Detailed Pathophysiology of Minimal Change Disease: Insights into Podocyte Dysfunction, Immune Dysregulation, and Genetic Susceptibility DOI Open Access

Maja Roman,

Michał Nowicki

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(22), С. 12174 - 12174

Опубликована: Ноя. 13, 2024

Minimal Change Disease (MCD) is a predominant cause of idiopathic nephrotic syndrome in the pediatric population, yet presents significant clinical challenges due to its frequent relapses and steroid resistance. Despite relatively benign histological appearance, MCD characterized by severe proteinuria, hypoalbuminemia, edema, which may affect patient outcomes. Current treatment strategies primarily rely on corticosteroids, are effective inducing remission but associated with high relapse rates, resistance, numerous long-term side effects, underscoring need for more targeted therapeutic approaches. This narrative review synthesizes current knowledge pathophysiological mechanisms underlying MCD, focusing following three critical areas: podocyte dysfunction, immune dysregulation, genetic susceptibility. Podocyte particularly involving alterations nephrin, plays central role breakdown glomerular filtration barrier, leading characteristic proteinuria observed MCD. Immune including presence autoantibodies against nephrin other components, exacerbates injury contributes disease progression, suggesting an autoimmune component disease. Genetic factors, mutations NPHS1 NPHS2 genes, have been identified as contributors susceptibility, influencing variability response overall severity. Understanding these crucial developing therapies that address causes rather than merely managing symptoms. highlights further research into processes pave way personalized strategies, ultimately improving outcomes reducing reliance corticosteroids.

Язык: Английский

Membranous nephropathy: pathogenesis and treatments DOI Creative Commons

M.M. Wang,

Jingjuan Yang,

Xin Fang

и другие.

MedComm, Год журнала: 2024, Номер 5(7)

Опубликована: Июнь 29, 2024

Abstract Membranous nephropathy (MN), an autoimmune disease, can manifest at any age and is among the most common causes of nephrotic syndrome in adults. In 80% cases, specific etiology MN remains unknown, while remaining cases are linked to drug use or underlying conditions like systemic lupus erythematosus, hepatitis B virus, malignancy. Although about one‐third patients may achieve spontaneous complete partial remission with conservative management, another third face elevated risk disease progression, potentially leading end‐stage renal within 10 years. The identification phospholipase A2 receptor as primary target antigen has brought a significant shift management monitoring. This review explores recent advancements pathophysiology MN, encompassing pathogenesis, clinical presentations, diagnostic criteria, treatment options, prognosis, focus on emerging developments pathogenesis therapeutic strategies aimed halting progression. By synthesizing latest research findings insights, this seeks contribute ongoing efforts enhance our understanding challenging disorder.

Язык: Английский

Процитировано

5
METTL10 attenuates adriamycin-induced podocyte injury by targeting cell dedifferentiation DOI Creative Commons

Jiwen Bao,

Z Li,

Huanzhen Yao

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 7, 2025

Chronic kidney disease (CKD) is a worldwide public health problem. Podocyte damage hallmark of glomerular diseases including focal segmental glomerulosclerosis (FSGS) and one the leading causes CKD. Lysine methylation crucial post-translational modification. Beyond epidemic regulation, various lysine methyltransferases have been recently reported to participate in progression, cancers diseases. Among them, Methyltransferase-like 10 (METTL10), recognized as gene associated with estimated filtration rate (eGFR) CKD risk. However, its role podocyte remains unclear. We identified differentially expressed genes(DEGs)in injury by bioinformatics analysis. Patients diagnosed idiopathic FSGS renal biopsy were enrolled. Mouse model was established Adriamycin(ADR) urinary albumin/ creatinine ratio(UACR) detected. Murine cell line stimulated ADR. determined METTL10 significantly downregulated genes damaged podocytes, confirmed decreased expression patients mice ADR-induced nephrosis, respectively. Moreover, we found negative correlation between levels UACR mice. reduced ADR-treated accompanied dedifferentiation (loss synaptopodin, podocin, nephrin, WT-1) acquisition mesenchymal markers (snail, desmin, pax2). Knockdown promoted their dedifferentiation. regulates under damaging stimuli protects podocytes.

