Not too much, not too little-just the right amount: the story of YAP in the podocyte.

Chen et al. identify dysregulation of the transcriptional activator Yes-associated protein in the podocytes of diabetic mouse and human kidneys. Podocyte Yes-associated protein deficiency led to downregulation of the key transcription factor Wilms' tumor 1, and worsened podocyte injury in a mouse model of diabetic kidney injury.

Omicron variant neutralizing antibodies following BNT162b2 BA.4/5 versus mRNA-1273 BA.1 bivalent vaccination in patients with end-stage kidney disease.

Neutralization of Omicron subvariants by different bivalent vaccines has not been well evaluated. This study characterizes neutralization against Omicron subvariants in 98 individuals on dialysis or with a kidney transplant receiving the BNT162b2 (BA.4/BA.

Dual Role of Caspase 8 in Adipocyte Apoptosis and Metabolic Inflammation.

Unlabelled: Caspases are cysteine-aspartic proteases that were initially discovered to play a role in apoptosis. However, caspase 8, in particular, also has additional nonapoptotic roles, such as in inflammation. Adipocyte cell death and inflammation are hypothesized to be initiating pathogenic factors in type 2 diabetes.

Humoral Responses in the Omicron Era Following 3-Dose SARS-CoV-2 Vaccine Series in Kidney Transplant Recipients.

Unlabelled: Kidney transplant recipients (KTRs) have a diminished response to SARS-CoV-2 vaccination compared with immunocompetent individuals. Deeper understanding of antibody responses in KTRs following third-dose vaccination would enable identification of those who remain unprotected against Omicron.

Methods: We profiled antibody responses in KTRs pre- and at 1 and 3 mo post-third-dose SARS-CoV-2 mRNA-based vaccine.

Disruption of adipocyte YAP improves glucose homeostasis in mice and decreases adipose tissue fibrosis.

Objective: Adipose tissue is a very dynamic metabolic organ that plays an essential role in regulating whole-body glucose homeostasis. Dysfunctional adipose tissue hypertrophy with obesity is associated with fibrosis and type 2 diabetes. Yes-associated protein 1 (YAP) is a transcription cofactor important in the Hippo signaling pathway.

Magnetic Resonance Elastography-derived Stiffness Predicts Renal Function Loss and Is Associated With Microvascular Inflammation in Kidney Transplant Recipients.

Background: Organ stiffening can be caused by inflammation and fibrosis, processes that are common causes of transplant kidney dysfunction. Magnetic resonance elastography (MRE) is a contrast-free, noninvasive imaging modality that measures kidney stiffness. The objective of this study was to assess the ability of MRE to serve as a prognostic factor for renal outcomes.

NUAK1 promotes organ fibrosis via YAP and TGF-β/SMAD signaling.

Fibrosis is a central pathway that drives progression of multiple chronic diseases, yet few safe and effective clinical antifibrotic therapies exist. In most fibrotic disorders, transforming growth factor-β (TGF-β)-driven scarring is an important pathologic feature and a key contributor to disease progression. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are two closely related transcription cofactors that are important for coordinating fibrogenesis after organ injury, but how they are activated in response to tissue injury has, so far, remained unclear.

Myofibroblast YAP/TAZ activation is a key step in organ fibrogenesis.

Fibrotic diseases account for nearly half of all deaths in the developed world. Despite its importance, the pathogenesis of fibrosis remains poorly understood. Recently, the two mechanosensitive transcription cofactors YAP and TAZ have emerged as important profibrotic regulators in multiple murine tissues.

Inhibition of polar actin assembly by astral microtubules is required for cytokinesis.

During cytokinesis, the actin cytoskeleton is partitioned into two spatially distinct actin isoform specific networks: a β-actin network that generates the equatorial contractile ring, and a γ-actin network that localizes to the cell cortex. Here we demonstrate that the opposing regulation of the β- and γ-actin networks is required for successful cytokinesis. While activation of the formin DIAPH3 at the cytokinetic furrow underlies β-actin filament production, we show that the γ-actin network is specifically depleted at the cell poles through the localized deactivation of the formin DIAPH1.

Microfluidic Generation of Monodisperse Nanobubbles by Selective Gas Dissolution.

Nanotechnology currently enables the fabrication of uniform solid nanoparticles and liquid nano-emulsions, but not uniform gaseous nanobubbles (NBs). In this article, for the first time, a method based on microfluidics that directly produces monodisperse NBs is reported. Specifically, a two-component gas mixture of water-soluble nitrogen and water-insoluble octafluoropropane as the gas phase are used in a microfluidic bubble generator.

Imaging of renal fibrosis.

Purpose Of Review: Fibrosis is an important biomarker of chronic kidney injury, and a powerful predictor of renal outcome. Currently, the only method for measuring fibrotic burden is histologic analysis, which requires a kidney biopsy in humans, or kidney removal in animal models. These requirements have not only hindered our ability to manage patients effectively, but have also prevented a full understanding of renal fibrosis pathogenesis, and slowed the translation of new antifibrotic agents.

Overexpression of the Severe Acute Respiratory Syndrome Coronavirus-2 Receptor, Angiotensin-Converting Enzyme 2, in Diabetic Kidney Disease: Implications for Kidney Injury in Novel Coronavirus Disease 2019.

Objectives: Diabetes is associated with adverse outcomes, including death, after coronavirus disease 19 (COVID-19) infection. Beyond the lungs, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the etiologic agent of the COVID-19 pandemic, can infect a range of other tissues, including the kidney, potentially contributing to acute kidney injury in those with severe disease. We hypothesized that the renal abundance of angiotensin-converting enzyme (ACE) 2, the cell surface receptor for SARS-CoV-2, may be modulated by diabetes and agents that block the renin-angiotensin-aldosterone system (RAAS).

