Increased risk of kidney failure in patients with genetic kidney disorders.

BACKGROUNDIt is unknown whether the risk of kidney disease progression and failure differs between patients with and without genetic kidney disorders.METHODSThree cohorts were evaluated: the prospective Cure Glomerulonephropathy Network (CureGN) and 2 retrospective cohorts from Columbia University, including 5,727 adults and children with kidney disease from any etiology who underwent whole-genome or exome sequencing. The effects of monogenic kidney disorders and APOL1 kidney-risk genotypes on the risk of kidney failure, estimated glomerular filtration rate (eGFR) decline, and disease remission rates were evaluated along with diagnostic yields and the impact of American College of Medical Genetics secondary findings (ACMG SFs).

Myeloperoxidase-ANCA IgG induces different forms of small vessel vasculitis based on type of synergistic immune stimuli.

Anti-neutrophil cytoplasmic autoantibody (ANCA) vasculitis has diverse patterns of injury including microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Necrotizing and crescentic glomerulonephritis (NCGN) occurs in all syndromes and as renal limited vasculitis (RLV). Single-dose intravenous ANCA IgG-specific for mouse myeloperoxidase (MPO) causes RLV in mice.

Lupus nephritis kidney biopsy characteristics and preterm birth.

Individuals with lupus nephritis (LN) are at high risk of adverse maternal and fetal outcomes in pregnancy. Outside of pregnancy, proliferative lesions on kidney biopsies are associated with disease progression, but these have not been consistently associated with increased risk in pregnancy. This retrospective, single-center study examines how histologic findings, the timing from kidney biopsy to pregnancy, and the clinical features in the first trimester are associated with preterm birth among individuals with LN.

Examining the role of patient-reported external factors and risk of relapse in anti-neutrophilic cytoplasmic autoantibody vasculitis.

The role of stressors, insect bites, and infections on disease relapse of ANCA vasculitis has yet to be entirely explored, with limited retrospective studies focused on disease onset from small participant cohorts. Our study analyzes longitudinal survey data from 2011-2022 to evaluate this perspective from a large ANCA vasculitis cohort. We collected surveys every three to six months to obtain information on self-reported psychological stressors and significant life events, insect bites, and infections throughout clinical disease.

Acute Kidney Injury in Inflammatory Bowel Disease Patients: A Nationwide Comparative Analysis.

Rationale & Objective: About 25%-40% of patients with inflammatory bowel disease (IBD) may have extraintestinal manifestations, mainly involving the liver, skin, and joints. Kidney involvement in patients with IBD has been reported, but there are no estimates of its prevalence in population-based studies in the United States. We compared the frequency of acute kidney injury (AKI) among hospitalizations with IBD with that among hospitalizations with collagen vascular diseases and hospitalizations with neither condition.

Regulatory T cells effectively downregulate the autoimmune anti-MPO response and ameliorate anti-MPO induced glomerulonephritis in mice.

Regulation of autoreactive cells is key for both prevention and amelioration of autoimmune disease. A better understanding of the key cell population(s) responsible for downregulation of autoreactive cells would provide necessary foundational insight for cellular-based therapies in autoimmune disease. Utilizing a mouse model of anti-myeloperoxidase (MPO) glomerulonephritis, we sought to understand which immune cells contribute to downregulation of the anti-MPO autoimmune response.

Association of Obesity With Kidney and Cardiac Outcomes Among Patients With Glomerular Disease: Findings From the Cure Glomerulonephropathy Network.

Rationale & Objective: The influence of obesity on cardiorenal outcomes in individuals with glomerular disease is incompletely known. This study examined the association between obesity and kidney and cardiovascular outcomes in children and adults with glomerular kidney disease.

Study Design: Prospective, multicenter, observational study.

Influenza Vaccine Administration and Effectiveness Among Children and Adults With Glomerular Disease.

Introduction: Influenza infections contribute to excess healthcare utilization, morbidity, and mortality in individuals with glomerular disease (GD); however, influenza vaccination may not yield protective immune responses in this high-risk patient population. The objective of the present study was to describe influenza vaccine administration from 2010 to 2019 and explore the effectiveness of influenza vaccination in patients with GD.

Methods: We conducted an observational cohort study using healthcare claims for seasonal influenza vaccination (exposure) as well as influenza and influenza-like illness (outcomes) from commercially insured children and adults <65 years of age with primary GD in the Merative MarketScan Research Databases.

Infections Following Kidney Transplantation After Exposure to Immunosuppression for Treatment of Glomerulonephritis.

Rationale & Objective: Kidney transplant patients with glomerulonephritis (GN) as their native disease commonly have received pretransplant immunosuppression (PTI). This may contribute to the immunosuppression burden potentially increasing the risk for infections after transplantation.

Study Design: Single-center, retrospective cohort study.

Characterizing the metabolic response of the zebrafish kidney to overfeeding.

Obesity is a global epidemic and risk factor for the development of chronic kidney disease. Obesity induces systemic changes in metabolism, but how it affects kidney metabolism specifically is not known. Zebrafish have previously been shown to develop obesity-related kidney pathology and dysfunction when fed hypercaloric diets.

