Plasma proteomics of acute tubular injury.

The kidney tubules constitute two-thirds of the cells of the kidney and account for the majority of the organ's metabolic energy expenditure. Acute tubular injury (ATI) is observed across various types of kidney diseases and may significantly contribute to progression to kidney failure. Non-invasive biomarkers of ATI may allow for early detection and drug development.

Glomerular Elasticity and Gene Expression Patterns Define Two Phases of Alport Nephropathy.

Objectives: To understand the early stages if Alport nephropathy, we characterize the structural, functional, and biophysical properties of glomerular capillaries and podocytes in mice, analyze kidney cortex transcriptional profiles at three time points, and investigate the effects of the ER stress mitigation by TUDCA on these parameters. We use human FSGS associated genes to identify molecular pathways rescued by TUDCA.

Findings: We define a disease progression timeline in mice.

Demographic and Clinical Factors Associated With SARS-CoV-2 Spike 1 Antibody Response Among Vaccinated US Adults: the C4R Study.

This study investigates correlates of anti-S1 antibody response following COVID-19 vaccination in a U.S. population-based meta-cohort of adults participating in longstanding NIH-funded cohort studies.

Eculizumab Use in Scleroderma Renal Crisis With Thrombotic Microangiopathy: A Case Report.

A Black woman in her 40s with past medical history significant for obesity treated with Roux-en-Y bypass surgery and a history of Raynaud's phenomenon, presented with acute pulmonary edema secondary to severe malignant hypertension and critically accelerated acute kidney injury, with evidence of systemic microangiopathic hemolytic anemia in the setting of clinical suspicion of systemic sclerosis sine scleroderma. Renin-angiotensin system blockade (angiotensin-converting enzyme inhibitor) was immediately started at the maximum possible dose in the setting of scleroderma renal crisis. Despite better control of blood pressure and volume status, kidney function continued to rapidly decline, thus a decision was made to go ahead with a kidney biopsy on day 3 of admission, which revealed severe features of scleroderma renal crisis with active thrombotic microangiopathy.

Kidney Biopsy Utility: Patient and Clinician Perspectives from the Kidney Precision Medicine Project.

Rationale & Objective: Limited data exist on patient perspectives of the implications of kidney biopsies. We explored patients' perspectives alongside those of clinicians to better understand how kidney biopsies affect patients' viewpoints and the clinical utility of biopsies.

Study Design: Prospective Cohort Study.

Molecular Signatures of Glomerular Neovascularization in a Patient with Diabetic Kidney Disease.

The Kidney Precision Medicine Project (KPMP) aims to create a kidney tissue atlas, define disease subgroups, and identify critical cells, pathways, and targets for novel therapies through molecular investigation of human kidney biopsies obtained from participants with AKI or CKD. We present the case of a 66-year-old woman with diabetic kidney disease who underwent a protocol KPMP kidney biopsy. Her clinical history included diabetes mellitus complicated by neuropathy and eye disease, increased insulin resistance, hypertension, albuminuria, and relatively preserved glomerular filtration rate (early CKD stage 3a).

Defining the molecular correlate of arteriolar hyalinosis in kidney disease progression by integration of single cell transcriptomic analysis and pathology scoring.

Arteriolar hyalinosis in kidneys is an independent predictor of cardiovascular disease, the main cause of mortality in chronic kidney disease (CKD). The underlying molecular mechanisms of protein accumulation in the subendothelial space are not well understood. Using single cell transcriptomic data and whole slide images from kidney biopsies of patients with CKD and acute kidney injury in the Kidney Precision Medicine Project, the molecular signals associated with arteriolar hyalinosis were evaluated.

Clonal dynamics of alloreactive T cells in kidney allograft rejection after anti-PD-1 therapy.

Kidney transplant recipients are at particular risk for developing tumors, many of which are now routinely treated with immune checkpoint inhibitors (ICIs); however, ICI therapy can precipitate transplant rejection. Here, we use TCR sequencing to identify and track alloreactive T cells in a patient with melanoma who experienced kidney transplant rejection following PD-1 inhibition. The treatment was associated with a sharp increase in circulating alloreactive CD8 T cell clones, which display a unique transcriptomic signature and were also detected in the rejected kidney but not at tumor sites.

Collaborative Cohort of Cohorts for COVID-19 Research (C4R) Study: Study Design.

The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults comprising 14 established US prospective cohort studies. Starting as early as 1971, investigators in the C4R cohort studies have collected data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R links this pre-coronavirus disease 2019 (COVID-19) phenotyping to information on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and acute and postacute COVID-related illness.

On-Site, On-Demand 3D-Printed Nasopharyngeal Swabs to Improve the Access of Coronavirus Disease-19 Testing.

Diagnostic testing that facilitates containment, surveillance, and treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or future respiratory viruses, depends on a sample collection device that efficiently collects nasopharyngeal tissue and that can be manufactured on site when an outbreak or public health emergency is declared by a government. Here two novel stereolithography-based three-dimensional (3D)-printed nasopharyngeal swabs are reported which are made using a biocompatible and sterilizable photoresist. Such swabs are readily manufactured on-site and on-demand to ensure availability, if supply chain shortages emerge.

Discovery of Autoantibodies Targeting Nephrin in Minimal Change Disease Supports a Novel Autoimmune Etiology.

