• 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,... more GomesDaniel PintoDPPathology Department, Hospital Santa Cruz, Centro Hospitalar de Lisboa Ocidental (CLHO), Lisboa, Portugal., and Sofia Azeredo Pereira. less
• Nephrology Department, Hospital Santa Cruz, Centro Hospitalar de Lisboa Ocidental (CLHO), Lisboa, Portugal.
• Eur. J. Clin. Invest. 2023 Mar 1; 53 (3): e13903e13903.

BackgroundLong-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.MethodsA 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.ResultsA 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).ConclusionBefore 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.© 2022 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

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