Table 11.

Transcriptomics studies in kidney diseases

PMID	Author	Year	Sample	Patients	Ethnics	Methodology	Main findings
29642064	Zhou	2018	Gene expression microarray datasets retrieved from GEO repository	18 DKD/40 HC,  26 HTN/44 HC,  68 IgAN/44 HC,  36 MGN/44 HC,  35 FSGS/62 HC	–	Integrative bioinformatics analysis Affymetrix U133 Plus 2.0 Affymetrix U133 A	Glomeruli: 176 genes were differentially expressed among all diseases, 104 upregulated (e.g., FCN1, CX3CR1) and 72 downregulated (e.g., APOM, SLC13A1). Gene Ontology analysis showed mainly cellular components associated with diseased glomeruli, as integral components of the plasma membrane, extracellular space, and within the MHC class II protein complex. Pathway enrichment analysis showed dysregulation of several metabolic, immune response, and signalling pathways (e.g., lipids/lipoproteins and amino acids metabolism, SLC-mediated transmembrane transport, and IFN-γ pathway). Protein interaction network identified a cluster mainly associated with platelet dysfunction, abnormal interleukin signalling, and extracellular matrix organization Tubules: 50 genes were differentially expressed among all diseases, nine upregulated (e.g., COL3A1, MARCKS) and 41 downregulated (e.g., GDF15, RGS3). Gene Ontology analysis showed association mainly with molecule binding and transcription factor activity. Pathway enrichment analysis showed dysregulation of several signalling pathways (e.g., cholecystokinin receptor (CCKR), apoptosis, PI3 K-Akt, MAPK, and TGF-β signalling pathways). Protein interaction network identified a cluster mainly associated with SMAD2/SMAD3/SMAD4 heterotrimer-regulated transcription, TGF-β receptor complex signalling, and interleukin signalling Nine genes were significantly differentially expressed both in diseased glomeruli and tubules (IFI16, COL3A1, ZFP36, NR4A3, DUSP1, FOSB, HBB, FN1, PTPRC)
28158872	Zhao	2017	CD4 + T Cells	15 SLE 15 HC	United States	qRT-PCR	TNFAIP3 expression has been found downregulated in CD4 + T cells from SLE
26986150	Zhai	2016	B lymphocytes	166 IgAN 77 HC	China	qRT-PCR	Increased TNFSF13 expression is accompanied by upregulation of its receptors in B-lymphocytes from IgAN patients, inducing Gd-IgA1 overproduction
26631632	Ju	2015	Biopsy	55 CKD	United States	Microarray (Affymetrix GeneChip and TaqMan Low Density Arrays)	Urine levels of EGF correlated with tissue EGF transcript expression and predicted eGFR
26490557	Leal	2015	Peripheral Blood mononuclear cells	20 CKD 20 HD 11 HC	Brazil	qRT-PCR	NFE2L2 mRNA was positively correlated with NF-κB mRNA expression in CKD patients (r = 0.52, p = 0.02) and healthy individuals
26116588	Perlman	2015	Blood	20 T2DM + DKD,  20 HC	United States	qRT-PCR	transcripts levels differentially expressed in T2DM with nephropathy elevated expression occurred in early stage 1-2, before a significant decline in eGFR Interest in MCP-1, FGF-2, VEGF and EGF
23921255	Hara	2013	Leukocytes	40 CKD 20 HC	Japan	qRT-PCR	S100A12 expression was significantly higher in CKD patients compared to healthy controls
24347824	Yadav	2013	CD4+CD28null peripheral mononuclear cells	25 CKD 8 HC	India	qRT-PCR	Basal expression of IFN-γ, perforin, and granzyme B in CD4+CD28null cells was increased in CKD
23061738	Chen	2012	Urine	35 CKD 12 HC	China	qRT-PCR	CTGF and NOV genes were overexpressed in CKD
21906921	Spoto	2012	Plasma	75 CKD 33 HC	Italy	qRT-PCR	Upregulation of TNF-α was inversely correlated with eGFR Increase of plasma IL-6 in early stages of CKD, without showing any further increase at more severe stages
23024773	Rudnicki	2012	Biopsy	3 DKD 7 HTN 19 IgAN 10 MCD 7 FSGS 8 MGN 2 LN 2 MPGN 1 RPGN 16 Other	Switzerland	Microarray analysis	Correlation of versican isoforms V0 and V1 with creatinine levels
22969957	Tachaudomdach	2012	Biopsy	39 LN	Thailand	qRT-PCR	TGF-β1 and collagen I were correlated with CTGF expression Baseline eGFR and Renal CTGF mRNA expression were inversely correlated
20650904	Brabcova	2011	Biopsy	51 IgAN	Czech Republic	qRT-PCR	Higher TGF-β1 expression associated with IgAN progression
21640098	Chon	2011	Leukocytes	20 CKD 10 HC	Netherlands	qRT-PCR	Inverse correlation of leukocyte angiotensin II AT1 receptor mRNA expression with renal function Leukocyte angiotensin II AT1 receptor expression is higher in CKD
21040163	Lepenies	2010	Biopsy	64 CKD	UK	qRT-PCR	Inverse correlation of mRNA expression of peroxisome proliferator-activated receptor gamma (PPARγ) with renal function
19698090	Granata	2009	Peripheral blood mononuclear cells	9 CKD II-III, 17 HD,  8 HC	Helsinki	Microarray analysis	COX6C, COX7C, ATP5ME, and UQCRH were all significantly higher in CKD IV-V compared to CKD II-III and HC
18758661	Ibrahim	2008	Biopsy	20 T2DM,  4 normal tissue from renal tumor patients	Egyptian	qRT-PCR	Increased PKC alpha gene expression in diabetic patients with CKD PKC alpha gene concentrations and proteinuria had significant correlation in diabetic patients.
18784644	Zehnder	2008	Urine	174 CKD	81.6% white, 10.9% Asian, 6.9% Afro-Caribbean	qRT-PCR	MCP-1 expression was increased in those with acute renal inflammation
16564935	Szeto	2006	Urine	131 CKD	China	qRT-PCR	Urinary HGF expression remained an independent predictor of the primary end point, it was increased in those at risk of end point.
15561743	Szeto	2005	Urine	29 CKD 10 HC	China	qRT-PCR	Overexpression of TGF-β and MCP-1 was associated with glomerulosclerosis Overexpression of collagen IV was associated with CKD

