Endothelin blockade prevents the long-term cardiovascular and renal sequelae of acute kidney injury in mice.

Acute kidney injury (AKI) is common and associated with increased risks of cardiovascular and chronic kidney disease. Causative molecular/physiological pathways are poorly defined. There are no therapies to improve long-term outcomes.

Utility of interval kidney biopsy in ANCA-associated vasculitis.

Objectives: ANCA-associated vasculitis (AAV) is a rare autoimmune disorder that commonly involves the kidney. Early identification of kidney involvement, assessing treatment-response and predicting outcome are important clinical challenges. Here, we assessed the potential utility of interval kidney biopsy in AAV.

Deletion of the myeloid endothelin-B receptor confers long-term protection from angiotensin II-mediated kidney, eye and vessel injury.

The endothelin system may be an important player in hypertensive end-organ injury as endothelin-1 increases blood pressure and is pro-inflammatory. The immune system is emerging as an important regulator of blood pressure and we have shown that the early hypertensive response to angiotensin-II infusion was amplified in mice deficient of myeloid endothelin-B (ET) receptors (LysM-CreEdnrblox/lox). Hypothesizing that these mice would display enhanced organ injury, we gave angiotensin-II to LysM-CreEdnrblox/lox and littermate controls (Ednrblox/lox) for six weeks.

Long-term outcomes in elderly patients with ANCA-associated vasculitis.

Objective: ANCA-associated vasculitis (AAV) is a small vessel vasculitis that commonly presents in the elderly. However, there are few long-term outcome data for these patients. Here, we assessed long-term outcomes in a single-centre cohort of elderly patients with AAV.

Using prescribing very short answer questions to identify sources of medication errors: a prospective study in two UK medical schools.

Objective: To assess the utility and ability of the novel prescribing very short answer (VSA) question format to identify the sources of undergraduate prescribing errors when compared with the conventional single best answer (SBA) question format and assess the acceptability of machine marking prescribing VSAs.

Design: A prospective study involving analysis of data generated from a pilot two-part prescribing assessment.

Setting: Two UK medical schools.

A novel role for myeloid endothelin-B receptors in hypertension.

Aims: Hypertension is common. Recent data suggest that macrophages (Mφ) contribute to, and protect from, hypertension. Endothelin-1 (ET-1) is the most potent endogenous vasoconstrictor with additional pro-inflammatory properties.

Granulocyte macrophage-colony stimulating factor: A key modulator of renal mononuclear phagocyte plasticity.

Macrophage-colony stimulating factor (M-CSF) and granulocyte macrophage-colony stimulating factor (GM-CSF) play key roles in the differentiation of macrophages and dendritic cells (DCs). We examined the effect of treatment with M-CSF-containing macrophage medium or GM-CSF-containing DC medium upon the phenotype of murine bone marrow-derived macrophages and DCs. Culture of macrophages for 5 days in DC medium reduced F4/80 expression and increased CD11c expression with cells effectively stimulating T cell proliferation in a mixed lymphocyte reaction.

Variation in passing standards for graduation-level knowledge items at UK medical schools.

Objectives: Given the absence of a common passing standard for students at UK medical schools, this paper compares independently set standards for common 'one from five' single-best-answer (multiple-choice) items used in graduation-level applied knowledge examinations and explores potential reasons for any differences.

Methods: A repeated cross-sectional study was conducted. Participating schools were sent a common set of graduation-level items (55 in 2013-2014; 60 in 2014-2015).

Working with Commercially Available Quantum Dots for Immunofluorescence on Tissue Sections.

Quantum dots are semiconductor fluorescent nanocrystals that exhibit excellent characteristics compared with more commonly used organic fluorescent dyes. For many years quantum dot conjugated products have been available in multiple forms for fluorescence imaging of tissue sections under the trademark name Qdot®. They have much increased brightness, narrow emission spectrum, large Stokes shift and photostability compared with conventional organic fluorescent dyes, which together make them the fluorophores of choice for demanding requirements.

Choice of Illumination System & Fluorophore for Multiplex Immunofluorescence on FFPE Tissue Sections.

The recent availability of novel dyes and alternative light sources to facilitate complex tissue immunofluorescence studies such as multiplex labelling has not been matched by reports critically evaluating the considerations and relative benefits of these new tools, particularly in combination. Product information is often limited to wavelengths used for older fluorophores (FITC, TRITC & corresponding Alexa dyes family). Consequently, novel agents such as Quantum dots are not widely appreciated or used, despite highly favourable properties including extremely bright emission, stability and potentially reduced tissue autofluorescence at the excitation wavelength.

