Histologic and Clinical Factors Associated with Kidney Outcomes in IgA Vasculitis Nephritis.

Background: Nephritis is a common manifestation of IgA vasculitis and is morphologically indistinguishable from IgA nephropathy. While MEST-C scores are predictive of kidney outcomes in IgA nephropathy, their value in IgA vasculitis nephritis has not been investigated in large multiethnic cohorts.

Methods: Biopsies from 262 children and 99 adults with IgA vasculitis nephritis ( N =361) from 23 centers in North America, Europe, and Asia were independently scored by three pathologists.

Expanding options of supportive care in IgA nephropathy.

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, with a potentially serious prognosis. At present, management of IgAN is primarily based on therapeutic lifestyle changes, and excellent blood pressure control and maximized supportive treatment with the combination of inhibition of the renin-angiotensin-aldosterone system with either inhibitors of angiotensin-converting enzyme or angiotensin II receptor blockers and inhibitors of sodium-glucose cotransporter-2, and possibly in the future also with endothelin antagonists. Supportive care currently represents the cornerstone of treatment of IgAN.

Clinical Features, Outcomes, and Response to Corticosteroid Treatment of Acute Tubulointerstitial Nephritis: A Single-Centre Retrospective Cohort Study in the Czech Republic.

Introduction: Acute tubulointerstitial nephritis (ATIN) is a well-recognized cause of acute kidney injury (AKI) due to the tubulointerstitial inflammation. The aim of this study was to explore the clinical features, outcomes, and responses to corticosteroid treatment in patients with ATIN.

Methods: Patients with biopsy-proven ATIN, who were diagnosed between 1994 and 2016 at the Department of Nephrology, Charles University, First Faculty of Medicine, and General University Hospital in Prague, were included in the study.

Novel transcriptomic signatures associated with premature kidney allograft failure.

Background: The power to predict kidney allograft outcomes based on non-invasive assays is limited. Assessment of operational tolerance (OT) patients allows us to identify transcriptomic signatures of true non-responders for construction of predictive models.

Methods: In this observational retrospective study, RNA sequencing of peripheral blood was used in a derivation cohort to identify a protective set of transcripts by comparing 15 OT patients (40% females), from the TOMOGRAM Study (NCT05124444), 14 chronic active antibody-mediated rejection (CABMR) and 23 stable graft function patients ≥15 years (STA).

Unique Biomarkers of Collagen Type III Remodeling Reflect Different Information Regarding Pathological Kidney Tissue Alterations in Patients with IgA Nephropathy.

Kidney fibrosis is the hallmark of chronic kidney disease (CKD) and is characterized by an imbalanced extracellular matrix (ECM) remodeling. Collagen type III is one of the main ECM components of the interstitial matrix of the kidney. We hypothesized that measuring three biomarkers of collagen type III reflecting different aspects of this protein turnover (C3M, C3C, and PRO-C3) may provide different information about the fibrotic burden in patients with IgA nephropathy (IgAN).

Serum and Urine Biomarkers Related to Kidney Fibrosis Predict Kidney Outcome in Czech Patients with IgA Nephropathy.

We evaluated biomarkers related to kidney fibrosis for the outcome of patients with IgA nephropathy (IgAN). Clinical parameters (estimated glomerular filtration rate, hypertension, proteinuria) and histological findings were assessed in 134 patients with IgAN at the time of diagnosis and followed up prospectively (mean follow-up time, 56.5 months).

New Treatment Strategies for IgA Nephropathy: Targeting Plasma Cells as the Main Source of Pathogenic Antibodies.

Immunoglobulin A nephropathy (IgAN) is a rare autoimmune disorder and the leading cause of biopsy-reported glomerulonephritis (GN) worldwide. Disease progression is driven by the formation and deposition of immune complexes composed of galactose-deficient IgA1 (Gd-IgA1) and Gd-IgA1 autoantibodies (anti-Gd-IgA1 antibodies) in the glomeruli, where they trigger complement-mediated inflammation that can result in loss of kidney function and end-stage kidney disease (ESKD). With the risk of progression and limited treatment options, there is an unmet need for therapies that address the formation of pathogenic Gd-IgA1 antibody and anti-Gd-IgA1 antibody-containing immune complexes.

Outcome of 313 Czech Patients With IgA Nephropathy After Renal Transplantation.

The recurrence of IgA nephropathy (IgAN) after kidney transplantation occurs in 20-35% of patients. The main aim of this study is to evaluate risk factors affecting the course of IgAN after renal biopsy of native kidney and kidney transplant. We evaluated clinical parameters and histological findings at the time of biopsy of native kidney and after kidney transplantation in 313 patients with IgAN with a follow-up of up to 36 years.

Endotrophin, a collagen type VI-derived matrikine, reflects the degree of renal fibrosis in patients with IgA nephropathy and in patients with ANCA-associated vasculitis.

Background: Renal fibrosis is the hallmark of chronic kidney disease (CKD) and is characterized by an imbalanced extracellular matrix remodelling. Endotrophin (ETP) is a signalling molecule released from collagen type VI (COL VI). ETP can be measured by the PRO-C6 assay, which quantifies the levels of COL VI formation.

