The role of cyclooxygenase-2 (COX-2) and inflammatory markers in the progress of Alport syndrome in Egyptian children

BMC Pediatrics, Год журнала: 2025, Номер 25(1)

Опубликована: Янв. 24, 2025

Abstract Background Chronic inflammation and its control are crucial to the responses of glomerular renal tubular cells. This contributes pathogenic mechanisms advancement disease in Alport syndrome. The study aimed elucidate role cyclooxygenase-2, Interleukin 4, Plasminogen activating inhibitor 1, Prostaglandin E2 development course Methods In our inflammatory markers were evaluated 26 syndrome patients, 15 males 11 females 24 controls. Results Their age ranged from 4 16 years (mean ± SD was 8.50 2.877) normal controls matching sex. serum levels E2, 1 all patients. level increased significantly patients compared (588.68 73.08, 42.57 4.18, 42.32 3.49, 846.47 45.433, respectively versus (369.12 50.28, 25.52 4.98, 28.89 3.19, 312.79 40.53 respectively). Conclusion that causally connected have a delineated. may highlight speculate an innovative strategy for targeting creation safe efficient anti-inflammatory treatments inhibit progression

Язык: Английский

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Urinary Dickkopf-related protein 3 as a novel biomarker for kidney function decline in children with Alport syndrome

Pediatric Nephrology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 4, 2025

Abstract Background Chronic kidney disease (CKD) seriously affects the well-being and shortens life expectancy of children adolescents, but its progression is challenging to predict. Therefore, there an urgent need for biomarkers that can identify at risk faster CKD progression. Alport syndrome (AS) most common monogenetic glomerular disease. Urinary Dickkopf-related protein 3 ( DKK3) associated with a decline in estimated filtration rate (eGFR) adults advanced CKD. However, potential early detection prognostic value AS remain unknown. Methods Urine samples from 49 enrolled EARLY PRO-TECT trial were analyzed evaluate whether DKK3 could be Results levels patients higher than those healthy individuals reported literature. more elevated later stages AS. Furthermore, who not treated renin angiotensin system inhibitors (RASi) had children. Children above-average likely have increased albuminuria after 2 years follow-up below-average levels. Conclusion significantly There was association between levels, worsening albuminuria, function. These findings suggest may marker predicting damage Graphical

Язык: Английский

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A 15-year experience highlighting the spectrum of Alport kidney disease in the pediatric population and novel genetic variants in COL4A3–5

Pediatric Nephrology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 5, 2025

Abstract Background Alport kidney disease (AKD) presents one of the most prevalent genetic disorders, characterized by a complex background and diverse clinical manifestations. This study aimed to review features pediatric patients with COL4A3–5 variants identify novel variants. Methods Data were collected retrospectively at national level from up 19 years old, who underwent testing between 2008 2023. Patients pathogenic likely included. Their clinical, laboratory, characteristics presented. Results Over 15 years, 85 children adolescents tested positive for or Increasing incidence was noted as became more prevalent. One patient (1.2%) progressed failure six (7%) had extrarenal involvement. Pathogenic in COL4A3 , COL4A4 COL4A5 genes found 14 (16.4%), 34 (40.0%), 37 (43.6%) patients, respectively. diagnosed autosomal, X-linked, digenic AKD 55.2%, 43.6%, 1.2%, Eight recorded, their associated phenotype Conclusions expands AKD, presenting on spectrum mild hematuria progressive chronic disease. Genetic confirmation risk stratification population are critical ensure timely care potentially slow down progression Graphical abstract

Язык: Английский

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GLP-1 receptor agonists—another promising therapy for Alport syndrome?

Journal of Rare Diseases, Год журнала: 2025, Номер 4(1)

Опубликована: Фев. 28, 2025

Abstract Alport syndrome (AS) is a progressive monogenic glomerular kidney disease characterised by function decline, hearing loss, and ocular abnormalities, often leading to early-onset failure (KF). While current therapies, such as renin-angiotensin system inhibitors (RASi), offer some benefits, many patients still experience KF at young age, highlighting the need for additional treatment options. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged promising agents with demonstrated cardiovascular nephroprotective effects in type 2 diabetes (T2D) chronic (CKD) patients. Evidence from several major clinical trials has shown that GLP-1 RAs can reduce events slow CKD progression reducing albuminuria. Their potential mechanisms of action include anti-inflammatory, anti-fibrotic, antioxidative effects, making them particularly relevant AS, where inflammation fibrosis play crucial roles progression. This review explores therapeutic summarising pre-clinical data elucidating pathways through which might renoprotective benefits. We advocate further research into their application AS recommend inclusion future better understand impact on patient outcomes.

Язык: Английский

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Pathogenic variants in the Alport genes are prevalent in the Singapore multiethnic population with highest frequency in the Chinese

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

Опубликована: Март 5, 2025

Alport syndrome is a common monogenic kidney disease resulting from pathogenic variants in COL4A3, COL4A4 or COL4A5 genes. The estimated global population prevalence one 106 individuals for autosomal dominant (AD) and 2,320 sex-linked (XL) conditions. Here, we aimed to estimate the of carrying that cause Singapore, stratify by ancestry. We used population-scale genomic data 9,051 unrelated subjects, comprising 5,443 (60.8%) Chinese, 1,922 (21.4%) Indian 1,686 (17.8%) Malay individuals. with AD XL are 1 165 2,262 respectively. Additionally, 0.8% Chinese 0.3% populations carry variants, being 2.7 times more affected than Malays (95% CI:1.147-6.437, P = 0.027). Interestingly, each variant was associated people single two most prevalent COL4A3: c.3856G > A (p.Gly1286Arg) (n 8) c.4793T G (p.Leu1598Arg) 4), were exclusively found population. In conclusion, may be higher frequencies among Chinese. Furthermore, founder effects exist within ancestries.