Background: Failure of the glomerular filtration barrier, primarily by loss of slit diaphragm architecture, underlies nephrotic syndrome in minimal change disease. The etiology remains unknown. The efficacy of B cell-targeted therapies in some patients, together with the known proteinuric effect of anti-nephrin antibodies in rodent models, prompted us to hypothesize that nephrin autoantibodies may be present in patients with minimal change disease.

PODO: Trial Design: Phase 2 Study of PF-06730512 in Focal Segmental Glomerulosclerosis.

Introduction: Focal segmental glomerulosclerosis (FSGS) is characterized by proteinuria and a histologic pattern of glomerular lesions of diverse etiology that share features including glomerular scarring and podocyte foot process effacement. Roundabout guidance receptor 2 (ROBO2)/slit guidance ligand 2 (SLIT2) signaling destabilizes the slit diaphragm and reduces podocyte adhesion to the glomerular basement membrane (GBM). Preclinical studies suggest that inhibition of glomerular ROBO2/SLIT2 signaling can stabilize podocyte adhesion and reduce proteinuria.

KIM-1 mediates fatty acid uptake by renal tubular cells to promote progressive diabetic kidney disease.

Tubulointerstitial abnormalities are predictive of the progression of diabetic kidney disease (DKD), and their targeting may be an effective means for prevention. Proximal tubular (PT) expression of kidney injury molecule (KIM)-1, as well as blood and urinary levels, are increased early in human diabetes and can predict the rate of disease progression. Here, we report that KIM-1 mediates PT uptake of palmitic acid (PA)-bound albumin, leading to enhanced tubule injury with DNA damage, PT cell-cycle arrest, interstitial inflammation and fibrosis, and secondary glomerulosclerosis.

A conceptual framework linking immunology, pathology, and clinical features in primary membranous nephropathy.

Primary membranous nephropathy is a leading cause of adult nephrotic syndrome. The field took a major step forward with the identification of phospholipase A2 receptor (PLA2R) as a target antigen in the majority of cases and with the ability to measure circulating autoantibodies to PLA2R. Since then, the existence of additional target antigens such as thrombospondin type-1 domain-containing 7A, exostosin 1 and 2, neural EGFL like 1, and semaphorin 3B has been demonstrated.

Collaborative Cohort of Cohorts for COVID-19 Research (C4R) Study: Study Design.

The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults at risk for coronavirus disease 2019 (COVID-19) comprising 14 established United States (US) prospective cohort studies. For decades, C4R cohorts have collected extensive data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R will link this pre-COVID phenotyping to information on SARS-CoV-2 infection and acute and post-acute COVID-related illness.

Control of Podocyte and Glomerular Capillary Wall Structure and Elasticity by WNK1 Kinase.

Cytoskeletal structure and its regulation are essential for maintenance of the differentiated state of specific types of cells and their adaptation to physiologic and pathophysiologic conditions. Renal glomerular capillaries, composed of podocytes, endothelial cells, and the glomerular basement membrane, have distinct structural and biophysical properties and are the site of injury in many glomerular diseases. Calcineurin inhibitors, immunosuppressant drugs used for organ transplantation and auto-immune diseases, can protect podocytes and glomerular capillaries from injury by preserving podocyte cytoskeletal structure.

T95 nucleophosmin phosphorylation as a novel mediator and marker of regulated cell death in acute kidney injury.

The function of site-specific phosphorylation of nucleophosmin (NPM), an essential Bax chaperone, in stress-induced cell death is unknown. We hypothesized that NPM threonine 95 (T95) phosphorylation both signals and promotes cell death. In resting cells, NPM exclusively resides in the nucleus and T95 is nonphosphorylated.

Loss of Roundabout Guidance Receptor 2 (Robo2) in Podocytes Protects Adult Mice from Glomerular Injury by Maintaining Podocyte Foot Process Structure.

Roundabout guidance receptor 2 (ROBO2) plays an important role during early kidney development. ROBO2 is expressed in podocytes, inhibits nephrin-induced actin polymerization, down-regulates nonmuscle myosin IIA activity, and destabilizes kidney podocyte adhesion. However, the role of ROBO2 during kidney injury, particularly in mature podocytes, is not known.

Coincidental crystalline light chain cast nephropathy, light chain proximal tubulopathy, and urine crystallopathy: A case report and review of the literature .

Plasma cell dyscrasias, including multiple myeloma (MM), are associated with diverse forms of pathology in the kidney. Some pathologic lesions, including light chain (myeloma) cast nephropathy (LCCN), are relatively common, while others, such as light chain proximal tubulopathy (LCPT), are less so. Both LCCN and LCPT are associated with clinical manifestations of acute kidney injury.

Segmentation of Glomeruli Within Trichrome Images Using Deep Learning.

Introduction: The number of glomeruli and glomerulosclerosis evaluated on kidney biopsy slides constitute standard components of a renal pathology report. Prevailing methods for glomerular assessment remain manual, labor intensive, and nonstandardized. We developed a deep learning framework to accurately identify and segment glomeruli from digitized images of human kidney biopsies.

Monoclonal IgG4/2κ Deposition Following Eculizumab Therapy for Recurrent Atypical Hemolytic Uremic Syndrome in Kidney Transplantation.

Eculizumab is an emerging therapy for atypical hemolytic uremic syndrome (aHUS). Early identification and treatment of recurrent aHUS after kidney transplantation requires a high clinical suspicion but results in improved graft function and patient outcome. We present a patient who developed recurrent aHUS after kidney transplantation that responded to eculizumab therapy.