Rituximab-associated interstitial lung disease in fibrillary glomerulonephritis.

Rituximab (RTX) is a chimeric monoclonal antibody against CD20+ B cells increasingly used to treat kidney disorders. RTX-induced pulmonary disease has been reported in patients treated for haematological disorders, and a few cases have been observed in patients with underlying rheumatological conditions. We report a case of non-infectious interstitial pneumonitis associated with RTX use in a 49-year-old patient with primary (fibrillary) glomerulonephritis.

Eplerenone enhances cardioprotective effects of standard heart failure therapy through matricellular proteins in hypertensive heart failure.

Aims: The addition of an aldosterone receptor antagonist on top of current optimal therapy (based on angiotensin II inhibition) has demonstrated an important clinical benefit in heart failure patients with systolic dysfunction. Whether this finding also applies to heart failure patients with preserved systolic function is unknown. Therefore, we have studied the effect of adding eplerenone to standard pharmacological heart failure therapy (angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and diuretic and β-blocker) in the progression of heart failure in spontaneously hypertensive heart failure (SHHF) rats.

Unilateral ureteral obstruction: beyond obstruction.

Unilateral ureteral obstruction is a popular experimental model of renal injury. However, the study of the kidney response to urinary tract obstruction is only one of several advantages of this model. Unilateral ureteral obstruction causes subacute renal injury characterized by tubular cell injury, interstitial inflammation and fibrosis.

Osteoprotegerin in exosome-like vesicles from human cultured tubular cells and urine.

Urinary exosomes have been proposed as potential diagnostic tools. TNF superfamily cytokines and receptors may be present in exosomes and are expressed by proximal tubular cells. We have now studied the expression of selected TNF superfamily proteins in exosome-like vesicles from cultured human proximal tubular cells and human urine and have identified additional proteins in these vesicles by LC-MS/MS proteomics.

TWEAK transactivation of the epidermal growth factor receptor mediates renal inflammation.

TWEAK, a member of the TNF superfamily, binds to the Fn14 receptor, eliciting biological responses. EGFR signalling is involved in experimental renal injury. Our aim was to investigate the relationship between TWEAK and EGFR in the kidney.

Questionable reversal of anticoagulation in the therapeutic management of cerebral haemorrhage associated with vitamin K antagonists.

Reversal of anticoagulation is recommended to correct the international normalised ratio (INR) for patients with intracranial haemorrhage (ICH) associated with vitamin K antagonists (VKA). However, the validity of such treatment is debated. We sought to identify, prospectively, the prognostic effect of VKA-ICH treatment in a cohort of patients (n=71; median age 78 years, range 20-89; 52% males).

Fn14 in podocytes and proteinuric kidney disease.

Non-proliferative proteinuric diseases are the most common primary glomerular disorders causing end-stage renal disease. These disorders may associate low level glomerular inflammation and podocyte expression of inflammatory mediators. However, the factors regulating podocyte expression of inflammatory mediators in vivo in non-immune disorders are poorly understood.

Bisphenol a in chronic kidney disease.

Phenols are uremic toxins of intestinal origin formed by bacteria during protein metabolism. Of these molecules, p-cresol is the most studied and has been associated with renal function impairment and vascular damage. Bisphenol A (BPA) is a molecule with structural similarity with phenols found in plastic food and beverage containers as well as in some dialyzers.

Calcineurin inhibitors recruit protein kinases JAK2 and JNK, TLR signaling and the UPR to activate NF-κB-mediated inflammatory responses in kidney tubular cells.

The calcineurin inhibitors (CNIs) cyclosporine (CsA) and tacrolimus are key drugs in current immunosuppressive regimes for solid organ transplantation. However, they are nephrotoxic and promote death and profibrotic responses in tubular cells. Moreover, renal inflammation is observed in CNI nephrotoxicity but the mechanisms are poorly understood.

Connective tissue growth factor is a new ligand of epidermal growth factor receptor.

Chronic kidney disease is reaching epidemic proportions worldwide and there is no effective treatment. Connective tissue growth factor (CCN2) has been suggested as a risk biomarker and a potential therapeutic target for renal diseases, but its specific receptor has not been identified. Epidermal growth factor receptor (EGFR) participates in kidney damage, but whether CCN2 activates the EGFR pathway is unknown.

Endovascular treatment of distal internal carotid artery occlusions with retrievable stents.

Background: Acute stroke due to distal intracranial internal carotid artery (ICA) occlusion has a poor natural history. Outcome in patients who receive intravenous tissue plasminogen activator (tPA) is also unsatisfactory. The objective of this study is to evaluate the effectiveness and safety of endovascular treatment with retrievable stents in these patients.

Prevalence of protein-energy wasting syndrome and its association with mortality in haemodialysis patients in a centre in Spain.

Introduction: Malnutrition has been described in patients with chronic kidney disease as well as its association with cardiovascular risk and mortality in haemodialysis patients. Recently, the new term "protein energy wasting" has been proposed with new diagnostic criteria (biochemical and anthropometric markers) for early identification of patients at risk for protein energy wasting and mortality. The aim of this study was to examine the prevalence, evolution over time and prognostic significance of PEW in a Spanish dialysis centre for the first time in Spain.

Importance of cerebral artery recanalization in patients with stroke with and without neurological improvement after intravenous thrombolysis.

Background And Purpose: Recanalization status after intravenous thrombolysis (IVT) in patients with ischemic stroke is a reference point to proceed with a rescue reperfusion intervention, although early neurological improvement (NI) may preclude endovascular procedures. We aimed to evaluate the importance of restoration of blood flow at the arterial occlusion site in subgroups of patients with stroke stratified by early NI after IVT.