Язык: Английский

Процитировано

0
Current understanding of adult nephrotic syndrome: Minimal change disease DOI
Krishna Kumar Govindarajan

World Journal of Nephrology, Год журнала: 2025, Номер 14(1)

Опубликована: Янв. 18, 2025

The underlying molecular changes that result in minimal change disease (nephrotic syndrome) require an in-depth analysis. Current studies have shown the involvement of zinc fingers and homeobox transcriptional factors its pathogenesis. application therapeutic drugs relies on understanding cascade events to determine their efficacy managing clinical condition.

Язык: Английский

Процитировано

0
Targeting endoplasmic reticulum stress: an innovative therapeutic strategy for podocyte-related kidney diseases DOI Creative Commons
Jiao Lv, Haiying Yu, Shaojun Du

и другие.

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Янв. 21, 2025

The endoplasmic reticulum (ER) is a vital organelle responsible for protein quality control, including the folding, modification, and transport of proteins. When misfolded or unfolded proteins accumulate in ER, it triggers stress (ERS) activates response (UPR) to restore ER homeostasis. However, prolonged excessive ERS can lead apoptosis. kidneys play crucial role maintaining physiological functions by excreting metabolic waste, regulating blood volume, balancing electrolytes acid-base levels, secreting various bioactive substances. Podocytes, epithelial cells situated outside glomerular basement membrane, are essential structural integrity permeability filtration barrier. Previous studies have shown that podocytes contribute development diseases such as glomerulonephritis, hereditary nephropathy, diabetic kidney disease, potentially progressing end-stage renal disease causing patient mortality. As such, investigating has become key area focus research. This study examines recent advancements understanding effects on across diseases, highlights podocyte progression, explores potential therapeutic benefits targeting UPR manage thereby providing scientific basis clinical interventions.

Язык: Английский

Процитировано

0
Membranous Nephropathy Target Antigens Display Podocyte-Specific and Non-Specific Expression in Healthy Kidneys DOI Open Access
Ying Dong, Hui Xu, Damu Tang

и другие.

Genes, Год журнала: 2025, Номер 16(3), С. 241 - 241

Опубликована: Фев. 20, 2025

Background/Objectives: Autoimmunity towards podocyte antigens causes membranous nephropathy (MN). Numerous MN target (MNTAgs) have been reported, including PLA2R1, THSD7A, NTNG1, TGFBR3, HTRA1, NDNF, SEMA3B, FAT1, EXT1, CNTN1, NELL1, PCDH7, EXT2, PCSK6, and NCAM1, but their expression has not thoroughly studied. Methods: We screened CZ CELLxGene single-cell RNA (scRNA) sequence datasets for those of adult, fetal, mouse kidneys analyzed the above MNTAgs’ expression. Results: In adult kidneys, most MNTAgs are present in podocytes, except PCSK6 NCAM1. PLA2R1 is expressed significantly more than other podocytes a major marker, consistent with as dominant MNTAg. Additionally, top-upregulated gene chronic kidney disease, acute injury, diabetic nephropathy, indicating its general role causing injury. NDNF display podocyte-enriched along elevated chromatin accessibility suggesting transcription initiation contributing to preference podocytes. fetal kidney, While weakly SEMA3B abundantly immature mature supporting childhood Thsd7a only MNTAg prominent level podocyte-specific Conclusions: Most adults during renal development. adults, highly enriched upregulated multiple diseases accompanied by proteinuria. specifically at an level.

