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dc.contributor.authorStefansson, Vidar Tor Nyborg
dc.contributor.authorNair, Viji
dc.contributor.authorMelsom, Toralf
dc.contributor.authorLooker, Helen C.
dc.contributor.authorMariani, Laura H.
dc.contributor.authorFermin, Damian
dc.contributor.authorEichinger, Felix
dc.contributor.authorMenon, Rajasree
dc.contributor.authorSubramanian, Lalita
dc.contributor.authorLadd, Patricia
dc.contributor.authorHarned, Roger
dc.contributor.authorHarder, Jennifer L.
dc.contributor.authorHodgin, Jeffrey B.
dc.contributor.authorBjornstad, Petter
dc.contributor.authorNelson, Peter J.
dc.contributor.authorEriksen, Bjørn Odvar
dc.contributor.authorNelson, Robert G.
dc.contributor.authorKretzler, Matthias
dc.date.accessioned2023-01-05T10:09:46Z
dc.date.available2023-01-05T10:09:46Z
dc.date.issued2022-08-31
dc.description.abstractHyperfiltration is a state of high glomerular filtration rate (GFR) observed in early diabetes that damages glomeruli, resulting in an iterative process of increasing filtration load on fewer and fewer remaining functional glomeruli. To delineate underlying cellular mechanisms of damage associated with hyperfiltration, transcriptional profiles of kidney biopsies from Pima Indians with type 2 diabetes with or without early-stage diabetic kidney disease were grouped into two hyperfiltration categories based on annual iothalamate GFR measurements. Twenty-six participants with a peak GFR measurement within two years of biopsy were categorized as the hyperfiltration group, and 26 in whom biopsy preceded peak GFR by over two years were considered pre-hyperfiltration. The hyperfiltration group had higher hemoglobin A1c, higher urine albumin-to-creatinine ratio, increased glomerular basement membrane width and lower podocyte density compared to the pre-hyperfiltration group. A glomerular 1240-gene transcriptional signature identified in the hyperfiltration group was enriched for endothelial stress response signaling genes, including endothelin-1, teckinase and transforming growth factor-b1 pathways, with the majority of the transcripts mapped to endothelial and inflammatory cell clusters in kidney single cell transcriptional data. Thus, our analysis reveals molecular pathomechanisms associated with hyperfiltration in early diabetic kidney disease involving putative ligand-receptor pairs with downstream intracellular targets linked to cellular crosstalk between endothelial and mesangial cells.en_US
dc.identifier.citationStefansson, Nair, Melsom, Looker, Mariani, Fermin, Eichinger, Menon, Subramanian, Ladd, Harned, Harder, Hodgin, Bjornstad, Nelson, Eriksen, Nelson, Kretzler. Molecular programs associated with glomerular hyperfiltration in early diabetic kidney disease. Kidney International. 2022;102(6):1345-1358en_US
dc.identifier.cristinIDFRIDAID 2079103
dc.identifier.doi10.1016/j.kint.2022.07.033
dc.identifier.issn0085-2538
dc.identifier.issn1523-1755
dc.identifier.urihttps://hdl.handle.net/10037/28038
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.relation.journalKidney International
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2022 The Author(s)en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.rightsAttribution 4.0 International (CC BY 4.0)en_US
dc.titleMolecular programs associated with glomerular hyperfiltration in early diabetic kidney diseaseen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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Attribution 4.0 International (CC BY 4.0)
Med mindre det står noe annet, er denne innførselens lisens beskrevet som Attribution 4.0 International (CC BY 4.0)