary end points, with continuous, time-dependent increases in the estimated glomerular filtration rate (GFR). In trial 1, dialysis was discontinued in 4 of 5 patients. Earlier intervention with eculizumab was associated with significantly greater improvement in the estimated GFR. Eculizumab was also associated with improvement in health-related quality of life. No cumulative toxicity of therapy or serious infection-related adverse events, including meningococcal infections, were observed through the extension period. CONCLUSIONS: Eculizumab inhibited complement-mediated thrombotic microangiopathy and was associated with significant time-dependent improvement in renal function in patients with atypical hemolytic-uremic syndrome. (Funded by Alexion Pharmaceuticals; C08-002 ClinicalTrials.gov numbers, NCT00844545 [adults] and NCT00844844 [adolescents]; C08-003 ClinicalTrials.gov numbers, NCT00838513 [adults] and NCT00844428 [adolescents]).

Household transmission of haemolytic uraemic syndrome associated with Escherichia coli O104:H4, south-western France, June 2011.

Following the outbreak of haemolytic uraemic syndrome (HUS) on June 2011 in south-western France, household transmission due to Escherichia coli O104:H4 was suspected for two cases who developed symptoms 9 and 10 days after onset of symptoms of the index case. The analysis of exposures and of the incubation period is in favour of a secondary transmission within the family. Recommendations should be reinforced to prevent person-to-person transmission within households.

[Chronic renal complications induced by lithium]. / Complications rénales chroniques induites par le lithium: revue de la littérature.

INTRODUCTION: After 40 years of use of lithium in the treatment of mood disorders, the renal risks associated with the long-term exposure to lithium are better known. OBJECTIVE: This review is aimed at summarizing the information available in the literature regarding the impact of lithium on renal structure and function, the prevalence of renal abnormalities, the associated risk-factors and the strategy for their identification and management. METHOD: Articles were selected using a Medline search. The keywords were lithium, renal function, kidney, nephrotoxicity, renal insufficiency, side-effects, polyuria, diabetes insipidus and drug monitoring. RESULT: A well-recognized adverse effect of lithium exposure is the occurrence of nephrotic diabetes insipidus (NDI) resulting in polyuria and polydipsia, which occurs in 20% of the patients on long-term lithium treatment. This side-effect is linked to a deficit in urine concentrating ability. Its occurrence is associated with the duration of lithium therapy. Although this effect of lithium is initially functional and may disappear if the treatment is rapidly stopped, it may become structural and permanent over time. The decision to stop lithium or to treat the NDI with amiloride is mainly based upon its functional impact. DISCUSSION: A debate has been ongoing for decades regarding whether or not the long-term use of lithium may cause slowly progressive renal failure. According to the recent literature, progressive renal failure occurs in approximately 20% of the patients on long-term lithium treatment, among whom a few develop severe renal insufficiency due to lithium (possibly in conjunction with other somatic factors) in the form of interstitial nephritis. However, there is an increasing number of reports of patients requiring dialysis after long-term exposure to lithium. CONCLUSION: Current recommended strategies for minimising the renal side effects of lithium include: avoiding acute episodes of renal toxicity; monitoring serum lithium concentrations in order to achieve optimal efficacy at the lowest possible concentrations; monitoring serum creatinine levels at least on a yearly basis, with discontinuation of lithium use, discussion with a nephrologist if creatinine clearance decreases below 60 ml/mn; and the possible application of lithium into single daily dose.

MR imaging of nephropathies.

Acute and chronic nephropathies are responsible for morphologic and functional renal changes. However, radiologic techniques currently play a minor role in imaging of parenchymal nephropathies in native or transplanted kidneys. From a morphologic point of view, three-dimensional magnetic resonance (MR) volumetric biomarkers of kidney function, such as renal and cortical volumes or cystic volume, in polycystic kidney diseases play a growing role in nephrologic practice. From a functional point of view, if scintigraphic techniques remain the major sources of renal performance assessment, new MR imaging systems and specific MR contrast agents may soon provide significant developments in the evaluation of renal performance (glomerular filtration rate measurement), in the search for prognostic factors (hypoxia, inflammation, cell viability, degree of tubular function, and interstitial fibrosis), and for monitoring new cell therapies. New developments that have provided higher signal-to-noise ratio and higher spatial and/or temporal resolutions have the potential to direct new opportunities for obtaining morphologic and functional information on tissue characteristics that are relevant for various renal diseases with respect to diagnosis, prognosis, and treatment follow-up.

Procalcitonin: a new marker of inflammation in haemodialysis patients?

