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<p>Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease, characterized by progressive cyst growth and decline in renal function. Data on urinary biomarkers in ADPKD patients receiving disease-modifying therapy remain limited. We conducted a single-center cross-sectional study in 80 adult ADPKD patients treated with tolvaptan to evaluate the association between urinary biomarkers of tubular protein handling and inflammation and markers of disease severity and progression. Urinary β2-microglobulin (BMG), monocyte chemotactic protein-1 (MCP-1), kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) were assessed alongside renal function parameters, including estimated glomerular filtration rate (eGFR). Disease progression was evaluated using annual eGFR slope, imaging-based disease severity according to the Mayo Imaging Classification, and height-adjusted total kidney volume (htTKV). Urinary BMG, particularly when indexed to creatinine, was significantly associated with both faster eGFR decline and greater structural disease severity. In contrast, inflammatory and tubular injury biomarkers (MCP-1, NGAL, and KIM-1) showed limited prognostic utility. Although MCP-1 and NGAL demonstrated modest univariate associations with eGFR decline, these associations did not persist after multivariable adjustment, and KIM-1 was not associated with functional or structural outcomes. In this tolvaptan-treated ADPKD cohort, urinary markers of proximal tubular protein handling, rather than inflammatory or injury-related biomarkers, were most strongly associated with disease severity and progression, suggesting that β2-microglobulin may capture residual tubular dysfunction under disease-modifying therapy.</p>

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Urinary biomarkers of tubular injury and inflammation in ADPKD patients under tolvaptan therapy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月28日

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  • Bogdan D. Agavriloaei,
  • Gianina Dodi,
  • Luminita E. Voroneanu,
  • Mugurel C. Apetrii,
  • Irina L. Mititiuc,
  • Adrian C. Covic

摘要

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease, characterized by progressive cyst growth and decline in renal function. Data on urinary biomarkers in ADPKD patients receiving disease-modifying therapy remain limited. We conducted a single-center cross-sectional study in 80 adult ADPKD patients treated with tolvaptan to evaluate the association between urinary biomarkers of tubular protein handling and inflammation and markers of disease severity and progression. Urinary β2-microglobulin (BMG), monocyte chemotactic protein-1 (MCP-1), kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) were assessed alongside renal function parameters, including estimated glomerular filtration rate (eGFR). Disease progression was evaluated using annual eGFR slope, imaging-based disease severity according to the Mayo Imaging Classification, and height-adjusted total kidney volume (htTKV). Urinary BMG, particularly when indexed to creatinine, was significantly associated with both faster eGFR decline and greater structural disease severity. In contrast, inflammatory and tubular injury biomarkers (MCP-1, NGAL, and KIM-1) showed limited prognostic utility. Although MCP-1 and NGAL demonstrated modest univariate associations with eGFR decline, these associations did not persist after multivariable adjustment, and KIM-1 was not associated with functional or structural outcomes. In this tolvaptan-treated ADPKD cohort, urinary markers of proximal tubular protein handling, rather than inflammatory or injury-related biomarkers, were most strongly associated with disease severity and progression, suggesting that β2-microglobulin may capture residual tubular dysfunction under disease-modifying therapy.