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Kidney transcriptomics signature of prospective rapid diabetic kidney disease progression

Acoba, Dianne LU orcid ; Levin, Anna ; Witasp, Anna ; Ebefors, Kerstin ; Mölne, Johan ; Greasley, Peter J ; Nyström, Jenny ; Wernerson, Annika and Reznichenko, Anna (2025) In BMC Nephrology 26. p.1-14
Abstract
Background
Previous cross-sectional transcriptomics studies on diabetic kidney disease (DKD) kidney tissue have shown correlations between gene expression and both disease status and kidney function at the time of biopsy; however, longitudinal data are scarce.

Methods
We utilized clinical follow-up data up to five years post-biopsy, linking the transcriptomes of diagnostic kidney biopsies to progression rates and outcomes in 19 patients with DKD. Patients were stratified into “rapid progressors” and “non-rapid progressors” based on clinical parameters (eGFR slope, CKD stage advancement, degree of albuminuria, composite outcome of kidney failure or 40% eGFR decline). Differential expression and pathway enrichment analyses... (More)
Background
Previous cross-sectional transcriptomics studies on diabetic kidney disease (DKD) kidney tissue have shown correlations between gene expression and both disease status and kidney function at the time of biopsy; however, longitudinal data are scarce.

Methods
We utilized clinical follow-up data up to five years post-biopsy, linking the transcriptomes of diagnostic kidney biopsies to progression rates and outcomes in 19 patients with DKD. Patients were stratified into “rapid progressors” and “non-rapid progressors” based on clinical parameters (eGFR slope, CKD stage advancement, degree of albuminuria, composite outcome of kidney failure or 40% eGFR decline). Differential expression and pathway enrichment analyses were performed to identify dysregulated genes and pathways associated with rapid progression.

Results
We identified 265 genes in the glomeruli and tubulointerstitium that were significantly modulated between rapid and non-rapid DKD progression. Rapid progression-associated genes were enriched for well-established (extracellular matrix organization, inflammation) and novel pathways in the context of DKD (circadian rhythm, cytoskeleton reorganization, NOTCH signaling).

Conclusions
This study illuminates kidney gene expression patterns that may be predictive of rapid progression in DKD and are distinct from those associated with cross-sectional kidney function. (Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
in
BMC Nephrology
volume
26
article number
504
pages
1 - 14
publisher
BioMed Central (BMC)
external identifiers
  • pmid:40887581
ISSN
1471-2369
DOI
10.1186/s12882-025-04364-0
language
English
LU publication?
no
id
5617f967-710c-4a3a-a156-eff3efeb2f32
date added to LUP
2025-09-02 09:58:59
date last changed
2025-09-02 10:39:53
@article{5617f967-710c-4a3a-a156-eff3efeb2f32,
  abstract     = {{Background<br/>Previous cross-sectional transcriptomics studies on diabetic kidney disease (DKD) kidney tissue have shown correlations between gene expression and both disease status and kidney function at the time of biopsy; however, longitudinal data are scarce.<br/><br/>Methods<br/>We utilized clinical follow-up data up to five years post-biopsy, linking the transcriptomes of diagnostic kidney biopsies to progression rates and outcomes in 19 patients with DKD. Patients were stratified into “rapid progressors” and “non-rapid progressors” based on clinical parameters (eGFR slope, CKD stage advancement, degree of albuminuria, composite outcome of kidney failure or 40% eGFR decline). Differential expression and pathway enrichment analyses were performed to identify dysregulated genes and pathways associated with rapid progression.<br/><br/>Results<br/>We identified 265 genes in the glomeruli and tubulointerstitium that were significantly modulated between rapid and non-rapid DKD progression. Rapid progression-associated genes were enriched for well-established (extracellular matrix organization, inflammation) and novel pathways in the context of DKD (circadian rhythm, cytoskeleton reorganization, NOTCH signaling).<br/><br/>Conclusions<br/>This study illuminates kidney gene expression patterns that may be predictive of rapid progression in DKD and are distinct from those associated with cross-sectional kidney function.}},
  author       = {{Acoba, Dianne and Levin, Anna and Witasp, Anna and Ebefors, Kerstin and Mölne, Johan and Greasley, Peter J and Nyström, Jenny and Wernerson, Annika and Reznichenko, Anna}},
  issn         = {{1471-2369}},
  language     = {{eng}},
  month        = {{08}},
  pages        = {{1--14}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{BMC Nephrology}},
  title        = {{Kidney transcriptomics signature of prospective rapid diabetic kidney disease progression}},
  url          = {{http://dx.doi.org/10.1186/s12882-025-04364-0}},
  doi          = {{10.1186/s12882-025-04364-0}},
  volume       = {{26}},
  year         = {{2025}},
}