Язык: Английский

Процитировано

0
The Spectrum of Minimal Change Disease/Focal Segmental Glomerulosclerosis: From Pathogenesis to Proteomic Biomarker Research DOI Open Access

Yuriy Maslyennikov,

Andrada Alina Bărar, Crina Claudia Rusu

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(6), С. 2450 - 2450

Опубликована: Март 9, 2025

Podocyte injury plays a central role in both focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD). Pathogenic mechanisms are diverse incompletely understood, partially overlap between FSGS MCD, not reflected by kidney biopsy. In order to optimize the current variable response treatment, personalized management should rely on pathogenesis. One promising approach involves identifying biomarkers associated with specific pathogenic pathways. With advancement of technology, proteomic studies could be valuable tool improve knowledge this area define valid biomarkers, as they have other areas glomerular disease. This work attempts cover discuss main podocyte injury, followed review recent literature biomarker podocytopathies. Most these been conducted biofluids, while tissue applied podocytopathies remain limited. While we recognize importance non-invasive biofluid propose sequential for their development: proteomics first identify proteins increased expression that may reflect underlying mechanisms; subsequently, validation urine or plasma pave way diagnostic prognostic biomarker-based approach.

Язык: Английский

Процитировано

0
The Power of Antibodies: Advancing Biomarker-Based Disease Detection and Surveillance DOI
Woei Kean Ng,

Gunasegran Thanusha,

Pei Pei Chong

и другие.

Immunological Investigations, Год журнала: 2025, Номер unknown, С. 1 - 25

Опубликована: Апрель 21, 2025

Antibodies have long served as fundamental tools in disease diagnosis and surveillance. Their utility biomarkers has expanded beyond infectious diseases to encompass a wide range of health conditions. This review aims explore recent advancements antibody biomarker discovery their applications diagnosing monitoring diverse It also examines the role surveillance public epidemiological studies. A comprehensive analysis literature was conducted, focusing on studies that identify characterize disease-specific antibodies. Particular attention given relevance autoimmune diseases, infections, cancers, neurological disorders. The highlights clinical significance. discusses challenges antibody-based assessing prevalence, tracking immunity trends, supporting One Health strategies. Recent demonstrate significant potential improving early diagnosis, personalized treatment, population-level management. Antibody continues play pivotal guiding responses understanding dynamics.

Язык: Английский

Процитировано

0
From diagnosis to treatment of minimal change disease in pregnancy DOI
Petra Bolt,

I Adamovic,

Matija Horaček

и другие.

CEN Case Reports, Год журнала: 2025, Номер unknown

Опубликована: Май 5, 2025

Язык: Английский

Процитировано

0
The intelligent podocyte: sensing and responding to a complex microenvironment DOI
John F. Bertram, Luise A. Cullen‐McEwen, Vinícius Andrade‐Oliveira

и другие.

Nature Reviews Nephrology, Год журнала: 2025, Номер unknown

Опубликована: Май 8, 2025

Язык: Английский

Процитировано

0
Sanqi oral solution alleviates podocyte apoptosis in experimental membranous nephropathy by mediating EMT through the ERK/CK2-α/β-catenin pathway DOI Creative Commons
Xiaowan Wang, Juanjuan Wang,

Bidan Zheng

и другие.

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Май 9, 2025

Introduction Sanqi oral solution (SQ) is a Chinese medicine that has been used well to treat idiopathic membranous nephropathy (IMN). It demonstrated mitigate IMN proteinuria by inhibiting podocyte apoptosis. however, the precise mechanism not fully elucidated. Methods A passive Heymann (PHN) rat model was mimic in vivo disease characteristics of IMN. The PHN rats were intragastrically administered SQ (12.6/6.3 mL/kg) or tacrolimus (0.315 mg/kg) for 21 days. applied ADR-induced podocytes vitro . effects on and its underlying mechanisms determined measuring biochemical indices, pathomorphological characteristics, membrane attack complex (MAC), cell morphology, protein levels. Results ingredients found serum underscored their successful absorption rats. In rats, induced significant reduction proteinuria, MAC, C5b-9, glomerular basement thickness, along with drop apoptotic podocytes. Similarly, exerted protective effect against injury Furthermore, inhibition ERK/CK2-α/β-catenin pathway-mediated epithelial-to-mesenchymal transition (EMT) be involved anti-apoptotic podocytes, marked vimentin α-SMA induction Synaptopodin Podocin Conclusion Inhibition EMT via pathway may main which suppresses apoptosis

Язык: Английский

Процитировано

0