Alpha-klotho and peritoneal membrane status: A hypothesis generating study

Patrícia Branco, Ana Rita Martins, Rita Calça, Catarina Mateus, Maria João Jervis, Anabela Rodrigues, Sofia Azeredo Lopes, Ester Civantos, Sebastian Mas-Fontao, Augusta Gaspar, Sância Ramos, Judit Morello, Daniel Pinto Gomes, Sofia Azeredo Pereira

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1 Citation (Scopus)


Background: Long-term success of peritoneal dialysis relies on the integrity of the peritoneal membrane. This proof-of-concept study addressed the hypothesis that fibrosis is already present in the membrane at pre-dialysis and that the membrane status is related to the individual's uraemic fingerprint. Methods: A clinical-mechanistic, transversal, single-centre study was conducted. Pre-dialysis peritoneal biopsies were scored considering the submesothelial compact zone thickness (STM), vasculopathy and inflammation. We investigated if the membrane status could be inferred from a panel of proteins (α-Klotho, Galectin-3, FGF21, FGF23, Tweak, TNFα and hsPCR) in blood. Results: A total 58 incident patients aged 56 ± 15 years old were included, 31% female, 55% hypertension, 29% diabetic and 24% obese. Person-to-person STM was found to be highly variable and 38% of patients were fibrosis positive. Both α-Klotho (Spearman r = −.7491, p < 0.001) and FGF21 (Spearman r = −.5102, p < 0.001) were negatively associated with STM. α-Klotho, but not FGF21, was able to discriminate fibrosis from nonfibrosis with/without inflammation and vasculopathy. PLS models identified α-Klotho as the protein most relevant for fibrosis. α-Klotho was independently associated with fibrosis of the peritoneal membrane (OR =.991 (.896–.997), p = 0.002). Conclusion: Before the start of dialysis in incident patients, some patients already present fibrosis of the peritoneal membrane and other patients do not. Our findings suggest that α-Klotho may be implicated in fibrosis of the peritoneal membrane.

Original languageEnglish
Article numbere13903
JournalEuropean Journal Of Clinical Investigation
Issue number3
Early online date2022
Publication statusPublished - Mar 2023


  • biopsy
  • cytokines
  • diabetes
  • peritoneal membrane fibrosis
  • precision medicine
  • uraemic toxins


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