[Prevalence of iron deficiency in patients with non-dialysis chronic kidney disease: The CARENFER national, multicentre, observational study]. / Prévalence de la carence martiale dans une population de patients insuffisants rénaux chroniques non dialysés : étude nationale multicentrique observationnelle CARENFER.

INTRODUCTION: Iron deficiency is common and associated with worse outcomes in patients with non-dialysis chronic kidney disease. We performed a national, multicentre, observational and transversal study to assess the prevalence of iron deficiency as well as current iron deficiency screening practices in this population. PATIENTS AND METHODS: A total of 25 nephrology centres in France participated in the study. All adult non-dialysis chronic kidney disease patients who met the inclusion (GFR>15mL/min/1.73m2) and exclusion criteria and provided consent were systematically recruited over a 4-week inclusion period. Investigators were asked to perform a blood test (hemoglobin concentration, serum iron, serum ferritin and transferrin saturation) and to complete a questionnaire about their iron status monitoring practices. The primary objective was to assess the prevalence of iron deficiency (serum ferritin<100µg/L and/or transferrin saturation<20%). Secondary objectives were to evaluate the prevalence of absolute iron deficiency (serum ferritin<100µg/L and transferrin saturation<20%) and functional iron deficiency (serum ferritin≥100µg/L and transferrin saturation<20%), the prevalence of iron deficiency according to haemoglobin concentration and chronic kidney disease stage, the proportion of centres that perform routine evaluation of iron status and the number of patients receiving iron supplementation. RESULTS: A total of 1211 patients with non-dialysis chronic kidney disease were included in the analysis. The overall prevalence of iron deficiency was 47.1%. The rates of absolute iron deficiency and functional iron deficiency and anaemia were 13.4% and 17.1%, respectively. Among the 25 participating centres, 12 reported routine assessment of iron status in non-dialysis chronic kidney disease patients. CONCLUSION: In this observational study, a high prevalence of iron deficiency was observed among non-dialysis chronic kidney disease patients. Less than half of participating centres reported routine assessment of iron status.

Balancing benefits and risks of glucocorticoids in rheumatic diseases and other inflammatory joint disorders: new insights from emerging data. An expert consensus paper from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO).

PURPOSE: This consensus review article considers the question of whether glucocorticoid (GC) therapy is still relevant in the treatment of rheumatic diseases, with a particular focus on rheumatoid arthritis (RA), and whether its side effects can be adequately managed. Recent basic and clinical research on the molecular, cellular and clinical effects of GCs have considerably advanced our knowledge in this field. An overview of the subject seems appropriate. METHODS: This review is the result of a multidisciplinary expert working group, organised by European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis. The recent literature was surveyed and the salient evidence synthetized. RESULTS: The pathophysiological basis of RA (and other inflammatory rheumatic diseases) now strongly implicates the adaptive immune system in addition to innate mechanisms. The molecular effect of GCs and differential GC sensitivity is better understood, although exploiting this knowledge is still in its infancy. The newer treatment strategies of early and aggressive control of RA have gr eatly improved clinical outcomes, but improvements are still possible. Newer targeted anti-inflammatory drugs have made an important impact, yet they too are associated with numerous side effects. DISCUSSION: Short durations of moderate doses of GCs are generally well tolerated and have a positive benefit/risk ratio. Patients should be assessed for fracture risk and bone preserving agents and be prescribed calcium and vitamin D supplementation. CONCLUSIONS: Within a strategy of a disease modifying approach to inflammatory disease, combination therapy including a GC is effective approach.

Iron deficiency anaemia.