Hemin Preconditioning Upregulates Heme Oxygenase-1 in Deceased Donor Renal Transplant Recipients: A Randomized, Controlled, Phase IIB Trial.

Background: The enzyme heme oxygenase-1 (HO-1) degrades heme and protects against ischemia-reperfusion injury. Monocytes/macrophages are the major source of HO-1 and higher levels improve renal transplant outcomes. Heme arginate (HA) safely induces HO-1 in humans.

Benefits of an expanded use of plasma exchange for anti-neutrophil cytoplasmic antibody-associated vasculitis within a dedicated clinical service.

Background: Current recommendations for ANCA-associated vasculitis (AAV) support its management within a dedicated clinical service. Therapies for AAV are imperfect with many patients failing to achieve disease control and others experiencing disease relapse. Plasma exchange (PEX) may be beneficial especially when the kidney is involved.

Circulating IgM Requires Plasma Membrane Disruption to Bind Apoptotic and Non-Apoptotic Nucleated Cells and Erythrocytes.

Autoimmunity is associated with defective phagocytic clearance of apoptotic cells. IgM deficient mice exhibit an autoimmune phenotype consistent with a role for circulating IgM antibodies in apoptotic cell clearance. We have extensively characterised IgM binding to non-apoptotic and apoptotic mouse thymocytes and human Jurkat cells using flow cytometry, confocal imaging and electron microscopy.

The utility of the additive EuroSCORE, RIFLE and AKIN staging scores in the prediction and diagnosis of acute kidney injury after cardiac surgery.

Background/aims: Acute kidney injury (AKI) following cardiac surgery is a complication associated with high rates of morbidity and mortality. We compared staging systems for the diagnosis of AKI after cardiac surgery, and assessed pre-operative factors predictive of post-operative AKI.

Methods: Clinical data, surgical risk scores, procedure and clinical outcome were obtained on all 4,651 patients undergoing cardiac surgery to the Royal Infirmary of Edinburgh between April 2006 and March 2011, of whom 4,572 had sufficient measurements of creatinine before and after surgery to permit inclusion and analysis.

Apoptotic cell administration is detrimental in murine renal ischaemia reperfusion injury.

Background: Acute kidney injury induced by renal ischaemia reperfusion injury (IRI) is characterised by renal failure, acute tubular necrosis (ATN), inflammation and microvascular congestion. The administration of apoptotic cells (ACs) has been shown to reduce inflammation in various organs including the liver and kidney. This study explored whether AC administration prior to the induction of renal IRI was protective.

Utility of renal biopsy in the clinical management of renal disease.

Characterizing chronic kidney disease (CKD) at all stages is an essential part of rational management and the renal biopsy plays a key role in defining the processes involved. There remain no global guidelines available to the renal community on indications for this important diagnostic, prognostic, and relatively safe test. Although most nephrologists recognize several clear indications for a renal biopsy, it is still underutilized.

Paradoxical effects of heme arginate on survival of myocutaneous flaps.

Ischemia reperfusion injury (IRI) contributes to partial flap and solid organ transplant failure. Heme-oxygenase 1 (HO-1) is an inducible, cytoprotective enzyme which protects against IRI in solid organ transplant models. Heme arginate (HA), a HO-1 inducer, is a promising, translatable, preconditioning agent.

Endothelin antagonism and its role in the treatment of hypertension.

Hypertension contributes greatly to global disease burden and in many patients current treatments do not adequately control blood pressure (BP). Endothelin-1 (ET-1) is a potent vasoconstrictor that is implicated in the pathogenesis of hypertension, including the hypertension that is often associated with chronic kidney disease (CKD) and the metabolic syndrome. ET receptor antagonists, currently licensed for the treatment of pulmonary arterial hypertension and scleroderma-related digital ulcers, are being investigated for the treatment of hypertension.

Computed tomography angiography in the diagnosis of ANCA-associated small- and medium-vessel vasculitis.

Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis that typically occurs without detectable antineutrophil cytoplasmic antibody. It leads to aneurysm formation by affecting muscular arteries, usually those of medium size but also occasionally those of small size. Kidney involvement is common, leading to reduced glomerular filtration rate, hypertension, rupture of renal arterial aneurysms causing perinephric hematomas, and renal infarctions in those with severe vasculitis.