Low parathyroid hormone status induced by high dialysate calcium is an independent risk factor for cardiovascular death in hemodialysis patients

Here we studied a possible association between low parathyroid hormone (PTH) status and mortality in incident patients undergoing hemodialysis . A total of 1983 patients were included at baseline and prospectively followed for 24 months. Patients were classified according to their Kidney Disease: Improving Global Outcomes PTH status at baseline and at 12 months, and mortality evaluated at 12 to 24 months using adjusted Cox analysis. Factors potentially involved in PTH status variability between baseline and 12 months were analyzed. A decrease in serum PTH from normal or high to low values between baseline and 12 months was associated with significantly increased cardiovascular mortality at 12 to 24 months (hazard ratio, 2.03; 95% confidence interval, 1.22–3.36). For patients with high or normal baseline PTH levels, the main independent factor at 6 months for a decrease to low PTH levels at 12 months was high dialysate calcium (1.75 mmol/L), whereas prescription of non–calcium-based phosphate binders was associated with a lower risk of PTH decrease. In the high cardiovascular (CV) mortality risk subgroup of patients who acquired a low PTH status at 12 months, the main independent factor at 12 months associated with significant 12- to 24-month CV mortality was high dialysate calcium (odds ratio, 5.44; 95% CI, 2.52–11.75). Thus, patients with a serum PTH decrease to low values after 1 year of hemodialysis treatment are at high risk of short-term CV death. High dialysate calcium was an important contributor to PTH oversuppression, and continued use was associated with increased CV mortality

MAIT cells altered phenotype and cytotoxicity in lupus patients are linked to renal disease severity and outcome

IntroductionSystemic lupus erythematosus (SLE) is an autoimmune disease in which circulating immune complexes can cause different types of glomerulonephritis, according to immune deposits and to the type of glomerular cell injury. Proliferative lesions represent the most severe form of lupus nephritis (LN) and often lead to kidney failure and death. Mucosal-associated invariant T (MAIT) cells are a subset of innate-like T cells that recognize microbial-derived ligands from the riboflavin synthesis pathway. Although abundant in peripheral blood, MAIT cells are enriched in mucosal and inflamed tissues. While previous studies have reported concordant results concerning lower MAIT cell frequencies in the blood of SLE patients, no information is known about MAIT cell function and LN severity and outcome.MethodsIn the current study, we analyzed the baseline phenotype and function of peripheral blood MAIT cells by flow cytometry in 26 patients with LN and in a control group of 16 healthy individuals.ResultsWe observe that MAIT cell frequencies are markedly reduced in blood of LN patients. MAIT cells from patients have an altered phenotype in terms of migration, proliferation and differentiation markers, notably in most severe forms of LN. Frequencies of PMA/ionomycin stimulated MAIT cells secreting effector molecules, such as proinflammatory IL-17 and cytotoxic protein granzyme B, are higher in LN patients. Patients undergoing a complete renal remission after immunosuppressive therapy had higher MAIT cell frequency, lower expression of proliferation marker Ki-67 and granzyme B (GzB) at inclusion. Remarkably, GzB production defines a predictive model for complete remission.DiscussionWe report here that blood MAIT cells display proinflammatory and cytotoxic function in severe lupus nephritis which may play a pathogenesis role, but without association with systemic lupus activity. Finally, low cytotoxic profile of MAIT cells may represent a promising prognostic factor of lupus nephritis remission one year after induction therapy

