Publications by authors named "Praga M"

The treatment landscape for IgA nephropathy (IgAN) is rapidly evolving with the introduction of novel therapies targeting diverse disease pathways. Some have already been approved in different countries, while others are under investigation in randomized controlled trials (RCTs) with encouraging results. However, almost all performed RCTs have included only patients with refractory non-nephrotic proteinuria and preserved renal function.

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  • The haemolytic uraemic syndromes (HUS) include various conditions, with some linked to complement activation (CaHUS).
  • The 2023 International Society of Nephrology HUS Forum featured experts discussing the latest knowledge, uncertainties, and proposed solutions in diagnosing and managing HUS.
  • Key areas needing research include naming conventions, complement testing, identifying biomarkers, genetic factors for aHUS, treatment strategies for C5 inhibitors, and improving access to care for patients.
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  • * Despite these positive outcomes, the effectiveness of SGLT2i in treating patients with glomerulonephritis remains uncertain due to various study limitations.
  • * This manuscript reviews evidence for the use of SGLT2i in glomerular diseases and discusses both the limitations and their potential clinical role.
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Background: Primary membranous nephropathy (PMN) is usually caused by anti-phospholipase A2 receptor (PLA2R) autoantibodies. There are different therapeutic options according to baseline risk. Novel biomarkers are needed to optimize risk stratification and predict and monitor the response to therapy, as proteinuria responses may be delayed.

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Membranous nephropathy (MN) management poses challenges, particularly in selecting appropriate immunosuppressive treatments (IST) and monitoring disease progression and complications. This article highlights 10 key tips for the management of primary MN based on current evidence and clinical experience. First, we advise against prescribing IST to patients without nephrotic syndrome (NS), emphasizing the need for close monitoring of disease progression.

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Randomized clinical trials are underway to evaluate the efficacy of novel agents targeting the alternative complement pathway in patients with C3 glomerulopathy (C3G), a rare glomerular disease. The Kidney Health Initiative convened a panel of experts in C3G to ( 1 ) assess the data supporting the use of the prespecified trial end points as measures of clinical benefit and ( 2 ) opine on efficacy findings they would consider compelling as treatment(s) of C3G in native kidneys. Two subpanels of the C3G Trial Endpoints Work Group reviewed the available evidence and uncertainties for the association between the three prespecified end points-( 1 ) proteinuria, ( 2 ) eGFR, and ( 3 ) histopathology-and anticipated outcomes.

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Background: Uncontrolled donation after circulatory death (uDCD) increases organ availability for kidney transplantation (KT) at the expense of a higher risk of primary graft nonfunction (PNF). At least half of the cases of PNF are secondary to graft venous thrombosis. The potential benefit from prophylactic anticoagulation in this scenario remains unclear.

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Background: Autosomal dominant Alport Syndrome (ADAS), also known as thin basement membrane disease (TBMD), is caused by pathogenic variants in the COL4A3 and COL4A4 genes. A cystic phenotype has been described in some patients with TBMD, but no genetic studies have been performed. We conducted a genetic and radiologic investigation in a cohort of ADAS patients to analyze the prevalence of multicystic kidney disease (MKD) and its association with chronic kidney disease (CKD).

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  • Complement 3 glomerulopathy (C3G) is a rare kidney disease caused by issues with the immune system, and iptacopan is being tested as a potential treatment in a study examining its effectiveness and safety.
  • In a phase 2 clinical trial with 27 patients, those with native C3G saw a 45% reduction in protein in their urine, while kidney transplant recipients had a significant decrease in C3 deposits in their biopsies after 84 days of treatment.
  • Overall, iptacopan showed promising results in improving kidney function and safety, as it normalized certain complement levels and had manageable side effects, with no reported deaths during the study.
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  • Immunoglobulin A nephropathy (IgAN) is the most common type of kidney inflammation globally, with recent research highlighting the critical role of the complement system, especially the alternative pathway, in its progression.
  • Studies indicate that specific proteins like factor H-related proteins and the lectin pathway contribute to disease severity, and glomerular deposition of markers like C3 and C4d may predict worse outcomes.
  • The understanding of complement's involvement in IgAN has led to the development of new treatments targeting various components of the complement system, with several clinical trials currently underway to assess their effectiveness.
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  • The PROTECT trial, a phase 3 study, evaluated the effectiveness of sparsentan, a dual receptor antagonist, in reducing proteinuria compared to irbesartan in patients with immunoglobulin A nephropathy over 110 weeks.* -
  • A total of 406 patients were randomly assigned to either sparsentan or irbesartan, with the primary goal being the change in proteinuria at 36 weeks and secondary goals related to kidney function and safety over the trial duration.* -
  • The findings from the trial, which included a significant reduction in proteinuria with sparsentan, provide important insights into potential treatment strategies for patients with kidney conditions.*
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  • The activation of the alternative pathway (AP) of the complement system plays a significant role in the development of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but the exact mechanisms are not fully understood.
  • Researchers analyzed gene variants and plasma levels of different complement components in a Spanish cohort of 102 AAV patients to explore the impact of the AP on the disease.
  • The study found that specific genetic variants influence disease susceptibility and kidney damage severity, while high levels of AP activation and certain plasma component ratios correlate with worse outcomes, highlighting FHR-1 as a potential therapeutic target.
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Membranous nephropathy (MN) is a pattern of injury caused by autoantibodies binding to specific target antigens, with accumulation of immune complexes along the subepithelial region of glomerular basement membranes. The past 20 years have brought revolutionary advances in the understanding of MN, particularly via the discovery of novel target antigens and their respective autoantibodies. These discoveries have challenged the traditional classification of MN into primary and secondary forms.