Kidney Disease Progression in Membranous Nephropathy among Black Participants with High-Risk APOL1 Genotype.

Background: Disparity in CKD progression among Black individuals persists in glomerular diseases. Genetic variants in the apolipoprotein L1 ( APOL1 ) gene in the Black population contribute to kidney disease, but the influence in membranous nephropathy remains unknown.

Methods: Longitudinally followed participants enrolled in the Glomerular Disease Collaborative Network or Cure Glomerulonephropathy Network were included if they had DNA or genotyping available for APOL1 (Black participants with membranous nephropathy) or had membranous nephropathy but were not Black.

Malignancy risk in kidney transplant recipients exposed to immunosuppression pre-transplant for the treatment of glomerulonephritis.

Background: Kidney transplant patients with glomerulonephritis (GN) as their native disease may receive significant amounts of pre-transplant immunosuppression (PTI), which could increase the risk for development of malignancy post-transplant.

Methods: We conducted a single-center, retrospective study of kidney transplant recipients from January 2005 until May 2020. Patients with GN as their native kidney disease who received PTI for treatment of GN (n = 184) were compared with a control cohort (n = 579) of non-diabetic, non-PTI-receiving kidney transplant patients.

Relevance of Combined Clinicopathologic Phenotype and Antineutrophil Cytoplasmic Autoantibody Serotype in the Diagnosis of Antineutrophil Cytoplasmic Autoantibody Vasculitis.

Introduction: Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), 2 major clinicopathologic variants of antineutrophil cytoplasmic autoantibody (ANCA) vasculitides, are mostly associated with proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA, respectively. Less is known regarding the uncommon forms of ANCA vasculitis, PR3-ANCA MPA and MPO-ANCA GPA.

Methods: In this cohort study we detailed the clinical presentation and outcome of patients with PR3-ANCA MPA and MPO-ANCA GPA from the Glomerular Disease Collaborative Network (GDCN) inception cohort.

The frequency of Treg subsets distinguishes disease activity in ANCA vasculitis.

Objectives: T regulatory cells (Tregs) are a heterogeneous group of immunoregulatory cells that dampen self-harming immune responses and prevent the development of autoimmune diseases. In anti-neutrophil cytoplasmic autoantibody (ANCA) vasculitis, Tregs possess diminished suppressive capacity, which has been attributed to the expression of a FOXP3 splice-variant lacking exon 2 in T cells (FOXP3Δ2 CD4 T cells). However, the suppressive capacity of Tregs varies between subsets.

Glomerular Hematuria and the Utility of Urine Microscopy: A Review.

Evaluation of hematuria and microscopic examination of urine sediment are commonly used tools by nephrologists in their assessment of glomerular diseases. Certain morphological aspects of urine red blood cells (RBCs) seen by microscopy may help in identifying the source of hematuria as glomerular or not. Recognized signs of glomerular injury are RBC casts or dysmorphic RBCs, in particular acanthocytes (ring-shaped RBCs with protruding blebs).

Immunological Interaction of HLA-DPB1 and Proteinase 3 in ANCA Vasculitis is Associated with Clinical Disease Activity.

Background: PR3-ANCA vasculitis has a genetic association with HLA-DPB1. We explored immunologic and clinical features related to the interaction of HLA-DPB1*04:01 with a strongly binding PR3 peptide epitope (PR3).

Methods: Patients with ANCA vasculitis with active disease and disease in remission were followed longitudinally.

Mechanisms of vascular damage in ANCA vasculitis.

The discovery of anti-neutrophil cytoplasmic antibodies (ANCA) and their antigenic targets, myeloperoxidase (MPO) and proteinase 3 (PR3), has led to further understanding as to the pathophysiologic processes that underlie vascular and tissue damage in ANCA vasculitis. ANCA trigger neutrophil activation leading to vascular damage in ANCA vasculitis. However, decades of study have determined that neutrophil activation alone is not sufficient to cause disease.

High-calorie diet results in reversible obesity-related glomerulopathy in adult zebrafish regardless of dietary fat.

Obesity is a risk factor for the development of kidney disease. The role of diet in this association remains undetermined, in part due to practical limitations in studying nutrition in humans. In particular, the relative importance of calorie excess versus dietary macronutrient content is poorly understood.

Association of Lupus Nephritis Histopathologic Classification With Venous Thromboembolism-Modification by Age at Biopsy.

Introduction: Lupus nephritis (LN) is an independent risk factor for venous thromboembolism (VTE). The risk of VTE has not been analyzed by International Society of Nephrology/Renal Pathology Society or World Health Organization LN class. Study goals were to measure VTE incidence in an LN patient cohort, to evaluate associations between VTE and LN class, and to investigate factors modifying associations between VTE and LN class.

Treatment Updates in Antineutrophil Cytoplasmic Autoantibodies (ANCA) Vasculitis.

ANCA vasculitis is a small-vessel vasculitis (SVV) resulting in inflammation of small- and medium-sized blood vessels. Since the initial description of SVV, there have been tremendous advances in our understanding of its pathogenesis. Over the last decade, we have made significant progress in understanding the pathogenesis and improving the treatment and prognosis of patients with ANCA vasculitis.