Atypical Polycystic Kidney Disease as defined by Imaging.

Using age- and height-adjusted total kidney volume, the Mayo Clinic Imaging Classification provides a validated approach to assess the risk of chronic kidney disease (CKD) progression in autosomal dominant polycystic kidney disease (ADPKD), but requires excluding patients with atypical imaging patterns, whose clinical characteristics have been poorly defined. We report an analysis of the prevalence, clinical and genetic characteristics of patients with atypical polycystic kidney disease by imaging. Patients from the extended Toronto Genetic Epidemiology Study of Polycystic Kidney Disease recruited between 2016 and 2018 completed a standardized clinical questionnaire, kidney function assessment, genetic testing, and kidney imaging by magnetic resonance or computed tomography.

Minimal Change Disease After First Dose of Pfizer-BioNTech COVID-19 Vaccine: A Case Report and Review of Minimal Change Disease Related to COVID-19 Vaccine.

Rationale: While severe complications are generally uncommon with novel coronavirus disease 2019 (COVID-19) vaccine, there has been a steady increase in the number of patients presenting with nephrotic syndrome and acute kidney injury after the administration of COVID-19 vaccine. Physicians should be made aware of minimal change disease as a potential complication associated with COVID-19 vaccine.

Presenting Concerns: A 60-year-old male without significant past medical history presented with new onset of nephrotic syndrome approximately 10 days after his first dose of Pfizer-BioNTech COVID-19 vaccine.

TDAG51 (T-Cell Death-Associated Gene 51) Is a Key Modulator of Vascular Calcification and Osteogenic Transdifferentiation of Arterial Smooth Muscle Cells.

Objective: Cardiovascular disease is the primary cause of mortality in patients with chronic kidney disease. Vascular calcification (VC) in the medial layer of the vessel wall is a unique and prominent feature in patients with advanced chronic kidney disease and is now recognized as an important predictor and independent risk factor for cardiovascular and all-cause mortality in these patients. VC in chronic kidney disease is triggered by the transformation of vascular smooth muscle cells (VSMCs) into osteoblasts as a consequence of elevated circulating inorganic phosphate (P) levels, due to poor kidney function.

Intrafamilial Variability of ADPKD.

Introduction: Discordance in kidney disease severity between affected relatives is a recognized feature of autosomal dominant polycystic kidney disease (ADPKD). Here, we report a systematic study of a large cohort of families to define the prevalence and clinical features of intrafamilial discordance in ADPKD.

Methods: The extended Toronto Genetic Epidemiology Study of Polycystic Kidney Disease (eTGESP) cohort includes 1390 patients from 612 unrelated families with ADPKD ascertained in a regional polycystic kidney disease center.

Nuclear transportation of exogenous epidermal growth factor receptor and androgen receptor via extracellular vesicles.

Epidermal growth factor receptor (EGFR) plays a central role in the progression of several human malignancies. Although EGFR is a membrane receptor, it undergoes nuclear translocation, where it has a distinct signalling pathway. Herein, we report a novel mechanism by which cancer cells can directly transport EGFR to the nucleus of other cells via extracellular vesicles (EVs).

Coronary artery calcification, cardiovascular events, and death: a prospective cohort study of incident patients on hemodialysis.

Background: Coronary calcification in patients with end-stage renal disease (ESRD) is associated with an increased risk of cardiovascular outcomes and death from all causes. Previous evidence has been limited by short follow-up periods and inclusion of a heterogeneous cluster of events in the primary analyses.

Objective: To describe coronary calcification in patients incident to ESRD, and to identify whether calcification predicts vascular events or death.

4-Phenylbutyrate inhibits tunicamycin-induced acute kidney injury via CHOP/GADD153 repression.

Different forms of acute kidney injury (AKI) have been associated with endoplasmic reticulum (ER) stress; these include AKI caused by acetaminophen, antibiotics, cisplatin, and radiocontrast. Tunicamycin (TM) is a nucleoside antibiotic known to induce ER stress and is a commonly used inducer of AKI. 4-phenylbutyrate (4-PBA) is an FDA approved substance used in children who suffer from urea cycle disorders.