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Membranous nephropathy (MN) is a pattern of injury caused by autoantibodies binding to specific target antigens, with accumulation of immune complexes along the subepithelial region of glomerular basement membranes. The past 20 years have brought revolutionary advances in the understanding of MN, particularly via the discovery of novel target antigens and their respective autoantibodies. These discoveries have challenged the traditional classification of MN into primary and secondary forms.

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Introduction: We aimed to characterize the incidence and clinical presentation of membranous nephropathy (MN) after kidney transplantation (KT), and to assess allograft outcomes according to proteinuria rates and immunosuppression management.

Methods: Multicenter retrospective cohort study including patients from six Spanish centers who received a KT between 1991-2019. Demographic, clinical, and histological data were collected from recipients with biopsy-proven MN as primary kidney disease ( = 71) or MN diagnosed after KT ( = 4).

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Background: Up to 50-60% of patients with diabetes have non-diabetic kidney disease (NDKD) on kidney biopsy. Diabetic retinopathy (DR) is a microvascular complication of diabetes frequently associated with diabetic nephropathy (DN). The objective of the current study was to investigate the kidney outcomes and survival in patients with biopsy diagnoses of DN and NDKD according to the presence of DR.

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Lupus nephritis (LN) is the most frequent serious manifestation of patients with systemic lupus erythematosus (SLE). Up to 60% of SLE patients develop LN, which has a significant impact on their quality of life and prognosis. Recent advances have improved the diagnostic approach to LN, and new drugs that block specific pathways and kidney damage progression have been developed.

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Background: The role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the management glomerular/systemic autoimmune diseases with proteinuria in real-world clinical settings is unclear.

Methods: This is a retrospective, observational, international cohort study. Adult patients with biopsy-proven glomerular diseases were included.

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Introduction: Macroscopic hematuria (MH) bouts, frequently accompanied by acute kidney injury (AKI-MH) are one of the most common presentations of IgA nephropathy (IgAN) in the elderly. Immunosuppressive therapies are used in clinical practice; however, no studies have analyzed their efficacy on kidney outcomes.

Methods: This is a retrospective, multicenter study of a cohort of patients aged ≥50 years with biopsy-proven IgAN presenting with AKI-MH.

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A significant number of patients with systemic lupus erythematosus (between 20% and 60% according to different reported series) develop lupus nephritis in the course of its evolution, which directly influences their quality of life and vital prognosis. In recent years, the greater knowledge about the pathogenesis of systemic lupus and lupus nephritis has allowed relevant advances in the diagnostic approach and treatment of these patients, achieving the development of drugs specifically aimed at blocking key pathogenic pathways of the disease. Encouragingly, these immunomodulatory agents have shown in well-powered, randomized clinical trials good clinical efficacy in the medium-term, defined as proteinuria remission and preservation of kidney function, with an acceptable safety profile and good patient tolerability.

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Key Points: Kidney survival in C3 glomerulopathy is significantly higher in patients with a disease chronicity score <4 and proteinuria <3.5 g/d, regardless of baseline eGFR. A faster eGFR decline in C3 glomerulopathy is associated with higher probability of kidney failure.

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Significance Statement: Changes in albuminuria and GFR slope are individually used as surrogate end points in clinical trials of CKD progression, and studies have demonstrated that each is associated with treatment effects on clinical end points. In this study, the authors sought to develop a conceptual framework that combines both surrogate end points to better predict treatment effects on clinical end points in Phase 2 trials. The results demonstrate that information from the combined treatment effects on albuminuria and GFR slope improves the prediction of treatment effects on the clinical end point for Phase 2 trials with sample sizes between 100 and 200 patients and duration of follow-up ranging from 1 to 2 years.

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