ClC-Kb pore mutation disrupts glycosylation and triggers distal tubular remodeling.

Mutations in the CLCNKB gene (1p36), encoding the basolateral chloride channel ClC-Kb, cause type 3 Bartter syndrome. We identified a family with a mixed Bartter/Gitelman phenotype and early-onset kidney failure and by employing a candidate gene approach, identified what we believe is a novel homozygous mutation (CLCNKB c.499G>T [p.

Spatial analysis reveals targetable macrophage-mediated mechanisms of immune evasion in hepatocellular carcinoma minimal residual disease.

Hepatocellular carcinoma (HCC) frequently recurs from minimal residual disease (MRD), which persists after therapy. Here, we identified mechanisms of persistence of residual tumor cells using post-chemoembolization human HCC (n = 108 patients, 1.07 million cells) and a transgenic mouse model of MRD.

Esm-1 mediates transcriptional polarization associated with diabetic kidney disease.

Esm-1, endothelial cell-specific molecule-1, is a susceptibility gene for diabetic kidney disease (DKD) and is a secreted proteoglycan, with notable expression in kidney, which attenuates inflammation and albuminuria. However, little is known about expression in mature tissues in the presence or absence of diabetes. We utilized publicly available single-cell RNA sequencing data to characterize expression in 27,786 renal endothelial cells (RECs) obtained from three mouse and four human databases.

Liver Pathology After Hematopoietic Stem Cell Transplantation.

Hematopoietic stem cell transplantation is used to treat a variety of hematologic malignancies and autoimmune conditions. The immunosuppressive medications as well as other therapies used both before and after transplantation leave patients susceptible to a wide spectrum of complications, including liver injury. Causes for liver damage associated with stem cell transplantation include sinusoidal obstruction syndrome, graft-versus-host disease, iron overload, and opportunistic infection.

Non-Full House Membranous Lupus Nephritis Represents a Clinically Distinct Subset.

Key Points: Non-full house (NFH) membranous lupus nephritis (MLN) is a minor subset of all MLN cases. Patients with NFH MLN tend to be older when diagnosed with systemic lupus erythematosus, undergo first renal biopsy at an older age, and have fewer extrarenal systemic manifestations. Lower load of C3 glomerular deposits seen in NFH MLN biopsies suggests attenuation of complement-mediated injury, which may have wider systemic implications.

Immunoglobulin G4-Seronegative Autoimmune Cholangiopathy With Pancreatic and Hepatic Involvement Mimicking as Primary Sclerosing Cholangitis.

Immunoglobulin G4-seronegative autoimmune cholangiopathy is a rare cause of biliary strictures. We describe a 27-year-old man presenting with elevated liver enzymes, recurrent cholangitis/bacteremia, biliary strictures, and normal immunoglobulin G4 levels, who was initially diagnosed with primary sclerosing cholangitis, and later listed for transplantation for recurrent bacteremia. Subsequent surveillance imaging demonstrated morphologic changes consistent with biliary strictures and autoimmune pancreatitis.

Renal improvement and remission in a patient with refractory ANCA-associated vasculitis treated with avacopan.

Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis is associated with end-organ damage resulting in significant morbidity and mortality. Most recently, avacopan, an orally administered selective antagonist of the C5a receptor, was approved by the US Food and Drug Administration as an adjunctive treatment of adult patients with severe, active ANCA-associated vasculitis (granulomatosis with polyangiitis and microscopic polyangiitis) in combination with standard therapy including glucocorticoids. This case study describes a 58-year-old Asian female with severe ANCA-associated vasculitis and acute renal failure who responded to adjunctive therapy with avacopan despite being refractory to rituximab and glucocorticoid therapy.

Esm-1 mediates transcriptional polarization associated with diabetic kidney disease.

Background: Esm-1, endothelial cell-specific molecule-1, is a susceptibility gene for diabetic kidney disease (DKD) and is a cytokine- and glucose-regulated, secreted proteoglycan, that is notably expressed in kidney and attenuates inflammation and albuminuria. has restricted expression at the vascular tip during development but little is known about its expression pattern in mature tissues, and its precise effects in diabetes.

Methods: We utilized publicly available single-cell RNA sequencing data to explore the characteristics of expression in 27,786 renal endothelial cells obtained from four adult human and three mouse databases.

pSTAT1 Is Activated during the Progression of IgA Nephropathy.

Introduction: IgA nephropathy is the most common primary glomerular disease. Its pathogenesis is still poorly understood. Alterations of the Janus kinase signal transducer and activator of transcription (JAK-STAT) pathway may play an important role in IgA nephropathy.

Immunoregulatory effects of RGMb in gut inflammation.

Graft-versus-host disease (GvHD) is a major complication after allogeneic hematopoietic cell transplantation (HCT). Current strategies to prevent GvHD with immunosuppressive drugs carry significant morbidity and may affect the graft-versus-tumor (GVT) effect. Inflammatory bowel disease (IBD) is an intestinal inflammatory condition that affects more than 2 million people in the United States.

Clinicopathologic features of non-lupus membranous nephropathy in a pediatric population.