Colchicine attenuates renal injury in a model of hypertensive chronic kidney disease.

Hypertension is a risk factor for chronic kidney disease, particularly when associated with impaired renal autoregulation and thereby increased intraglomerular pressure (Pgc). Elevated Pgc can be modeled in vitro by exposing glomerular mesangial cells to mechanical strain. We previously showed that RhoA mediates strain-induced matrix production.

Regulation of the tumor suppressor PTEN through exosomes: a diagnostic potential for prostate cancer.

PTEN is a potent tumor-suppressor protein. Aggressive and metastatic prostate cancer (PC) is associated with a reduction or loss of PTEN expression. PTEN reduction often occurs without gene mutations, and its downregulation is not fully understood.

Stroke prevention in atrial fibrillation patients with chronic kidney disease.

Chronic kidney disease (CKD) is prevalent in elderly patients with atrial fibrillation and is an independent risk factor for stroke. Warfarin anticoagulation is efficacious for stroke prevention in atrial fibrillation patients with moderate CKD (stage III, estimated glomerular filtration rate 30-59 mL/min), but recent observational studies have challenged its value for patients with end-stage renal disease requiring dialysis. The novel oral anticoagulants (i.

TGFβ receptor I transactivation mediates stretch-induced Pak1 activation and CTGF upregulation in mesangial cells.

Increased intraglomerular pressure is an important pathogenic determinant of kidney fibrosis in the progression of chronic kidney disease, and can be modeled by exposing glomerular mesangial cells (MC) to mechanical stretch. MC produce extracellular matrix and profibrotic cytokines, including connective tissue growth factor (CTGF) when stretched. We show that p21-activated kinase 1 (Pak1) is activated by stretch in MC in culture and in vivo in a process marked by elevated intraglomerular pressures.

Propagation of human prostate cancer stem-like cells occurs through EGFR-mediated ERK activation.

Prostate cancer stem-like cells (PCSCs) are being intensely investigated largely owing to their contributions towards prostate tumorigenesis, however, our understanding of PCSC biology, including their critical pathways, remains incompletely understood. While epidermal growth factor (EGF) is widely used in maintaining PCSC cells in vitro, the importance of EGF-dependent signaling and its downstream pathways in PCSC self-renewal are not well characterized. By investigating DU145 sphere cells, a population of prostate cancer cells with stem-like properties, we report here that epidermal growth factor receptor (EGFR) signaling plays a critical role in the propagation of DU145 PCSCs.

BRCA1 is a novel target to improve endothelial dysfunction and retard atherosclerosis.

Objective: BRCA1, a tumor suppressor gene implicated in breast and ovarian cancers, exerts multiple effects on DNA repair and affords resistance against cellular stress responses. We hypothesized that BRCA1 limits endothelial cell apoptosis and dysfunction, and via this mechanism attenuates atherosclerosis.

Methods: Loss and gain of function were achieved in cultured endothelial cells by silencing and overexpressing BRCA1, respectively.

Anticoagulants in patients with atrial fibrillation and end-stage renal disease.

Atrial fibrillation (AF) is a common cardiac arrhythmia and is associated with an increased risk for thromboembolic stroke. Anticoagulant therapy has been shown to reduce the risk for ischemic stroke in patients with AF; however, these studies have excluded patients with end-stage renal disease (ESRD). This review examines the relationships between ESRD, AF, and the use of anticoagulants to prevent ischemic stroke.

MicroRNA-145 targeted therapy reduces atherosclerosis.

Background: MicroRNA are essential posttranscriptional modulators of gene expression implicated in various chronic diseases. Because microRNA-145 is highly expressed in vascular smooth muscle cells (VSMC) and regulates VSMC fate and plasticity, we hypothesized that it may be a novel regulator of atherosclerosis and plaque stability.

Methods And Results: Apolipoprotein E knockout mice (ApoE(-/-)) mice were treated with either a microRNA-145 lentivirus under the control of the smooth muscle cell (SMC)-specific promoter SM22α or a SM22α control lentivirus before commencing the Western diet for 12 weeks.

Anticoagulants in atrial fibrillation patients with chronic kidney disease.

