ArticleInternational journal of molecular sciences2023
Emerging Perspectives on the Rare Tubulopathy Dent Disease: Is Glomerular Damage a Direct Consequence of ClC-5 Dysfunction?
Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.
- Dent disease: clinical practice recommendations.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Guideline
- The kidney in genetic metabolic disorders.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2026Article
- Tubular proteinuria due to hereditary endocytic receptor disorder of the proximal tubule: Dent disease and chronic benign proteinuria.Pediatric nephrology (Berlin, Germany) · 2025Review
- Phenotype and genotype analyses of 21 Chinese patients with Dent disease.Journal of biomedical research · 2025Article
- Targeting ion channel networks in diabetic kidney disease: from molecular crosstalk to precision therapeutics and clinical innovation.Frontiers in medicine · 2025Review
- The Apical Endocytic-Lysosomal Apparatus in CLCN5 Mutations with Phenotypic-Genotypic Correlations in Three Cases.International journal of molecular sciences · 2024Article
- Characterization of pre-mRNA Splicing Defects Caused byBiomedicines · 2023Article
- New Trends in Pathology: From Cell Morphology to Molecular Medicine.International journal of molecular sciences · 2023Article
- Dent Disease 1 Presented Early with Bartter-Like Syndrome Features and Rickets: A Case Report.Case reports in nephrology and dialysisArticle
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Dent disease (DD1) is a rare tubulopathy caused by mutations in the CLCN5 gene. Glomerulosclerosis was recently reported in DD1 patients and ClC-5 protein was shown to be expressed in human podocytes. Nephrin and actin cytoskeleton play a key role for podocyte functions and podocyte endocytosis seems to be crucial for slit diaphragm regulation. The aim of this study was to analyze whether ClC-5 loss in podocytes might be a direct consequence of the glomerular damage in DD1 patients. Three DD1 kidney biopsies presenting focal global glomerulosclerosis and four control biopsies were analyzed by immunofluorescence (IF) for nephrin and podocalyxin, and by immunohistochemistry (IHC) for ClC-5. ClC-5 resulted as down-regulated in DD1 vs. control (CTRL) biopsies in both tubular and glomerular compartments (p < 0.01). A significant down-regulation of nephrin (p < 0.01) in DD1 vs. CTRL was demonstrated. CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats/Caspase9) gene editing of CLCN5 in conditionally immortalized human podocytes was used to obtain clones with the stop codon mutation p.(R34Efs*14). We showed that ClC-5 and nephrin expression, analyzed by quantitative Reverse Transcription/Polymerase Chain Reaction (qRT/PCR) and In-Cell Western (ICW), was significantly downregulated in mutant clones compared to the wild type ones. In addition, F-actin staining with fluorescent phalloidin revealed actin derangements. Our results indicate that ClC-5 loss might alter podocyte function either through cytoskeleton disorganization or through impairment of nephrin recycling.
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Registered trials
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