Biomarkers in Primary Focal Segmental Glomerulosclerosis in Optimal Diagnostic-Therapeutic Strategy

Musiała, Aleksandra; Donizy, Piotr; Augustyniak−Bartosik, Hanna; Jakuszko, Katarzyna; Banasik, Mirosław; Kościelska‐Kasprzak, Katarzyna; Krajewska, Magdalena; Kamińska, Dorota

doi:10.3390/jcm11123292

Cited by 12 publications

(10 citation statements)

References 141 publications

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“…Circulating permeability factors are most likely to blame. Despite decades of research and several identified potential factors, no unifying concept for circulating factors has been established [ 73 ]. There is an unmet clinical need for early and specific biomarkers to detect FSGS and predict prognosis and treatment response.…”

Section: The Potential Use Of Raman Spectroscopy In Specific Kidney D...mentioning

confidence: 99%

The Potential Applications of Raman Spectroscopy in Kidney Diseases

Delrue

Speeckaert

2022

JPM

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Raman spectroscopy (RS) is a spectroscopic technique based on the inelastic interaction of incident electromagnetic radiation (from a laser beam) with a polarizable molecule, which, when scattered, carries information from molecular vibrational energy (the Raman effect). RS detects biochemical changes in biological samples at the molecular level, making it an effective analytical technique for disease diagnosis and prognosis. It outperforms conventional sample preservation techniques by requiring no chemical reagents, reducing analysis time even at low concentrations, and working in the presence of interfering agents or solvents. Because routinely utilized biomarkers for kidney disease have limitations, there is considerable interest in the potential use of RS. RS may identify and quantify urinary and blood biochemical components, with results comparable to reference methods in nephrology.

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Section: The Potential Use Of Raman Spectroscopy In Specific Kidney D...mentioning

confidence: 99%

The Potential Applications of Raman Spectroscopy in Kidney Diseases

Delrue

Speeckaert

2022

JPM

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“…Secondary FSGS occurs due to known stress, toxic, immunologic, or viral factors that damage podocytes, for example, hypertension, obesity, or several nephrotoxic medications. Primary FSGS is caused by an unidentified “circulating factor,” which negatively affects podocytes and thus increases the permeability of the glomerular filtration barrier ( 7 ). Genetic FSGS exhibits a high underlying genetic heterogeneity and is considered a rare monogenic disorder.…”

Section: Introductionmentioning

confidence: 99%

The most common founder pathogenic variant c.868G > A (p.Val290Met) in the NPHS2 gene in a representative adult Czech cohort with focal segmental glomerulosclerosis is associated with a milder disease and its underdiagnosis in childhood

Thomasová,

Zelinová,

Libik

et al. 2023

Front. Med.

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BackgroundGenetic focal segmental glomerulosclerosis (FSGS) is caused by pathogenic variants in a broad spectrum of genes that have a variable representation based on subjects' ethnicity and/or age. The most frequently mutated autosomal recessive gene in FSGS is NPHS2. In this study, we analyzed the spectrum of NPHS2 variants and their associated phenotype in Czech adult FSGS patients.MethodsA representative cohort of 234 adult patients with FSGS, derived from 225 families originating from all regions of Czechia, was analyzed by massively parallel sequencing. In this study, we focused on the comprehensive analysis of the NPHS2 gene. The histological classification of FSGS followed the Columbia classification.ResultsWe detected seven (3%) cases bearing homozygous or compound heterozygous pathogenic NPHS2 variants. A single pathogenic variant c.868G > A (p.Val290Met) was found in the majority of NPHS2-positive cases (86%; 6 out of 7) in histologically confirmed instances of FSGS. Its allele frequency among unrelated NPHS2-associated FSGS patients was 50% (6/12), and Haplotype analysis predicted its origin to be a result of a founder effect. There is an identical V290M-related haplotype on all V290M alleles spanning a 0,7 Mb region flanking NPHS2 in Central European FSGS populations. The phenotype of the p.Val290Met NPHS2-associated FSGS demonstrated a later onset and a much milder course of the disease compared to other NPHS2 pathogenic variants associated with FSGS. The mean age of the FSGS diagnosis based on kidney biopsy evaluation was 31.2 ± 7.46 years. In 50% of all cases, the initial disease manifestation of proteinuria occurred only in adulthood, with 83% of these cases not presenting with edemas. One-third (33%) of the studied subjects progressed to ESRD (2 out of 6) at the mean age of 35.0 ± 2.82 years.ConclusionsWe identified the most prevalent pathogenic variant, p.Val290Met, in the NPHS2 gene among Czech adult FSGS patients, which has arisen due to a founder effect in Central Europe. The documented milder course of the disease associated with this variant leads to the underdiagnosis in childhood. We established the histopathological features of the NPHS2-associated adult FSGS cases based on the Columbia classification. This might improve patient stratification and optimize their treatment.