Anaemia affects roughly a third of the world's population; half the cases are due to iron deficiency. It is a major and global public health problem that affects maternal and child mortality, physical performance, and referral to health-care professionals. Children aged 0-5 years, women of childbearing age, and pregnant women are particularly at risk. Several chronic diseases are frequently associated with iron deficiency anaemia--notably chronic kidney disease, chronic heart failure, cancer, and inflammatory bowel disease. Measurement of serum ferritin, transferrin saturation, serum soluble transferrin receptors, and the serum soluble transferrin receptors-ferritin index are more accurate than classic red cell indices in the diagnosis of iron deficiency anaemia. In addition to the search for and treatment of the cause of iron deficiency, treatment strategies encompass prevention, including food fortification and iron supplementation. Oral iron is usually recommended as first-line therapy, but the most recent intravenous iron formulations, which have been available for nearly a decade, seem to replenish iron stores safely and effectively. Hepcidin has a key role in iron homoeostasis and could be a future diagnostic and therapeutic target. In this Seminar, we discuss the clinical presentation, epidemiology, pathophysiology, diagnosis, and acute management of iron deficiency anaemia, and outstanding research questions for treatment.

Guidelines on the diagnosis and treatment of iron deficiency across indications: a systematic review.

BACKGROUND: Guidelines on the diagnosis and treatment of iron deficiency (ID) vary widely across indications. OBJECTIVE: We reviewed all available guidelines on the management of ID worldwide. DESIGN: A literature search was conducted in PubMed, Cochrane, and EMBASE and in main professional association websites, limited to documents published between 1 January 2004 and 30 June 2014. RESULTS: Of 127 guidelines identified, 29 were selected, involving 29 professional associations and issued from the United States (n = 8), Europe (n = 6), Britain (n = 4), Canada (n = 3), international organizations (n = 2), France (n = 2), Poland (n = 1), Australia (n = 1), Mexico (n = 1), and Japan (n = 1). A total of 22 and 27 guidelines provided recommendations on diagnosis and treatment of ID, respectively. To define ID, all guidelines recommended a concentration for serum ferritin. One-half of them (10 of 22) proposed transferrin saturation (TSAT) as an alternative or complementary diagnostic test. To treat ID, most of the guidelines (18 of 27) recommended preferentially the oral route if possible, particularly in children and in women in the pre- or postpregnancy period. Iron supplementation should be administered intravenously according to 13 of 27 guidelines, particularly in patients with chronic kidney disease (CKD) (n = 7) and chemotherapy-induced anemia (n = 5). Treatment targets for ID included an increase in hemoglobin concentrations to 10-12 g/dL or normalization (n = 8) and serum ferritin >100 µg/L (n = 7) or 200 µg/L (n = 4). For the latter, in some situations, such as CKD, ferritin concentrations should not exceed 500 µg/L (n = 5) or 800 µg/L (n = 5). Only 9 guidelines recommended TSAT as a target, proposing various thresholds ranging from 20% to 50%. CONCLUSIONS: It appears that for the diagnosis of ID, a cutoff of 100 µg/L for serum ferritin concentration should be considered in most conditions and 20% for TSAT, except in particular situations, including young healthy women with heavy menstrual flow. New indications of intravenous iron supplementation are emerging.

Translation strategy for the qualification of drug-induced vascular injury biomarkers.

Drug-induced vascular injury (DIVI) is a common preclinical toxicity usually characterized by hemorrhage, vascular endothelial and smooth muscle damage, and inflammation. DIVI findings can cause delays or termination of drug candidates due to low safety margins. The situation is complicated by the absence of sensitive, noninvasive biomarkers for monitoring vascular injury and the uncertain relevance to humans. The Safer And Faster Evidence-based Translation (SAFE-T) consortium is a public-private partnership funded within the European Commission's Innovative Medicines Initiative (IMI) aiming to accelerate drug development by qualifying biomarkers for drug-induced organ injuries, including DIVI. The group is using patients with vascular diseases that have key histomorphologic features (endothelial damage, smooth muscle damage, and inflammation) in common with those observed in DIVI, and has selected candidate biomarkers associated with these features. Studied populations include healthy volunteers, patients with spontaneous vasculitides and other vascular disorders. Initial results from studies with healthy volunteers and patients with vasculitides show that a panel of biomarkers can successfully discriminate the population groups. The SAFE-T group plans to seek endorsement from health authorities (European Medicines Agency and Food and Drug Administration) to qualify the biomarkers for use in regulatory decision-making processes.

Biotherapies in Behçet's disease.

