Clinical Research Directory

Effect of Cholecalciferol on Mucin-1 Levels in Urinary Extracelllular Vesicles in Individuals With Autosomal Dominant Tubulo-Interstitial Kidney Disease Due to MUC1 Mutations (ADTKD-MUC1)

Autosomal dominant tubulointerstitial kidney disease due to MUC1 mutations (ADTKD-MUC1) is caused by mutations in the MUC1 gene encoding the protein mucin-1. The most frequently reported mutation is a cytosine insertion causing a frameshift and resulting in the production of an abnormal protein (MUC1-fs). The primary characteristic of ADTKD-MUC1 is slowly progressive chronic kidney disease, with age-dependent progression to end-stage kidney disease (ESKD). Although mucin-1 is expressed in numerous epithelial tissues, including sebaceous glands, the respiratory tract, mammary glands, and gastrointestinal tract, ADTKD-MUC1 is not typically associated with clinical manifestations outside the kidney. The Pafos region of Cyprus is home to one of the largest reported cohorts of patients with ADTKD-MUC1 worldwide, with an estimated prevalence of the MUC1 cytosine insertion of approximately 1 in 580 individuals. The chromosomal region at 1q22 associated with the disease was initially identified by investigators in Cyprus, and the Cypriot cohort has subsequently been extensively characterized and followed longitudinally. ADTKD-MUC1 currently has no approved disease-specific treatment, and most affected individuals eventually develop ESKD requiring kidney replacement therapy, at an average age of approximately 50 years. Intracellular accumulation of MUC1-fs is considered a major contributor to the pathogenesis of ADTKD-MUC1. Researchers at the Broad Institute, Harvard Medical School, and Massachusetts Institute of Technology developed a high-content screening (HCS) platform using a cell-based immunofluorescence assay to evaluate the effects of approximately 4,500 compounds from the Broad Institute drug repurposing library on patient-derived primary cells. The library included compounds at various stages of preclinical and clinical development, including FDA-approved drugs and supplements. Cholecalciferol (vitamin D3) was identified as a compound capable of reducing both wild-type mucin-1 (MUC1) and frameshift mucin-1 (MUC1-fs) protein levels in vitro, as demonstrated by immunofluorescence experiments. Based on these preliminary findings, the investigators hypothesize that administration of a single high dose of cholecalciferol to patients with ADTKD-MUC1 may reproduce the reduction in MUC1-fs protein levels observed in vitro. Cholecalciferol (vitamin D3) is commonly used for the prevention and treatment of vitamin D deficiency. The study therefore aims to investigate the effects of cholecalciferol administration on MUC1 and MUC1-fs protein levels in urinary extracellular vesicles collected from Cypriot patients with genetically confirmed ADTKD-MUC1 carrying the MUC1 cytosine insertion mutation.

Model Development and Application Based on Renal Pathology Images

This single-center retrospective observational cohort study will utilize digital renal pathology images along with corresponding clinical and laboratory data from patients who underwent kidney biopsy at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, between January 1, 2019, and March 31, 2026. Deep learning and image analysis techniques will be employed to develop and validate models for the pathological diagnosis and classification of kidney diseases. The study will also assess model performance in evaluating disease activity and chronicity, as well as investigate the association between image-derived features and long-term renal outcomes. Diagnoses will be established by consensus among three senior renal pathologists, who will serve as the reference standard. A minimum of 8,000 eligible cases are planned for inclusion, which will be divided into training, validation, and independent test sets.