Urinary Clusterin is a Biomarker of Renal Epithelial Senescence and Predicts Human Kidney Disease Progression
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View abstract on PubMed
Summary
This summary is machine-generated.Urinary clusterin-to-creatinine ratio (uCCR) is a novel noninvasive biomarker for senescent renal epithelia, predicting kidney disease progression and outcomes in patients with chronic kidney disease (CKD). This finding offers a new tool for clinical trials of senolytic therapies.
Area Of Science
- Nephrology
- Cellular Biology
- Biomarker Discovery
Background
- Cellular senescence, characterized by irreversible cell cycle arrest and altered secretion, is implicated in driving kidney fibrosis.
- Senescent renal epithelia are key contributors to kidney fibrosis, but a lack of noninvasive biomarkers hinders clinical trials for senolytic drugs.
Purpose Of The Study
- To identify and validate a noninvasive urinary biomarker for senescent renal epithelia in patients with chronic kidney disease (CKD).
- To assess the predictive value of the identified biomarker for adverse renal outcomes.
Main Methods
- Proteomic analysis, immunofluorescence staining, and spatial transcriptomics were used on urine and kidney biopsies from CKD patients.
- Quantitative PCR analyzed clusterin and senescence markers in irradiated human renal epithelia.
- ELISAs quantified urinary biomarker concentrations to predict end-stage kidney disease or significant renal function loss.
Main Results
- Urinary clusterin-to-creatinine ratio (uCCR) strongly correlated with senescent renal epithelia (P21+Ki67-) in both urine and biopsy cohorts.
- Clusterin was transcriptionally upregulated in senescent epithelia.
- Elevated uCCR predicted adverse renal outcomes in CKD patients, independent of established risk factors like eGFR and uACR.
Conclusions
- The urinary clusterin-to-creatinine ratio (uCCR) serves as a reliable noninvasive surrogate for quantifying senescent renal epithelia.
- uCCR is a valuable predictor of clinical outcomes in human kidney disease, offering a new avenue for patient monitoring and therapeutic development.
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