Kidney transcriptomics signature of prospective rapid diabetic kidney disease progression
medrxiv(2024)
摘要
Previous cross-sectional transcriptomic studies on diabetic kidney disease (DKD) kidney tissue have shown correlations between gene expression and both disease status and kidney function at time of biopsy, but longitudinal data is scarce. 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 DKD patients. Patients were stratified into "rapid progressors" and "non-rapid progressors" based on clinical parameters (eGFR slope, CKD stage advancement, degree of albuminuria, composite 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. We identified 265 genes in glomeruli and tubulointerstitium that were significantly modulated in rapid vs non-rapid DKD progression. Rapid progression-associated genes showed enrichment for well-established (extracellular matrix organization, inflammation) as well as novel pathways in the context of DKD (circadian rhythm, cytoskeleton reorganization, NOTCH signaling). 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.
### Competing Interest Statement
DA, PJG, and AR are AstraZeneca employees. DA is an industrial PhD student at AstraZeneca. All other authors declare no competing interests.
### Funding Statement
This research was supported by grants provided by the Stockholm County Council (ALF Project), and the European Union Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 860977 titled TrainCKDis.
### Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
Written informed consent was obtained from all patients at study enrollment, and the study was approved by Swedish Ethical Review Authorities at both sites (Gothenburg and Stockholm) in accordance with the Declaration of Helsinki 1975, as revised in 2013.
I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.
Yes
I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
Yes
I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.
Yes
The raw RNA-seq data analyzed in this study is openly available at http://karokidney.org/rna-seq-dn/.
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