Specific populations of urinary extracellular vesicles and proteins differentiate type 1 primary hyperoxaluria patients without and with nephrocalcinosis or kidney stones.
Exosomes
Microvesicles
Oxalate
Renal calcification
Urinary proteins
Urinary stone disease
Urinary vesicles
Journal
Orphanet journal of rare diseases
ISSN: 1750-1172
Titre abrégé: Orphanet J Rare Dis
Pays: England
ID NLM: 101266602
Informations de publication
Date de publication:
11 11 2020
11 11 2020
Historique:
received:
24
06
2020
accepted:
03
11
2020
entrez:
12
11
2020
pubmed:
13
11
2020
medline:
22
6
2021
Statut:
epublish
Résumé
Primary hyperoxaluria type 1 (PH1) is associated with nephrocalcinosis (NC) and calcium oxalate (CaOx) kidney stones (KS). Populations of urinary extracellular vesicles (EVs) can reflect kidney pathology. The aim of this study was to determine whether urinary EVs carrying specific biomarkers and proteins differ among PH1 patients with NC, KS or with neither disease process. Mayo Clinic Rare Kidney Stone Consortium bio-banked cell-free urine from male and female PH1 patients without (n = 10) and with NC (n = 6) or KS (n = 9) and an eGFR > 40 mL/min/1.73 m Total EVs and EVs from different types of glomerular and renal tubular cells (11/13 markers) were significantly (Q < 0.20) altered among PH1 patients without NC and KS, patients with NC or patients with KS alone. Three cellular adhesion/inflammatory (ICAM-1, MCP-1, and tissue factor) markers carrying EVs were statistically (Q < 0.20) different between PH1 patients groups. Three renal injury (β2-microglobulin, laminin α5, and NGAL) marker-positive urinary EVs out of 5 marker assayed were statistically (Q < 0.20) different among PH1 patients without and with NC or KS. The number of immune/inflammatory cell-derived (8 different cell markers positive) EVs were statistically (Q < 0.20) different between PH1 patients groups. EV generation markers (ANO4 and HIP1) and renal calcium/phosphate regulation or calcifying matrixvesicles markers (klotho, PiT1/2) were also statistically (Q < 0.20) different between PH1 patients groups. Only 13 (CD14, CD40, CFVII, CRP, E-cadherin, EGFR, endoglin, fetuin A, MCP-1, neprilysin, OPN, OPGN, and PDGFRβ) out of 40 proteins were significantly (Q < 0.20) different between PH1 patients without and with NC or KS. These results imply activation of distinct renal tubular and interstitial cell populations and processes associated with KS and NC, and suggest specific populations of urinary EVs and proteins are potential biomarkers to assess the pathogenic mechanisms between KS versus NC among PH1 patients.
Sections du résumé
BACKGROUND
Primary hyperoxaluria type 1 (PH1) is associated with nephrocalcinosis (NC) and calcium oxalate (CaOx) kidney stones (KS). Populations of urinary extracellular vesicles (EVs) can reflect kidney pathology. The aim of this study was to determine whether urinary EVs carrying specific biomarkers and proteins differ among PH1 patients with NC, KS or with neither disease process.
METHODS
Mayo Clinic Rare Kidney Stone Consortium bio-banked cell-free urine from male and female PH1 patients without (n = 10) and with NC (n = 6) or KS (n = 9) and an eGFR > 40 mL/min/1.73 m
RESULTS
Total EVs and EVs from different types of glomerular and renal tubular cells (11/13 markers) were significantly (Q < 0.20) altered among PH1 patients without NC and KS, patients with NC or patients with KS alone. Three cellular adhesion/inflammatory (ICAM-1, MCP-1, and tissue factor) markers carrying EVs were statistically (Q < 0.20) different between PH1 patients groups. Three renal injury (β2-microglobulin, laminin α5, and NGAL) marker-positive urinary EVs out of 5 marker assayed were statistically (Q < 0.20) different among PH1 patients without and with NC or KS. The number of immune/inflammatory cell-derived (8 different cell markers positive) EVs were statistically (Q < 0.20) different between PH1 patients groups. EV generation markers (ANO4 and HIP1) and renal calcium/phosphate regulation or calcifying matrixvesicles markers (klotho, PiT1/2) were also statistically (Q < 0.20) different between PH1 patients groups. Only 13 (CD14, CD40, CFVII, CRP, E-cadherin, EGFR, endoglin, fetuin A, MCP-1, neprilysin, OPN, OPGN, and PDGFRβ) out of 40 proteins were significantly (Q < 0.20) different between PH1 patients without and with NC or KS.
CONCLUSIONS
These results imply activation of distinct renal tubular and interstitial cell populations and processes associated with KS and NC, and suggest specific populations of urinary EVs and proteins are potential biomarkers to assess the pathogenic mechanisms between KS versus NC among PH1 patients.
Identifiants
pubmed: 33176829
doi: 10.1186/s13023-020-01607-1
pii: 10.1186/s13023-020-01607-1
pmc: PMC7659070
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
319Subventions
Organisme : NIH HHS
ID : U54DK083908
Pays : United States
Organisme : NIH HHS
ID : U54 DK100227
Pays : United States
Organisme : NIH HHS
ID : R25-DK101405
Pays : United States
Commentaires et corrections
Type : ErratumIn
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