Atrial fibrillation is an important cause of preventable, disabling stroke and is particularly frequent in patients with chronic kidney disease (CKD). Stage 3 CKD is an independent risk factor for stroke in patients with atrial fibrillation. Warfarin anticoagulation is efficacious for stroke prevention in atrial fibrillation patients with stage 3 CKD, but recent observational studies have challenged its value for patients with end-stage renal disease and atrial fibrillation.

ER stress contributes to renal proximal tubule injury by increasing SREBP-2-mediated lipid accumulation and apoptotic cell death.

Renal proximal tubule injury is induced by agents/conditions known to cause endoplasmic reticulum (ER) stress, including cyclosporine A (CsA), an immunosuppressant drug with nephrotoxic effects. However, the underlying mechanism by which ER stress contributes to proximal tubule cell injury is not well understood. In this study, we report lipid accumulation, sterol regulatory element-binding protein-2 (SREBP-2) expression, and ER stress in proximal tubules of kidneys from mice treated with the classic ER stressor tunicamycin (Tm) or in human renal biopsy specimens showing CsA-induced nephrotoxicity.

SREBP-1 activation by glucose mediates TGF-β upregulation in mesangial cells.

Glomerular matrix accumulation is a hallmark of diabetic nephropathy. Recent studies showed that overexpression of the transcription factor sterol-responsive element-binding protein (SREBP)-1 induces pathology reminiscent of diabetic nephropathy, and SREBP-1 upregulation was observed in diabetic kidneys. We thus studied whether SREBP-1 is activated by high glucose (HG) and mediates its profibrogenic responses.

α-Mannosidase 2C1 attenuates PTEN function in prostate cancer cells.

PTEN dephosphorylates the 3-position phosphate of phosphatidylinositol 3,4,5 triphosphate (PIP(3)), thereby inhibiting AKT activation. Although attenuation of PTEN function has a major role in tumourigenesis, the underlying mechanisms remain unclear. Here we show that α-mannosidase 2C1 (MAN2C1) inhibits PTEN function in prostate cancer (PC) cells and is associated with a reduction in PTEN function in primary PC.

Low-intensity adjusted-dose warfarin for the prevention of hemodialysis catheter failure: a randomized, controlled trial.

Background And Objectives: To determine whether warfarin prolongs the time to first mechanical-catheter failure.

Design, Setting, Participants, & Measurements: This was a multicenter parallel-group randomized controlled trial with blinding of participants, trial staff, clinical staff, outcome assessors, and data analysts. Randomization was in a 1:1 ratio in blocks of four and was concealed by use of fax to a central pharmacy.

Induction of the unfolded protein response after monocyte to macrophage differentiation augments cell survival in early atherosclerotic lesions.

Endoplasmic reticulum (ER) stress causes macrophage cell death within advanced atherosclerotic lesions, thereby contributing to necrotic core formation and increasing the risk of atherothrombotic disease. However, unlike in advanced lesions, the appearance of dead/apoptotic macrophages in early lesions is less prominent. Given that activation of the unfolded protein response (UPR) is detected in early lesion-resident macrophages and can enhance cell survival against ER stress, we investigated whether UPR activation occurs after monocyte to macrophage differentiation and confers a cytoprotective advantage to the macrophage.

Shank-interacting protein-like 1 promotes tumorigenesis via PTEN inhibition in human tumor cells.

Inactivation of phosphatase and tensin homolog (PTEN) is a critical step during tumorigenesis, and PTEN inactivation by genetic and epigenetic means has been well studied. There is also evidence suggesting that PTEN negative regulators (PTEN-NRs) have a role in PTEN inactivation during tumorigenesis, but their identity has remained elusive. Here we have identified shank-interacting protein-like 1 (SIPL1) as a PTEN-NR in human tumor cell lines and human primary cervical cancer cells.

Mechanical strain-induced RhoA activation requires NADPH oxidase-mediated ROS generation in caveolae.

Increased intraglomerular pressure leads to kidney fibrosis, and can be modeled by exposing glomerular mesangial cells (MC) to mechanical strain. We previously showed that RhoA mediates strain-induced matrix production. Here we investigate whether reactive oxygen species (ROS) are required for RhoA activation.