Author Correction: Glomerulocapillary miRNA response to HLA-class I antibody in vitro and in vivo.

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Recommendations for mRNA analysis of micro-dissected glomerular tufts from paraffin-embedded human kidney biopsy samples.

Background: Glomeruli are excellent pre-determined natural structures for laser micro-dissection. Compartment-specific glomerular gene expression analysis of formalin-fixed paraffin-embedded renal biopsies could improve research applications. The major challenge for such studies is to obtain good-quality RNA from small amounts of starting material, as applicable for the analysis of glomerular compartments.

Glomerulocapillary miRNA response to HLA-class I antibody in vitro and in vivo.

Unlabelled: Changes in miRNA expression glomerular of capillaries during antibody-mediated rejection (ABMR) are poorly understood and could contribute to the deleterious inflammation and fibrosis of ABMR via suppression of target genes. A better understanding could lead to novel diagnostic tools and reveal novel therapeutic targets. We explored deregulated miRNAs in an glomeruloendothelial in vitro model of ABMR due to class I human leukocyte antigen (HLA) with and without complement activation.

The Phenotypic Spectrum of Nephropathies Associated with Mutations in Diacylglycerol Kinase .

The recent discovery of mutations in the gene encoding diacylglycerol kinase (DGKE) identified a novel pathophysiologic mechanism leading to HUS and/or MPGN. We report ten new patients from eight unrelated kindreds with DGKE nephropathy. We combined these cases with all previously published cases to characterize the phenotypic spectrum and outcomes of this new disease entity.

Autophagy in kidney transplants of sirolimus treated recipients.

Background: Mammalian target of rapamycin (mTOR) inhibitors are increasingly used as immunosuppressive agents in kidney transplantation. In the experimental setting it has been shown that mTOR inhibitors promote autophagy, but the concept that this might also occur in transplant patients has not been addressed.

Objectives: This study was designed to investigate the association between mTOR inhibition and autophagy in renal transplants under routine clinical conditions.

Comparison of different normalization strategies for the analysis of glomerular microRNAs in IgA nephropathy.

Small nucleolar RNAs (snoRNAs) have been used for normalization in glomerular microRNA (miRNA) quantification without confirmation of validity. Our aim was to identify glomerular reference miRNAs in IgA nephropathy. We compared miRNAs in human paraffin-embedded renal biopsies from patients with cellular-crescentic IgA-GN (n = 5; crescentic IgA-GN) and non-crescentic IgA-GN (n = 5; IgA-GN) to mild interstitial nephritis without glomerular abnormalities (controls, n = 5).

Acid Sphingomyelinase Promotes Endothelial Stress Response in Systemic Inflammation and Sepsis.

The pathophysiology of sepsis involves activation of acid sphingomyelinase (SMPD1) with subsequent generation of the bioactive mediator ceramide. We herein evaluated the hypothesis that the enzyme exerts biological effects in endothelial stress response. Plasma-secreted sphingomyelinase activity, ceramide generation and lipid raft formation were measured in human microcirculatory endothelial cells (HMEC-1) stimulated with serum obtained from sepsis patients.

Immune Complex-Type Deposits in the Fischer-344 to Lewis Rat Model of Renal Transplantation and a Subset of Human Transplant Glomerulopathy.

Background: Antibody-mediated rejection is a leading cause for renal transplant loss. Rodent models are useful to dissect pathomechanisms and to develop treatment strategies. Although used for decades as a model, glomerular histopathological findings of Fischer-344 kidneys transplanted into Lewis rats have never been comprehensively described.

Effect of TNF-alpha blockade on coagulopathy and endothelial cell activation in xenoperfused porcine kidneys.

Background: Following pig-to-primate kidney transplantation, endothelial cell activation and xenogenic activation of the recipient's coagulation eventually leading to organ dysfunction and microthrombosis can be observed. In this study, we examined the effect of a TNF-receptor fusion protein (TNF-RFP) on endothelial cell activation and coagulopathy utilizing an appropriate ex vivo perfusion system.

Methods: Using an ex vivo perfusion circuit based on C1-Inhibitor (C1-Inh) and low-dose heparin administration, we have analyzed consumptive coagulopathy following contact of human blood with porcine endothelium.

Nephrotic syndrome and thrombotic microangiopathy caused by cobalamin C deficiency.

Background: Cobalamin C (CblC) defects are inherited autosomal recessive disorders of vitamin B12 metabolism due to mutations in the MMACHC gene. Renal manifestations include thrombotic microangiopathy (TMA), acute or chronic renal failure, tubulointerstitial nephritis, and proximal renal tubular acidosis. However, reports about glomerular pathologies are scarce.

Preserved Expression of mRNA Coding von Willebrand Factor-Cleaving Protease ADAMTS13 by Selenite and Activated Protein C.

In sepsis, the severity-dependent decrease of von Willebrand factor (VWF)-inactivating protease, a disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13), results in platelet aggregation and consumption, leading to sepsis-associated thrombotic microangiopathy (TMA) and organ failure. Previous reports assessing its functional deficiency have pinpointed involvement of autoantibodies or mutations to propagate thrombotic thrombocytopenic purpura (TTP). However, mechanisms of acquired ADAMTS13 deficiency during host response remain unclear.

Impact of antibiotic treatment intensity on long-term sepsis-associated kidney injury in a polymicrobial peritoneal contamination and infection model.

Background/aims: Long-term kidney affections after sepsis are poorly understood. Animal models for investigating kidney damage in the late phase of disease progression are limited. The aim of this study was to investigate the impact of two antibiotic regimes on persistence of kidney injury after peritonitis.

