Authors
Chaoying Yan, Li Jian
Published in
Biomolecules & biomedicine. Oct 01, 2026. Epub Oct 01, 2026.
Abstract
Chronic kidney disease (CKD) is associated with progressive renal dysfunction, Klotho deficiency, and activation of profibrotic signaling. This study evaluated the functional and molecular effects of kidney-directed adeno-associated virus serotype 9 (AAV9)-mediated human Klotho delivery in experimental CKD. Forty-eight male mice were studied in six groups: sham, untreated 5/6 nephrectomy, empty vector, low- and high-dose AAV9-Klotho, and recombinant Klotho. Vector was administered via the renal vein at week 4. The primary endpoint was week-16 serum creatinine, analyzed using a baseline-adjusted mixed model for repeated measures. High-dose AAV9-Klotho was associated with lower serum creatinine than empty vector (adjusted difference, -20.6 µmol/L; 95% confidence interval, -33.3 to -7.9; p = 0.0018), with concordant changes in blood urea nitrogen, proteinuria, and urinary albumin-to-creatinine ratio. Human Klotho expression increased with vector dose, accompanied by recovery of endogenous mouse Klotho. Fibrosis-associated and inflammatory markers, transforming growth factor-β receptor I abundance, and phosphorylation of mothers against decapentaplegic homologs 2 and 3 (Smad2/3) were lower after treatment, whereas transforming growth factor-β1 (TGF-β1) abundance remained unchanged. These findings associate kidney-directed AAV9-Klotho delivery with improved renal-function measures and modulation of TGF-β1/Smad2/3 signaling in experimental CKD. Histological antifibrotic efficacy and direct receptor-level mechanisms remain unconfirmed.
PMID:
42829956
Bibliographic data and abstract were imported from PubMed on 05 Oct 2026.
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