Purpose: To extend existing information of the transcriptome on human diabetic kidneys.

Methods: RNA sequencing was performed in kidney tissues from patients with biopsy-proven diabetes nephropathy (N=19) and healthy living kidney donors as controls (N=20).

Results: Principal Component Analysis showed a clear separation between glomerular and tubulointerstitial transcriptomic profiles. When comparing patient tissue with control tissue, DN patients displayed 1,550 and 4,530 differentially expressed genes in glomeruli and tubulointerstitium (adjusted p <0.01), respectively, compared to the living donors. Next, Gene Ontology and KEGG pathway analyses identified a glomerular enrichment of genes involved in inflammation and extracellular matrix organization, as well as a tubulointerstitial enrichment of genes involved in immunity and apoptosis. Several specific gene modules associated with renal function were revealed using a weighted gene co-expression network analysis.

Conclusions: The results show consistency with previous microarray findings but more importantly, also provide information on new transcripts associated with DN within the two compartments making up the functional unit (the nephron) responsible for glomerular filtration and reabsorption in the kidneys. Prominent disease-specific changes occur in both glomeruli and tubulointerstitium including relevant cellular processes such as reorganization of extracellular matrix and inflammation (glomeruli) well as apoptosis (tubulointerstitium). The results emphasize the potential of utilizing high-throughput transcriptomics to decipher new disease pathways and treatment targets in this high-risk patient population.

Update 211106: Gene names have been corrected for the following genes

Number Gene name
2143 SEP15
7307 SEPT10
8566 MARS2
9417 SEPT2
13723 SEPT11
17104 SEPT8
21764 SEPT7
22089 SEPT14
25837 SEPT6
30717 DEC1
46263 SEPT12
46970 SEPT1
50732 SEPT4
51295 SEPT9
58023 SEPT5
58958 SEPT3

Download raw counts for glomerular compartment Raw_counts_glom

Download raw counts for tubulointerstitial compartment Raw_counts_tub

RNA-sequencing of kidney tissue from patients with biopsy-proven diabetes nephropathy