Two Distinct Pathways Leading to Nuclear Apoptosis

Apaf-1−/− or caspase-3−/− cells treated with a variety of apoptosis inducers manifest apoptosis-associated alterations including the translocation of apoptosis-inducing factor (AIF) from mitochondria to nuclei, large scale DNA fragmentation, and initial chromatin condensation (stage I). However, when compared with normal control cells, Apaf-1−/− or caspase-3−/− cells fail to exhibit oligonucleosomal chromatin digestion and a more advanced pattern of chromatin condensation (stage II). Microinjection of such cells with recombinant AIF only causes peripheral chromatin condensation (stage I), whereas microinjection with activated caspase-3 or its downstream target caspase-activated DNAse (CAD) causes a more pronounced type of chromatin condensation (stage II). Similarly, when added to purified HeLa nuclei, AIF causes stage I chromatin condensation and large-scale DNA fragmentation, whereas CAD induces stage II chromatin condensation and oligonucleosomal DNA degradation. Furthermore, in a cell-free system, concomitant neutralization of AIF and CAD is required to suppress the nuclear DNA loss caused by cytoplasmic extracts from apoptotic wild-type cells. In contrast, AIF depletion alone suffices to suppress the nuclear DNA loss contained in extracts from apoptotic Apaf-1−/− or caspase-3−/− cells. As a result, at least two redundant parallel pathways may lead to chromatin processing during apoptosis. One of these pathways involves Apaf-1 and caspases, as well as CAD, and leads to oligonucleosomal DNA fragmentation and advanced chromatin condensation. The other pathway, which is caspase-independent, involves AIF and leads to large-scale DNA fragmentation and peripheral chromatin condensation

An above-barrier narrow resonance in F-15

Intense and purified radioactive beam of post-accelerated O-14 was used to study the low-lying states in the unbound F-15 nucleus. Exploiting resonant elastic scattering in inverse kinematics with a thick target, the second excited state, a resonance at E-R = 4.757(6)(10) MeV with a width of Gamma = 36(5)(14) keV was measured for the first time with high precision. The structure of this narrow above-barrier state in a nucleus located two neutrons beyond the proton drip line was investigated using the Gamow Shell Model in the coupled channel representation with a C-12 core and three valence protons. It is found that it is an almost pure wave function of two quasi-bound protons in the 2s(1/2) shell. (C) 2016 The Authors. Published by Elsevier B.V

L infiltrat cellulaire interstitiel rénal est-il un facteur pronostique rénal chez les patients infectés par le VIH ?

La valeur pronostique de l infiltrat cellulaire interstitiel rénal parmi les patients infectés par le VIH atteints de maladie rénale n est pas clairement établie. Ainsi, nous avons rétrospectivement étudié une cohorte parisienne (Saint-Louis et Bichat) de 88 patients consécutifs infectés par le VIH ayant subi une biopsie rénale entre janvier 2000 et juillet 2010, ère des trithérapies antirétrovirales. Toutes les biopsies rénales ont été relues en aveugle des conclusions précédentes. L infiltrat interstitiel a été évalué selon la surface occupée sur chaque biopsie. Parmi 88 patients, dont 78 avec suivi, 38.6% étaient atteints d HIVAN, 27.2% de néphropathies tubulo-interstitielles et 22.7% de glomérulopathies autres. Plus la surface d infiltrat était élevée, plus la créatininémie était haute et le DFG bas, initialement et à 1 an. L épuration extra-rénale a été débutée chez 27 patients (35%), en médiane à 13 mois. Après ajustement sur l âge, le sexe, l origine ethnique, le taux de CD4, la charge virale VIH et la prise de traitements antirétroviraux dans un modèle de Cox multivarié, une surface élevée d infiltrat interstitiel cellulaire rénal >50% (p<0.001; HR= 7.19; CI= [2.50-24.95]) et un DFG initial bas <15mL /min (p=0.002; HR= 5.06; CI= [2.04-14.27]) ont été identifiés comme facteurs prédictifs de mauvaise survie rénale, de façon significative. L infiltrat cellulaire interstitiel rénal est donc un facteur indépendant de mauvaise survie rénale parmi les patients infectés par le VIH atteints d une maladie rénale. Cette découverte ouvre des perspectives thérapeutiques ciblant les facteurs déterminants l infiltrat, afin d améliorer la survie rénale de ces patients.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocSudocFranceF

Etude des marqueurs d activation des basophiles dans le lupus érythémateux systémique avec atteinte rénale

PARIS7-Xavier Bichat (751182101) / SudocSudocFranceF

Suivi à long terme des néphropathies liées au antiphospholipides dans le cadre du lupus

PARIS7-Xavier Bichat (751182101) / SudocSudocFranceF