PXD026709-2

PXD026709 is an original dataset announced via ProteomeXchange.

Title	Glomerular proteomic profiling of kidney biopsies with hypertensive nephropathy reveals a signature of disease progression
Description	Background and Objective: Hypertensive nephropathy (HN) requires a kidney biopsy as gold-standard for its diagnosis but histological findings are not entirely specific and lack specific prognostic markers. We aimed at defining prognostic candidate markers based on glomerular protein signatures. Method: We included adult patients (n=17) with an eGFR >30 ml/min/1.73m2 and proteinuria <3g/d from the Norwegian Kidney Biopsy Registry: stable patients (n=9) and subjects with HN progression (n=8) leading to end-stage renal disease (ESRD) within 20 years of follow-up. Glomerular cross-sections were microdissected from archival kidney biopsy sections and processed for protein extraction. Proteomic analyses were performed using Q-exactive HF mass spectrometer and relative glomerular protein abundance were compared between progressive vs non-progressive patients. Results: Amongst 1870 quality filtered proteins, we identified 58 proteins with an absolute fold change (FC)>1.5, p<0.05, including 17 proteins with absolute FC >2, indicative of HN progression (highest FC: Cadherin 16 and UDP-glucuronosyl-transferase 2B7). Hierarchical cluster and principal component analysis (PCA) with the 17 proteins showed clear separation of samples into HN progressors and non-progressors. Supervised classifier analysis (K nearest neighbour) identified a set of five proteins which classified 16/17 samples correctly. Applying Geneset Enrichment Analysis (GSEA), in general metabolic pathways were enriched in progressors, and structural cell pathways enriched in non-progressors. Pathway analysis identified Epithelial Adherens Junction Signaling as the most affected canonical pathway. The signature of HN progression is different from the respective signature of IgA progression. Conclusion: Glomerular proteomic profiling can be used to discriminate progressors from non-progressors in HN.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:48:14.473.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kenneth Finne
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-06-15 03:18:58	ID requested
1	2023-05-23 08:28:57	announced
⏵ 2	2023-11-14 08:48:15	announced	2023-11-14: Updated project metadata.

Mikkelsen H, Vikse BE, Eikrem O, Scherer A, Finne K, Osman T, Marti HP, Glomerular proteomic profiling of kidney biopsies with hypertensive nephropathy reveals a signature of disease progression. Hypertens Res, 46(1):144-156(2023) [pubmed]

submitter keyword: Human, Microdissection, Hypertensive nephropathy, Kidney, Glomerulus, Proteomics

Hans Peter Marti
contact affiliation	Renal Research Group, Department of Clinical Medicine, Faculty of Medicine, University of Bergen, Norway
contact email	Hans-Peter.Marti@uib.no
lab head
Kenneth Finne
contact affiliation	University of Bergen
contact email	kenneth.finne@uib.no
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD026709
     1. Label: PRIDE project
     2. Name: Glomerular proteomic profiling of kidney biopsies with hypertensive nephropathy reveals a signature of disease progression