Methods: The following patients were recruited from the Safe Implementation of Treatment in Stroke-International Stroke Thrombolysis Register: (1) with baseline vessel occlusion documented by computed tomographic (CT) or magnetic resonance (MR) angiography and follow-up angioimaging between 22 and 36 hours after IVT available; and (2) with dense cerebral artery sign on admission CT scan and results of follow-up CT reported.

Gene Deficiency in Activating Fcγ Receptors Influences the Macrophage Phenotypic Balance and Reduces Atherosclerosis in Mice.

Immunity contributes to arterial inflammation during atherosclerosis. Oxidized low-density lipoproteins induce an autoimmune response characterized by specific antibodies and immune complexes in atherosclerotic patients. We hypothesize that specific Fcγ receptors for IgG constant region participate in atherogenesis by regulating the inflammatory state of lesional macrophages.

Macrophages and recently identified forms of cell death.

Recent advances in cell death biology have uncovered an ever increasing range of cell death forms. Macrophages have a bidirectional relationship with cell death that modulates the immune response. Thus, macrophages engulf apoptotic cells and secrete cytokines that may promote cell death in parenchymal cells.

TNF-related weak inducer of apoptosis (TWEAK) promotes kidney fibrosis and Ras-dependent proliferation of cultured renal fibroblast.

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) regulates apoptosis, proliferation and inflammation in renal epithelial cells and plays a role in acute kidney injury. However, there is little information on the chronic effects of TWEAK. We hypothesized that TWEAK may influence renal fibrosis and regulate kidney fibroblast biology, in part, through Ras pathway.

Proteomic analysis of intraluminal thrombus highlights complement activation in human abdominal aortic aneurysms.

Objective: To identify proteins related to intraluminal thrombus biological activities that could help to find novel pathological mechanisms and therapeutic targets for human abdominal aortic aneurysm (AAA).

Approach And Results: Tissue-conditioned media from patients with AAA were analyzed by a mass spectrometry-based strategy using liquid chromatography coupled to tandem mass spectrometry. Global pathway analysis by Ingenuity software highlighted the presence of several circulating proteins, among them were proteins from the complement system.

Correction of hypocalcemia allows optimal recruitment of FGF-23-dependent phosphaturic mechanisms in acute hyperphosphatemia post-phosphate enema.

Both parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) are phosphaturic hormones. These hormones should increase in response to phosphate excess. However, they also regulate serum calcium; PTH increases serum calcium concentration and FGF23 suppresses renal production of calcitriol, favoring hypocalcemia.

[Endovascular treatment in acute ischaemic stroke. A stroke care plan for the region of Madrid].

Introduction: Endovascular therapies (intra-arterial thrombolysis and mechanical thrombectomy) after acute ischaemic stroke are being implemented in the clinical setting even as they are still being researched. Since we lack sufficient data to establish accurate evidence-based recommendations for use of these treatments, we must develop clinical protocols based on current knowledge and carefully monitor all procedures.

Development: After review of the literature and holding work sessions to reach a consensus among experts, we developed a clinical protocol including indications and contraindications for endovascular therapies use in acute ischaemic stroke.

The C-terminal module IV of connective tissue growth factor is a novel immune modulator of the Th17 response.

Connective tissue growth factor (CTGF/CCN2) is a matricellular protein susceptible to proteolytic degradation. CCN2 levels have been suggested as a potential risk biomarker in several chronic diseases. In body fluids, CCN2 full-length and its degradation fragments can be found; however, their in vivo effects are far from being elucidated.

Peptide inhibitor of NF-κB translocation ameliorates experimental atherosclerosis.

Atherosclerosis is a chronic inflammatory disease of the arterial wall. NF-κB is a major regulator of inflammation that controls the expression of many genes involved in atherogenesis. Activated NF-κB was detected in human atherosclerotic plaques, and modulation of NF-κB inflammatory activity limits disease progression in mice.

Unraveling biomarkers of abdominal aortic aneurisms by iTRAQ analysis of depleted plasma.

Abdominal aortic aneurysm (AAA) is a significant health problem in Western countries. The diameter of AAA is a surrogate marker of its growth rate that reflects the magnitude of the degenerative process in the vascular wall, although most AAAs show discontinuous growth patterns and alternate periods of stability and nongrowth with periods of acute expansion and occasionally ruptures. Thus, the identification of biomarkers of AAA in plasma could aid in the diagnosis, prognosis, and therapy of AAA progression.

Identification of novel biomarkers of abdominal aortic aneurysms by 2D-DIGE and MALDI-MS from AAA-thrombus-conditioned media.

In the search for novel biomarkers, noncandidate-based proteomic strategies open up new opportunities to gain a deeper insight into disease processes regarding their molecular mechanisms, the risk factors involved, and the monitoring of disease progression. To carry out these complex analyses, the combined use of gel electrophoresis with mass spectrometry (MS) represents a powerful choice. In addition, the introduction of protein dye labeling has notably improved the reliability of differential expression studies by increasing the statistical significance of the protein candidates.

Use of TOF-SIMS in vascular biology.

Secondary ion mass spectrometry is a technique used for surface analysis. The recent introduction of metal cluster ionization sources opened the possibility to probe biological tissues, due to its reduced in-source fragmentation. Despite its limitations in mass range of the molecules analyzed, a combination of minimal sample processing, sensibility, and unsurpassed lateral resolution makes TOF-SIMS a good tool for molecular imaging in pathology.

Gremlin is a downstream profibrotic mediator of transforming growth factor-beta in cultured renal cells.

Background/aims: Chronic kidney disease is characterized by accumulation of extracellular matrix in the tubulointerstitial area. Fibroblasts are the main matrix-producing cells. One source of activated fibroblasts is the epithelial mesenchymal transition (EMT).