Renal histology in diabetic nephropathy predicts progression to end-stage kidney disease but not the rate of renal function decline.

Background: While histopathologic changes correlate with functional impairment in cross-sectional studies of diabetic nephropathy (DN), whether these findings predict future rate of kidney function loss remains uncertain. We thus sought to examine the relationship between kidney histopathology, incidence of end-stage kidney disease (ESKD), and rate of estimated glomerular filtration rate (eGFR) loss in DN.

Methods: In this longitudinal cohort study, we studied 50 adults diagnosed with biopsy-proven DN.

Reduced Flow in Delayed Graft Function as Assessed by IVIM Is Associated With Time to Recovery Following Kidney Transplantation.

Background: Delayed graft function (DGF), defined as the need for dialysis in the first week after kidney transplantation, frequently complicates posttransplantation care. The most common cause of DGF is ischemia-reperfusion injury (IRI). To date, no clinical tools can accurately estimate its severity, nor the time required for recovery of kidney function.

Validation of the Kidney Failure Risk Equation in Kidney Transplant Recipients.

Background: Predicting allograft failure in kidney transplant recipients can help plan renal replacement therapy and guide patient-provider communication. The kidney failure risk equation (KFRE) accurately predicts the need for dialysis in patients with chronic kidney disease (CKD), but has not been validated in kidney transplant recipients.

Objective: We sought to validate the 4-variable KFRE (age, sex, estimated glomerular filtration rate [eGFR], and urine albumin-to-creatinine ratio [ACR]) for prediction of 2- and 5-year death-censored allograft failure.

A common glomerular transcriptomic signature distinguishes diabetic kidney disease from other kidney diseases in humans and mice.

Background: Current uncertainties about the similarity between human diseases and their experimental models are hampering the development of new therapies. This is especially the case for diabetic kidney disease (DKD), the most common cause of end-stage kidney disease. To better understand the nature of the commonality between humans and their mouse models, we posed the question: in diabetic kidney disease are transcriptional profiles primarily disease-specific or species-specific?

Methods: We performed a meta-comparison of the glomerular transcriptomic characteristics of 133 human and 66 mouse samples including five human kidney diseases and five mouse models, validating expression patterns of a central node by immunohistochemistry.

Photoacoustic imaging of kidney fibrosis for assessing pretransplant organ quality.

Roughly 10% of the world's population has chronic kidney disease (CKD). In its advanced stages, CKD greatly increases the risk of hospitalization and death. Although kidney transplantation has revolutionized the care of advanced CKD, clinicians have limited ways of assessing donor kidney quality.

A new, easily generated mouse model of diabetic kidney fibrosis.

Our understanding of diabetic kidney disease pathogenesis has been hampered by the lack of easily generated pre-clinical animal models that faithfully recapitulate critical features of human disease. While most standard animal models develop manifestations of early stage diabetic injury such as hyperfiltration and mesangial matrix expansion, only a select few develop key late stage features such as interstitial fibrosis and reduced glomerular filtration rate. An underlying theme in these late stage disease models has been the addition of renin-angiotensin system hyperactivation, an important contributor to human disease pathogenesis.

Right ventricular fibrosis is associated with cardiac remodelling after pulmonary valve replacement.

Objective: The relationship between right ventricular (RV) fibrosis and right heart reverse remodelling following pulmonary valve replacement (PVR) has not been well studied in adults with repaired tetralogy of Fallot (rTOF). Our aims were to histologically quantify RV fibrosis and to explore the relationship between fibrosis severity and cardiac remodelling post-PVR.

Methods: Adults with rTOF and pre-PVR cardiovascular (CMR) imaging were consented to procurement of RV muscle during PVR.

Does Chronic Kidney Disease-Induced Cognitive Impairment Affect Driving Safety?

Purpose Of Review: One of the principal mechanisms by which illness can affect driving safety is by impairing cognition. Nevertheless, despite the substantial evidence demonstrating cognitive impairment in chronic kidney disease (CKD), little is known about the effects of CKD on driving safety.

Objective: Investigate the current national medical guidelines and research literature with respect to CKD and driving safety.

Magnetic Resonance Elastography to Assess Fibrosis in Kidney Allografts.

Background And Objectives: Fibrosis is a major cause of kidney allograft injury. Currently, the only means of assessing allograft fibrosis is by biopsy, an invasive procedure that samples <1% of the kidney. We examined whether magnetic resonance elastography, an imaging-based measure of organ stiffness, could noninvasively estimate allograft fibrosis and predict progression of allograft dysfunction.

The role of thrombectomy and diffusion-weighted imaging with MRI in post-transplant renal vein thrombosis: a case report.

Background: Surgical thrombectomy in the context of acute renal vein thrombosis (RVT) post-transplantation has had limited success, with considerable variation in the surgical techniques used. Unfortunately, it is usually followed by allograft nephrectomy within a few days if rapid allograft recovery does not ensue. We report a case of acute RVT in which nephrectomy was not performed despite a prolonged requirement for dialysis post-thrombectomy, but with recovery of renal function 2 weeks later.

Relationship between changes in blood pressure and left ventricular mass over 1 year in end-stage renal disease.

Objective: The optimal timing of blood pressure (BP) measurement is not firmly established for patients undergoing hemodialysis. We sought to assess which BP measurement change best correlates with changes in left ventricular mass index (LVMI) over 1 year in patients with end-stage renal disease.

Methods: Fifty-seven patients were included in a prospective cohort study comparing the cardiovascular impact of conversion to in-center nocturnal hemodialysis versus continuing conventional hemodialysis.