Background: Membranous nephropathy is an uncommon cause of nephrotic syndrome in pediatrics.

Methods: We reviewed our kidney biopsy records for patients ≤ 20 years of age with membranous nephropathy without evidence of systemic lupus erythematosus within 6 months of biopsy (January 1995-September 2020). Staining for PLA2R, NELL1, THSD7A, SEMA3B, EXT2 (3 biopsies), and IgG-subclass were performed.

A Diverse Spectrum of Immune Complex- and Complement-Mediated Kidney Diseases Is Associated With Mantle Cell Lymphoma.

Introduction: There are limited reports on kidney biopsy findings in patients with mantle cell lymphoma (MCL).

Methods: We initiated a multi-institutional, retrospective review of kidney biopsy findings in patients with active and treated MCL.

Results: A total of 30 patients with MCL and kidney biopsies were identified, with a median age of 67 (range 48-87) years, 73% of whom were men.

Pregnancy and severely reduced renal mass: A stress model showing renal hyperfiltration.

Pregnancy may increase signs of renovascular stress. We compared pregnant sham operated (S) and 5/6 nephrectomy (NX) rats to examine the effect of pregnancy on reduced nephron number. Blood pressure (BP), heart rate (HR), body weight (BW), food/water intake, serum creatinine (Cr), urinalyses were assessed weekly, and end pregnancy renal histology examined.

Invariant natural killer T-cell subsets have diverse graft-versus-host-disease-preventing and antitumor effects.

Invariant natural killer T (iNKT) cells are a T-cell subset with potent immunomodulatory properties. Experimental evidence in mice and observational studies in humans indicate that iNKT cells have antitumor potential as well as the ability to suppress acute and chronic graft-versus-host-disease (GVHD). Murine iNKT cells differentiate during thymic development into iNKT1, iNKT2, and iNKT17 sublineages, which differ transcriptomically and epigenomically and have subset-specific developmental requirements.

Impact of Bridging Locoregional Therapies for Hepatocellular Carcinoma on Post-transplant Clinical Outcome.

Long waiting times due to ongoing organ shortage have led to increased utilization of locoregional therapies (LRTs) to bridge patients with hepatocellular carcinoma (HCC) to liver transplantation (LT). We performed this study to evaluate the impact of LRTs on post-LT outcomes. We conducted a retrospective study of patients who were transplanted for HCC at Stanford University Hospital between 2008 and 2018 (n = 302).

Multicenter Clinicopathologic Correlation of Kidney Biopsies Performed in COVID-19 Patients Presenting With Acute Kidney Injury or Proteinuria.

Rationale & Objective: Kidney biopsy data inform us about pathologic processes associated with infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We conducted a multicenter evaluation of kidney biopsy findings in living patients to identify various kidney disease pathology findings in patients with coronavirus disease 2019 (COVID-19) and their association with SARS-CoV-2 infection.

Study Design: Case series.

Progression of proliferative glomerulonephritis with monoclonal IgG deposits in pediatric patients.

Background: Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) is a glomerular disease defined by non-organized glomerular deposits of heavy and light chain-restricted immunoglobulin and is rarely reported in children.

Methods: We characterized a series of nine pediatric patients from two academic centers with biopsy-proven PGNMID and additionally describe two patients with monotypic IgG in the setting of IgM deposition.

Results: Each patient presented with hematuria and/or proteinuria; however, only five had elevated serum creatinine.

Membranous nephropathy in patients with HIV: a report of 11 cases.

Background: Membranous nephropathy (MN) has been recognized to occur in patients with human immunodeficiency virus (HIV) infection since the beginning of the HIV epidemic. The prevalence of phospholipase A2 receptor (PLA2R)-associated MN in this group has not been well studied.

Methods: We conducted a retrospective review of electronic pathology databases at three institutions to identify patients with MN and known HIV at the time of renal biopsy.

Gastrointestinal Eosinophil Responses in a Longitudinal, Randomized Trial of Peanut Oral Immunotherapy.

Background & Aims: Gastrointestinal side effects are common during oral immunotherapy (OIT) and eosinophilic esophagitis (EoE) is a potential complication. We aimed to characterize eosinophilic gastrointestinal responses to peanut OIT, in which peanut protein is given orally, with incremental increases in dose over time.

Methods: Twenty adults with IgE-mediated peanut allergy were randomly assigned to groups given peanut OIT (n = 15) or placebo (n = 5); 1 additional subject withdrew before randomization.

Myelin bodies in LMX1B-associated nephropathy: potential for misdiagnosis.

Background: Myelin figures, or zebra bodies, seen on electron microscopy were historically considered pathognomonic of Fabry disease, a rare lysosomal storage disorder caused by alpha-galactosidase A deficiency and associated with X-linked recessive mode of inheritance. More recently, iatrogenic phospholipidosis has emerged as an important alternate cause of myelin figures in the kidney.

Methods: We report two families with autosomal dominant nephropathy presenting with proteinuria and microscopic hematuria, and the kidney biopsies were notable for the presence of myelin figures and zebra bodies.