BACKGROUND: Although procalcitonin (PCT) has been described as a new marker of infection and inflammation, it has not been extensively studied in dialysis patients. METHODS: We measured plasma PCT levels in 62 patients on maintenance haemodialysis (30 M/32 F, age 61.8+/-17.1 years, on dialysis for 75+/-93 months, 12 h/week, with a Kt/V of 1.53+/-0.31, high-flux membrane being used in 25 patients and low-flux in 37 patients, without reuse). PCT levels were compared with other markers of inflammation and nutritional status, including C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), leukocytes, urea, creatinine, albumin, prealbumin, normalized protein catabolic rate (nPCR), haemoglobin (Hb), and epoetin (Epo) doses. Patients were divided into different groups according to their infectious and vascular status. RESULTS: PCT plasma levels before dialysis were 0.69+/-0.81 ng/ml. Fifty-seven per cent of PCT values were higher than the upper normal limit of 0.5 ng/ml. CRP and PCT concentrations were high in patients with a current infection, while IL-6 values were elevated in all patients regardless of infection status. Plasma CRP concentrations before dialysis were 21.2+/-31.4 mg/l, and 70% of these values were higher than the upper normal limit. CRP, PCT, IL-6, and fibrinogen were positively correlated with each other and were all negatively correlated with albumin. Prealbumin was negatively correlated with CRP and IL-6. In the 43 patients treated with Epo, haemoglobin was negatively correlated with IL-6 and Epo doses, while Epo doses were positively correlated with IL-6 but not with CRP or PCT. The 23 patients with both elevated PCT and CRP plasma levels had the lowest Hb, albumin, and prealbumin concentrations, and the highest fibrinogen concentrations and Epo doses. CONCLUSION: PCT in haemodialysis patients is positively correlated with currently used markers of inflammation such as CRP and fibrinogen, and negatively correlated with markers of nutritional status such as albumin. The concomitant elevations in PCT and CRP could be more sensitive in the evaluation of inflammation than each marker separately.

Impact of high-flux/high-efficiency dialysis on folate and homocysteine metabolism.

High-flux/high-efficiency (HF/HE) dialysis may have detrimental effects on micro-nutrients and water-soluble vitamins, such as vitamin B6, whose levels are lowered. Folate deficiency may increase cardiovascular risk through an increase in homocysteine (Hcy) serum levels. We therefore investigated the effects of dialysis with a high-flux (HF) membrane on folate and Hcy metabolism. Twelve patients without any folate supplementation, receiving dialysis with a low-flux membrane prior to the study (TO), were switched to dialysis using a HF triacetate membrane for four months (T1, T2, T3, T4) and received an oral daily folate supplementation during the two last months (T3, T4). Mean predialysis plasma folate levels fell dramatically after one month of HF dialysis (T1) and remained significantly lower than the initial level (p<0.05) at T2. Hcy concentrations were high in all patients at TO (mean 47.3 +/- 17.6 microM, normal range 5 to 15 microM). They did not change during the first two months of the study but dropped steeply after the beginning of oral folate supplementation. Folate supplementation should be used in HF/HE dialysis to avoid folate depletion. The combination of folate supplementation and HF/HE may lower Hcy levels and reduce cardiovascular morbidity and mortality in these patients.

Determinants of arterial compliance in patients treated by hemodialysis.

BACKGROUND: Cardiovascular disease is the principal cause of morbidity and mortality among hemodialysis patients. Several studies have demonstrated the importance of a reduction in arterial compliance in the development of cardiovascular complications, reflecting the interaction of functional and structural alterations of the peripheral arterial system and left ventricle. The aim of the present study was to demonstrate that arterial compliance, evaluated by automated recording of the QKd interval, was lower in hemodialysis patients than in normal subjects. A secondary objective of the study was to assess the influence of several factors, including calcium-phosphorus parameters, on decreased arterial compliance in these patients. PATIENTS AND METHODS: Arterial compliance was evaluated in 24 chronic hemodialysis patients who had normal (n = 12) or high blood pressure (n = 12), using a method of measuring systolic wave velocity by automated recording of the QKd interval. This interval corresponds to the time (in ms) between the onset of the electrocardiogram QRS complex (Q) and the Korotkoff (K) sound at diastolic pressure (d) heard over the brachial artery during blood pressure measurement. The analysis was performed in comparison with reference values obtained in a population with normal renal function. The other parameters determined were: age, duration of chronic renal failure, duration of hemodialysis therapy, left ventricular mass, vascular calcification score, serum total and ionized calcium, phosphorus, parathyroid hormone, calcidiol, calcitriol, and blood concentration of hemoglobin. RESULTS: The arterial stiffness of all the patients was increased significantly (p < 0.001) compared to reference values obtained from subjects without renal failure, the average age, height, and blood pressure of whom were similar to those of the patients. Multivariate analysis demonstrated a positive relationship among the QKd interval, serum total calcium, and the duration of hemodialysis. This suggested that arterial wall elastic properties were dependent not only on hypertension and constraints of pressure, but that they were also influenced by calcium and phosphorus metabolism and the duration of renal substitution therapy. CONCLUSIONS: Arterial compliance, evaluated by the ambulatory method of QKd measurement, is reduced in chronic hemodialysis patients, and is inversely correlated with serum calcium concentration and dependent on the previous duration of hemodialysis therapy.