Akt: Protein kinase B, also known as Akt; APOM: apolipoprotein M; AT1: angiotensin II Type 1 receptor; ATP5ME: ATP synthase membrane subunit e; CCKR: cholecystokinin receptor; CD4: cluster of differentiation 4; CD28: cluster of differentiation 28; CKD: chronic kidney disease; COL3A1: collagen type III alpha 1 chain; COX6C: cytochrome c oxidase subunit 6C; COX7C: cytochrome c oxidase subunit 7C; CTGF: connective tissue growth factor; CX3CR1: C-X3-C motif chemokine receptor 1; DKD: diabetic kidney disease; DUSP1: dual specificity phosphatase 1; EGF: epidermal growth factor; eGFR: estimated glomerular filtration rate; FCN1: ficolin 1; FGF: fibroblast growth factor; FN1: fibronectin 1; FOSB: FosB proto-oncogene; AP-1 transcription factor subunit; FSGS: focal segmental glomerulosclerosis; Gd-IgA1: galactose-deficient hinge region O-glycans; GDF15: growth differentiation factor 15; GEO: gene expression omnibus;, HBB: hemoglobin subunit beta; HC: healthy controls; HD: hemodialysis; HGF hepatocyte growth factor; HTN: hypertension; IFI16: interferon gamma inducible protein 16; IFN-γ: interferon gamma; IgAN: IgA nephropathy; IL-6: interleukin 6; LN: lupus nephritis; MAPK: Mitogen-activated protein kinases; MARCKS: myristoylated alanine rich protein kinase C substrate; MCD: minimal change disease; MHC: major histocompatibility complex; MCP-1: monocyte Chemoattractant Protein-1; MGN: membranous nephropathy; MPGN: membranoproliferative glomerulonephritis; mRNA: messenger ribonucleic acid; NF-κB: NF-kappa B complex subunits; NFE2L2: nuclear factor, erythroid 2 like 2; NOV: nephroblastoma overexpressed; NR4A3: nuclear receptor subfamily 4 group A member 3; PKC: protein kinase C; PPARγ: peroxisome proliferator-activated receptor gamma; PTPRC: protein tyrosine phosphatase, receptor type C; PI3K: phosphatidylinositol-3-kinases; qRT-PCR: quantitative reverse transcription polymerase chain reaction; RGS3: regulator of G protein signalling 3; RPGN: rapidly progressive glomerulonephritis; S100A12: S100 calcium binding protein A12; SLC: human solute carrier gene superfamily; SLC13A1: solute carrier family 13 member 1; SLE: systematic lupus erythematosus; SMAD2: SMAD family member 2; SMAD3: SMAD family member 3; SMAD4: SMAD family member 4; T1DM: type 1 diabetes mellitus; T2DM: type 2 diabetes mellitus; TNF: tumour necrosis factor superfamily; TGF-β1: transforming growth factor beta 1; TNF-α: tumour necrosis factor alpha; TNFAIP3: TNF alpha induced protein 3; TNFSF13: TNF superfamily member 13; TGF-β: transforming growth factor beta; UK: United Kingdom; UQCRH: ubiquinol-cytochrome c reductase hinge protein; VEGF: vascular endothelial growth factor; ZFP36: ZFP36 ring finger protein