Progressive multifocal cerebral infarction in a young kidney transplant recipient due to thrombotic microangiopathy.

Background: Renal transplant recipients frequently experience neurological complications. Whereas ischemic stroke, cerebral haemorrhage or hypertensive encephalopathy often result from vascular alterations prior to transplantation, other cerebral diseases like CNS infections, primary brain tumors and drug induced neurotoxicity may develop as consequences of the required post-transplant immunosuppressive treatment.

Case Presentation: Here we report on an unusual clinical course of a young kidney transplant recipient with a cluster of fulminant necrotic brain lesions within a period of two months due to thrombotic microangiopathy.

Cardiac metastasis from a urothelial cell carcinoma: a commented case report.

We present a case of a middle-aged male patient who was admitted to our institution because of the supposed diagnosis of endocarditis/myocarditis. Echocardiographic findings revealed cystic mass in the left myocardial wall as well as floating structures at the lateral papillary muscle, mimicking endocarditis/myocarditis. Due to progressive urinary retention and clinical signs of a beginning ileus, an abdominal and thoracic computed tomographic scan was performed, which demonstrated a large diverticle of the urinary bladder with expansive tumorous wall mass.

Histopathological and clinical findings in renal transplants with Banff type II and III acute cellular rejection without tubulointerstitial infiltrates.

According to the Banff guidelines for renal transplants, pure endothelialitis without any tubulointerstitial infiltrates (with the Banff components v ≥ 1, i0, t0) has to be called acute cellular rejection (ACR). The pathophysiology of this rare lesion abbreviated as v_only is currently unclear, as well as its clinical, serological, and prognostic implications. Therefore, we conducted this retrospective comparative study.

Physical exercise induces specific adaptations resulting in reduced organ injury and mortality during severe polymicrobial sepsis.

Objectives: High physical activity levels are associated with wide-ranging health benefits, disease prevention, and longevity. In the present study, we examined the impact of regular physical exercise on the severity of organ injury and survival probability, as well as characteristics of the systemic immune and metabolic response during severe polymicrobial sepsis.

Design: Animal study.

Glomerular mRNA expression of prothrombotic and antithrombotic factors in renal transplants with thrombotic microangiopathy.

Background: Thrombotic microangiopathy (TMA) in renal transplants (rTx-TMA) is a serious complication and is usually either recurrent TMA (RecTMA) due to humoral rejection (HR-TMA) or due to calcineurin inhibitor toxicity (CNI-TMA). Although the triggers are known, our knowledge about the thrombogenic transcriptome changes in the microvessels is rudimentary.

Methods: We examined the expression of several prothrombotic and antithrombotic genes in 25 biopsies with rTx-TMA (6 RecTMA, 9 HR-TMA, and 10 CNI-TMA) and 8 controls.

The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network.

Background: Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking antibody, has been approved for the treatment of metastatic melanoma and induces adverse events (AE) in up to 64% of patients. Treatment algorithms for the management of common ipilimumab-induced AEs have lead to a reduction of morbidity, e.g.

Hyperresponsiveness of mice deficient in plasma-secreted sphingomyelinase reveals its pivotal role in early phase of host response.

Plasma secretion of acid sphingomyelinase is a hallmark of cellular stress response resulting in the formation of membrane embedded ceramide-enriched lipid rafts and the reorganization of receptor complexes. Consistently, decompartmentalization of ceramide formation from inert sphingomyelin has been associated with signaling events and regulation of the cellular phenotype. Herein, we addressed the question of whether the secretion of acid sphingomyelinase is involved in host response during sepsis.

Plexiform vasculopathy of severe pulmonary arterial hypertension and microRNA expression.

Background: Recent studies have revealed that microRNAs (miRNAs) play a key role in the control of angiogenesis and vascular remodeling. Specific miRNAs in plexiform vasculopathy of severe pulmonary arterial hypertension (PAH) in humans have not yet been investigated.

Methods: We analyzed expression of miR-143/145 (vascular smooth muscle-specific), miR-126 (endothelial-specific) and related mRNAs in plexiform (PLs) and concentric lesions (CLs), which had been laser-microdissected from specimens of formalin-fixed, paraffin-embedded, explanted lungs of PAH patients (n = 12) and unaffected controls (n = 8).

Angiopoietin-2 in acute liver failure.

Objective: Angiopoietin-2, an antagonistic ligand of the endothelial Tie2 receptor, has been identified as a gatekeeper of endothelial activation. We examined whether the release of Angiopoietin-2 correlates with surrogates of organ dysfunction and outcome in patients with acute liver failure.

Design: Retrospective clinical and immunohistological study.

Arteriolar vascular smooth muscle cell differentiation in benign nephrosclerosis.

Background: Benign nephrosclerosis (bN) is the most prevalent form of hypertensive damage in kidney biopsies. It is defined by early hyalinosis and later fibrosis of renal arterioles. Despite its high prevalence, very little is known about the contribution of arteriolar vascular smooth muscle cells (VSMCs) to bN.

The synthetic tie2 agonist peptide vasculotide protects against vascular leakage and reduces mortality in murine abdominal sepsis.

Introduction: Angiopoietin-1 (Angpt1), the natural agonist ligand for the endothelial Tie2 receptor, is a non-redundant endothelial survival and vascular stabilization factor that reduces endothelial permeability and inhibits leukocyte-endothelium interactions. Here we evaluate the efficacy of a novel polyethylene glycol (PEG)-clustered Tie2 agonist peptide, Vasculotide (VT), to protect against vascular leakage and mortality in a murine model of polymicrobial abdominal sepsis.

Methods: Polymicrobial abdominal sepsis in C57BL6 mice was induced by cecal-ligation-and-puncture (CLP).