Alpha-klotho and peritoneal membrane status : A hypothesis generating study
© 2022 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:53 |
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| Enthalten in: |
European journal of clinical investigation - 53(2023), 3 vom: 20. März, Seite e13903 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Branco, Patrícia [VerfasserIn] |
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| Links: |
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| Themen: |
Biopsy |
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| Anmerkungen: |
Date Completed 14.02.2023 Date Revised 14.02.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/eci.13903 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM348906935 |
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| 245 | 1 | 0 | |a Alpha-klotho and peritoneal membrane status |b A hypothesis generating study |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a biopsy | |
| 650 | 4 | |a cytokines | |
| 650 | 4 | |a diabetes | |
| 650 | 4 | |a peritoneal membrane fibrosis | |
| 650 | 4 | |a precision medicine | |
| 650 | 4 | |a uraemic toxins | |
| 700 | 1 | |a Martins, Ana Rita |e verfasserin |4 aut | |
| 700 | 1 | |a Calça, Rita |e verfasserin |4 aut | |
| 700 | 1 | |a Mateus, Catarina |e verfasserin |4 aut | |
| 700 | 1 | |a Jervis, Maria João |e verfasserin |4 aut | |
| 700 | 1 | |a Rodrigues, Anabela |e verfasserin |4 aut | |
| 700 | 1 | |a Lopes, Sofia Azeredo |e verfasserin |4 aut | |
| 700 | 1 | |a Civantos, Ester |e verfasserin |4 aut | |
| 700 | 1 | |a Mas-Fontao, Sebastian |e verfasserin |4 aut | |
| 700 | 1 | |a Gaspar, Augusta |e verfasserin |4 aut | |
| 700 | 1 | |a Ramos, Sância |e verfasserin |4 aut | |
| 700 | 1 | |a Morello, Judit |e verfasserin |4 aut | |
| 700 | 1 | |a Gomes, Daniel Pinto |e verfasserin |4 aut | |
| 700 | 1 | |a Pereira, Sofia Azeredo |e verfasserin |4 aut | |
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