Behçet's disease (BD) is a systemic large-vessel vasculitis characterized by a wide clinical spectrum including recurrent oral and genital ulcerations, uveitis, vascular, neurological, articular, renal and gastrointestinal manifestations. Therapeutic management of BD depends on the clinical presentation and organ involved. Although colchicine, nonsteroidal antiinflammatory agents and topical treatments with corticosteroids are often sufficient for mucocutaneous and joint involvements, more aggressive approach with immunosuppressive agents is warranted for severe manifestations such as posterior uveitis, retinal vasculitis, vascular, and neurological and gastrointestinal involvements. However, some patients still have refractory disease, relapse, sight threatening eye disease, or irreversible organ damage. Recent improvements in the understanding of the pathogenic mechanisms have led to the identification of potential targets and future biological therapies for BD. In contrast to current non-specific immunosuppressive agents, the emergence of biotherapies provides the possibility of interfering with specific pathogenic pathways. Novel targeted biotherapies might be used in the future for BD.

Low 25-hydroxyvitamin D serum levels correlate with the presence of extra-hepatic manifestations in chronic hepatitis C virus infection.

OBJECTIVE: Chronic HCV infection is associated with extra-hepatic manifestations. Recent studies have suggested an immunomodulatory role for vitamin D during HCV infection. We investigated the association between serum vitamin D status and the presence of HCV extra-hepatic manifestations. METHODS: 25(OH)D serum levels were assessed in 94 HCV(+)RNA(+) patients [including 48 patients with mixed cryoglobulinaemia (MC) vasculitis]. Correlations between serum 25(OH)D levels and the presence of extra-hepatic manifestations of HCV infection were analysed. RESULTS: Overall, 84 of 94 patients (89%) had hypovitaminosis D (≤30 ng/ml). Patients with vitamin D deficiency vs insufficiency vs sufficiency more frequently had systemic vasculitis (P = 0.02), in particular purpura (P = 0.006), detectable MC (P = 0.008) and low C4 serum levels (P = 0.006). Serum levels of 25(OH)D were also correlated with cryoglobulin and C4 levels and with marginal zone B cells and regulatory T cells. In multivariate analysis, the presence of MC and systemic vasculitis remained independently associated with low 25(OH)D levels. CONCLUSION: In chronic HCV infection, low 25(OH)D levels correlate with the presence of mixed cryoglobulinaemia and systemic vasculitis in chronic HCV infection. These findings suggest the potential multifaceted benefits of vitamin D supplementation in HCV-infected patients with extra-hepatic manifestations, but interventional studies are needed to confirm these data.

Potentiation of fluindione or warfarin by dexamethasone in multiple myeloma and AL amyloidosis.

OBJECTIVES: Patients with primary systemic (AL) amyloidosis or multiple myeloma are frequently treated with cyclic dexamethasone (DXM) courses and often require oral anticoagulants. We previously reported a strong potentiation of oral anticoagulants with intravenous methylprednisolone and observed a similar potentiation with DXM in 3 patients, which led us to prospectively investigate the interaction between DXM and oral anticoagulants. METHODS: Nine patients with multiple myeloma (n=6) or AL amyloidosis (n=3), including 6 prospective patients, taking fluindione (n=8) or warfarin (n=1), were studied for a total of 10 cycles. DXM (40 mg/day for 4 days every 28 days) was administered alone (n=4) or with melphalan (n=5). One patient was studied for 2 consecutive cycles after a moderate increase in the international normalized ratio (INR) during the first course of DXM. International normalized ratio (INR) was measured serially during DXM administration. Plasma oral anticoagulant concentrations were measured for 5 cycles. RESULTS: The mean INR increased from 2.75 (range: 1.80-3.6) at baseline to 5.22 (3.09-7.07) after DXM. Oral anticoagulants were transiently stopped during 8 cycles and 1 mg oral vitamin K was given during 2. No serious bleeding was observed. Plasma oral anticoagulant concentrations increased after DXM administration. In controls receiving DXM without oral anticoagulants, DXM alone did not increase prothrombin time. CONCLUSION: High dose DXM can potentiate oral anticoagulants and elevate INR substantially. INR should therefore be monitored repeatedly during concomitant administration of these 2 drugs to allow individual adaptation of oral anticoagulant doses.