Язык: Английский

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Identification of novel COL4A5 variants and prenatal diagnosis in three large families

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

Опубликована: Март 8, 2025

Alport syndrome (AS) is the second-most frequent monogenic kidney disease and 85% of cases are caused by mutations in genes α5 chains collagen type IV (COL4A5). The early diagnosis treatment essential for prognosis AS. clinical phenotypes AS very variable, which challenging to diagnose. Genetic sensitive accurate, can recognize affected individuals with mild phenotype predict age at renal failure treatment. In addition, genetic testing will offer available reproductive options, including prenatal preimplantation (PGT). this study, three novel COL4A5 variants (c.1834G > T, c.865G A c.1032 + 5G A) were found. These co-segregated multiple family members. vitro splicing assay indicated that variant resulted aberrant involving exon 18 skipping. healthy babies without these born PGT or diagnosis, respectively. Three gene provide insights into further counseling genotype–phenotype correlations.

Язык: Английский

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Collagen IV of basement membranes: I. Origin and diversification of COL4 genes enabling metazoan multicellularity, evolution and adaptation

Journal of Biological Chemistry, Год журнала: 2025, Номер unknown, С. 108496 - 108496

Опубликована: Апрель 1, 2025

Язык: Английский

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Type IV collagen-related nephropathy as a diagnosis in nephrotic syndrome

Pediatric Nephrology, Год журнала: 2024, Номер unknown

Опубликована: Окт. 8, 2024

Язык: Английский

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A vérvizelés okai gyermekkorban – a korszerű diagnosztika a kivizsgálás tükrében

Orvosi Hetilap, Год журнала: 2024, Номер 165(28), С. 1067 - 1078

Опубликована: Июль 14, 2024

A vérvizelés hátterében a betegségek széles spektruma állhat gyermekkorban, az egyszerű és gyorsan gyógyuló húgyúti fertőzésektől progrediáló súlyos glomerulonephritisig, mely vesefunkció gyors romlásához vezet. kivizsgálása során ezért elsődleges célunk orvosi szempontból jelentős esetek elkülönítése. vérvizeléshez társuló fehérjevizelés, magas vérnyomás vagy beszűkült progresszív vesebetegségre hívja fel figyelmet. Amennyiben makroszkópos, egyéb klinikai tünetek jellegzetesek, differenciáldiagnózis gyakran könnyű egyértelmű. Komplikáltabb esetekben azonban további noninvazív vizsgálómódszerek lehetnek szükségesek, mint ultrahangvizsgálat, vörösvértestek morfológiai vizsgálata, kalciumürítés, vizeletkémiai paraméterek, illetve fehérjevizelés mértékének meghatározása. családi anamnézis részletes felvétele örökletes okainak elkülönítésében segít. Tünetmentes esetén központokként változhat vesebiopszia elvégzésének indikációja. glomerularis felismerésének arányát jelentősen befolyásolja, hogy kritériumok teljesülése végzünk vesebiopsziát. Összefoglaló közleményünkben diagnosztikájának kihívásait mutatjuk be. Részletezzük definícióját, postglomerularis elkülönítésének lépéseit, áttekintjük hátterükben álló leggyakoribb betegségeket, melyek gyakoriságuk, lefolyásuk rossz prognózisuk miatt kihívást jelentenek mindennapi gyermeknefrológiai gyakorlatunk során. Orv Hetil. 2024; 165(28): 1067–1078.

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A Novel Loss-of-Function Variant in COL4A3 in a Consanguineous Moroccan Family Displaying the Alport Syndrome with Variable Clinical Expression

Molecular Syndromology, Год журнала: 2024, Номер unknown, С. 1 - 6

Опубликована: Июль 24, 2024

Alport syndrome (AS) is a rare genetic disorder characterized by abnormalities in the kidneys, ears, and eyes. Its clinical presentation typically manifests childhood or adolescence varies widely among affected individuals, ranging from isolated hematuria to end-stage renal disease. The causes of AS primarily involve mutations genes encoding type IV collagen COL4A3, COL4A4, COL4A5, which play essential roles maintaining structural integrity glomerular basement membrane kidney, cochlea, retina. They can be transmitted autosomal dominant, recessive, X-linked recessive. Here we report Moroccan consanguineous family with an 18-year-old girl who presented advanced failure microscopic hematuria. Her audiometry revealed hearing impairment. Urinalysis performed all asymptomatic members showed mother younger sister, while computed tomography excluded urologic cause. Using next-generation sequencing analysis, identified proband nonsense homozygous variant COL4A3 gene (c.4114C>T, p.Gln1372Ter) that was never reported literature, considered pathogenic according ACMG classification. Segregation analysis parents were heterozygous like elder brother, whereas sister mutated homozygous, other brother normal. We novel expends allelic spectrum AS. Clinical exploration testing intrafamilial variability, suggesting pseudo-dominant inheritance reduced penetrance.

Язык: Английский

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