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“…Primary FSGS is linked to circulating factors that affect podocyte structure 10 , 11 . The most important point of cell injury in primary FSGS is the podocyte since it is considered a podocytopathy 4 , 12 .…”

Section: Introductionmentioning

confidence: 99%

Evaluation of glomerular sirtuin-1 and claudin-1 in the pathophysiology of nondiabetic focal segmental glomerulosclerosis

Lopes-Gonçalves,

Costa-Pessoa,

Pimenta

et al. 2023

Sci Rep

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Focal segmental glomerulosclerosis (FSGS) is the leading cause of nephrotic syndrome, which is characterized by podocyte injury. Given that the pathophysiology of nondiabetic glomerulosclerosis is poorly understood and targeted therapies to prevent glomerular disease are lacking, we decided to investigate the tight junction protein claudin-1 and the histone deacetylase sirtuin-1 (SIRT1), which are known to be involved in podocyte injury. For this purpose, we first examined SIRT1, claudin-1 and podocin expression in kidney biopsies from patients diagnosed with nondiabetic FSGS and found that upregulation of glomerular claudin-1 accompanies a significant reduction in glomerular SIRT1 and podocin levels. From this, we investigated whether a small molecule activator of SIRT1, SRT1720, could delay the onset of FSGS in an animal model of adriamycin (ADR)-induced nephropathy; 14 days of treatment with SRT1720 attenuated glomerulosclerosis progression and albuminuria, prevented transcription factor Wilms tumor 1 (WT1) downregulation and increased glomerular claudin-1 in the ADR + SRT1720 group. Thus, we evaluated the effect of ADR and/or SRT1720 in cultured mouse podocytes. The results showed that ADR [1 µM] triggered an increase in claudin-1 expression after 30 min, and this effect was attenuated by pretreatment of podocytes with SRT1720 [5 µM]. ADR [1 µM] also led to changes in the localization of SIRT1 and claudin-1 in these cells, which could be associated with podocyte injury. Although the use of specific agonists such as SRT1720 presents some benefits in glomerular function, their underlying mechanisms still need to be further explored for therapeutic use. Taken together, our data indicate that SIRT1 and claudin-1 are relevant for the pathophysiology of nondiabetic FSGS.

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Biomarkers in Primary Focal Segmental Glomerulosclerosis in Optimal Diagnostic-Therapeutic Strategy

Cited by 12 publications

References 141 publications

The Potential Applications of Raman Spectroscopy in Kidney Diseases

The Potential Applications of Raman Spectroscopy in Kidney Diseases

The most common founder pathogenic variant c.868G > A (p.Val290Met) in the NPHS2 gene in a representative adult Czech cohort with focal segmental glomerulosclerosis is associated with a milder disease and its underdiagnosis in childhood

Evaluation of glomerular sirtuin-1 and claudin-1 in the pathophysiology of nondiabetic focal segmental glomerulosclerosis

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