Urine proteomics for prediction of disease progression in patients with IgA nephropathy.

Background: Risk of kidney function decline in immunoglobulin A (IgA) nephropathy (IgAN) is significant and may not be predicted by available clinical and histological tools. To serve this unmet need, we aimed at developing a urinary biomarker-based algorithm that predicts rapid disease progression in IgAN, thus enabling a personalized risk stratification.

Methods: In this multicentre study, urine samples were collected in 209 patients with biopsy-proven IgAN.

Emerging Modes of Treatment of IgA Nephropathy.

IgA nephropathy is the most common primary glomerulonephritis with potentially serious outcome leading to end stage renal disease in 30 to 50% of patients within 20 to 30 years. Renal biopsy, which might be associated with risks of complications (bleeding and others), still remains the only reliable diagnostic tool for IgA nephropathy. Therefore, the search for non-invasive diagnostic and prognostic markers for detection of subclinical types of IgA nephropathy, evaluation of disease activity, and assessment of treatment effectiveness, is of utmost importance.

Does the renal expression of Toll-like receptors play a role in patients with IgA nephropathy?

The onset of IgA nephropathy (IgAN), characterized by glomerular deposition of IgA-containing immune complexes, is often associated with synpharyngitic hematuria. Innate immune responses mediated by Toll-like receptors (TLR) may play a role in IgAN onset and/or progression. Here, we assessed the expression of TLR 4, 7, 8, and 9 in renal-biopsy specimens from patients with IgAN, with different degree of proteinuria and eGFR, compared with normal-kidney and disease-control tissues (ANCA-associated vasculitis).

Correction: Galactose-deficient IgA1 and the corresponding IgG autoantibodies predict IgA nephropathy progression.

[This corrects the article DOI: 10.1371/journal.pone.

Galactose-deficient IgA1 and the corresponding IgG autoantibodies predict IgA nephropathy progression.

Background: IgA nephropathy (IgAN), the most common primary glomerulonephritis worldwide, has serious outcomes with end-stage renal disease developing in 30-50% of patients. The diagnosis requires renal biopsy. Due to its inherent risks, non-invasive approaches are needed.

Defective gene expression of the membrane complement inhibitor CD46 in patients with progressive immunoglobulin A nephropathy.

Background: Complement is thought to play a role in immunoglobulin A nephropathy (IgAN), though the activating mechanisms are unknown. This study focused on the gene expression of CD46 and CD55, two key molecules for regulating C3 convertase activity of lectin and alternative complement pathways at a cellular level.

Methods: The transcriptional expression in peripheral white blood cells (WBCs) of CD46 and CD55 was investigated in 157 patients enrolled by the Validation of the Oxford Classification of IgAN group, looking for correlations with clinical and pathology features and estimated glomerular filtration rate (eGFR) modifications from renal biopsy to sampling.

Molecular profiling in IgA nephropathy and focal and segmental glomerulosclerosis.

The aim of the study was to characterize by molecular profiling two glomerular diseases: IgA nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS) and to identify potential molecular markers of IgAN and FSGS progression. The expressions of 90 immune-related genes were compared in biopsies of patients with IgAN (n=33), FSGS (n=17) and in controls (n=11) using RT-qPCR. To identify markers of disease progression, gene expression was compared between progressors and non-progressors in 1 year follow-up.

Proteomic approach for identification of IgA nephropathy-related biomarkers in urine.

Proteinuria is often used as a surrogate marker in monitoring and predicting outcome in patients with chronic kidney diseases, but it is non-specific. IgAN belongs to the most common primary glomerulonephritis worldwide with serious prognosis. The main aim of this work was to assess differences in urine proteins in patients with IgA nephropathy and to identify abnormal proteins as potential biomarkers of IgA nephropathy or the renal disease.

Toward Noninvasive Diagnosis of IgA Nephropathy: A Pilot Urinary Metabolomic and Proteomic Study.

IgA nephropathy is diagnosed by renal biopsy, an invasive procedure with a risk of significant complications. Noninvasive approaches are needed for possible diagnostic purposes and especially for monitoring disease activity or responses to treatment. In this pilot project, we assessed the utility of urine samples as source of biomarkers of IgA nephropathy.

Risk factors for progression in children and young adults with IgA nephropathy: an analysis of 261 cases from the VALIGA European cohort.

Background: There is a need for early identification of children with immunoglobulin A nephropathy (IgAN) at risk of progression of kidney disease.

Methods: Data on 261 young patients [age <23 years; mean follow-up of 4.9 (range 2.

Markers for the progression of IgA nephropathy.

We have summarized the latest findings on markers for progression of immunoglobulin A (IgA) nephropathy (IgAN), the most common primary glomerulonephritis with a high prevalence among end-stage renal disease (ESRD) patients. The clinical predictors of renal outcome in IgAN nephropathy, such as proteinuria, hypertension, and decreased estimated glomerular filtration rate (eGFR) at the time of the diagnosis, are well known. The Oxford classification of IgAN identified four types of histological lesions (known as the MEST score) associated with the development of ESRD and/or a 50 % reduction in eGFR.