Molecular programs associated with glomerular hyperfiltration in early diabetic kidney disease
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https://hdl.handle.net/10037/28038Dato
2022-08-31Type
Journal articleTidsskriftartikkel
Peer reviewed
Forfatter
Stefansson, Vidar Tor Nyborg; Nair, Viji; Melsom, Toralf; Looker, Helen C.; Mariani, Laura H.; Fermin, Damian; Eichinger, Felix; Menon, Rajasree; Subramanian, Lalita; Ladd, Patricia; Harned, Roger; Harder, Jennifer L.; Hodgin, Jeffrey B.; Bjornstad, Petter; Nelson, Peter J.; Eriksen, Bjørn Odvar; Nelson, Robert G.; Kretzler, MatthiasSammendrag
Hyperfiltration 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.
Forlag
ElsevierSitering
Stefansson, 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):1345-1358Metadata
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