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Table 7 miRNA studies in chronic kidney disease

From: Genomic approaches in the search for molecular biomarkers in chronic kidney disease

PMID

Author

Year

Sample

Patients

Ethnics

Methodology

Main findings

27872161

Khurana

2017

Urine exosomes

15 CKD

Caucasian

Ion proton system for NGS

ncRNASeqScan

Sixteen miRNAs differentially expressed

 Increased: let-7c-5p, miR-222-3p, miR-27a-3p, miR-27b-3p, miR-296-5p, miR-31-5p, miR-3687, miR-6769b-5p, and miR-877-3p

 Decreased: miR-133a, miR-133b, miR-15a-5p, miR-181a-5p, miR-34a-5p, miR-181c-5p, and miR1-2

28077372

Muralidharan

2017

28 CKD

 

Affymetrix GeneChip miR 4.0

  
   

Urine

Blood (circulating)

   

Differential expression of 384 urinary and 266 circulatory miRNAs between CKD patients with eGFR≥30 vs.  < 30 ml/min/1.73 m2

Pathway analysis mapped multiple miRNAs to TGF-β signalling-related mRNA targets

Urine downregulation of let-7a and upregulation of miR-130a in patients with eGFR < 30 ml/min/1.73 m2

Both urine and plasma upregulation of miR-1825 and miR-1281 in patients with decreased eGFR

Plasma downregulation of miR-423 in patients with decreased eGFR

28771472

Nandakumar

2017

Blood

15 CKD

15 non CKD

African American

RNA sequencing (347 miRNAs)

Fourteen significant miRNAs:

 Upregulated: miR-29c-5p, miR-345-5p, miR-142-3p, miR-339-3p

 Downregulated: miR-17-5p, miR-130a-3p, miR-15b-5p, miR-106b-3p, miR-106a-5p, miR-16-5p, miR-181a-5p, miR-1285-3p, miR-15a-5p, miR-210-3p

The most significant miRNA was miR-17-5p (log2 fold change = − 0.77; p = 6.7∙10−4)

Downregulation of two other miRNAs in the miR-17 family (miR-106a-5p, miR-106b-3p)

Downregulation of three members of miR-15 family (miR-15a-5p, miR-15b-5p, and miR-16-5p)

27650800

Rivoli

2017

Blood (extra-cellular vesicles)

30 CKD

17 ESRD pre-HD

15 post-kidney transplantation 22 HC

 

qRT-PCR: miR-122 miR-885

Total circulating miRNA was lower in patients with CKD

miR-122 not differentially expressed in CKD

Downregulation of circulating miR-122 in pre-HD (19-fold lower compared with healthy controls

miR-122 not differentially expressed in patients with renal transplantation

Downregulation of miR-885 in ESRD patients (fourfold compared to healthy subjects) and upregulation by haemodialysis and renal trans-plantation

No correlation between eGFR and miR-122 in 30 patients with CKD

Circulating miR-122 was substantially reduced in ESRD patients pre-HD compared with the other groups (19.0-fold lower than healthy controls; 21.7-fold lower than CKD)

Downregulation of miR-885 in ESRD patients (fourfold compared to healthy subjects) and was increased by haemodialysis

Haemodialysis increased the concentration of miR-122

26267685

Zhang

2015

Serum

82 CKD-uremic, 16 HC

 

miR-155

Serum upregulation of miRNA-155 and IL-6 in all dialysis patients (p < 0.05)

miRNA-155 expression in peritoneal dialysis treated with alprostadil was down-regulated compared with peritoneal dialysis group or HD group (p < 0.05

Serum miRNA-155 was positively correlated with the level of IL-6 as well as CRP, while miR-155 was negatively correlated with HDL and albumin. Alprostadil could ameliorate the inflammatory conditions of uremic dialysis patients by inhibition of the IL-6 expression. Serum miRNA-155 may be a novel target for the treatment of uremic dialysis patients

25197634

Hu Yang-Yang

2014

Serum

60 Nephrolithiasis,  50 HC

Asian

qRT-PCR: miR-155

Overexpression of serum and urinary levels of miR-155 in nephrolithiasis patients

eGFR inversely correlated with urinary level of miR-155

24184689

Zawada

2014

PBMC

10 HD

10 HC

 

Massive analysis of cDNA ends

One-hundred and eighty-two miRNAs differentially expressed (p < 0.001) between HD patients and control subjects (75 upregulated in HD patients, 107 downregulated

Among the differentially expressed miRNAs, miR-21, miR- 26b, miR-146b, or miR-155 are involved in cardiovascular disease

23717629

Chen

2013

Blood (Circulating)

90 CKD

(Caucasians: African Americans: Others) 51:38:1

qRT-PCR: miR-125b miR-145 miR-155

Circulating levels correlated with progressive loss of eGFR by multivariate analyses. (For every one ml/min decrease in eGFR, there were a 0.05, 0.04, and 0.02 unit decreases in the expression of the miRNA for miR-125b, 145, and 155, respectively

10 CKD 3–4

10 HD

8 HC

 

Downregulation of circulating levels of miR-125b, miR-145 and miR-155 in CKD and hemodialysis patients compared to healthy volunteers

23946286

Lv

2013

Urine Exosomes

32 CKD

7 HC

Asian

qRT-PCR: miR-29a miR-29b miR-29c miR-200a miR-200b miR-200c

Downregulation of all 6 miRNAs in CKD

Downregulation of members of miR-29 and miR-200 families (p < 0.05) in urine, being able to distinguish CKD from controls

miR-29c correlated with both eGFR (r = 0.362; p < 0.05) and degree of tubulointerstitial fibrosis (r = -0.359; p < 0.05) for CKD patients

miR-29a and miR-29c could predict degree of tubulointerstitial fibrosis

22836280

Plé

2012

Platelets

10 CKD

5 HC

 

mRNA profiling

The levels of most miRNAs appeared to be corrected by dialysis, showing the regulatory role of platelet microRNAs in dialysis

Upregulation of miR-19b, a miRNA involved in platelet reactivity

miR-551b was found to be differentially expressed in the dialysis patients cohort, as compared to the healthy cohort

21891774

Neal

2011

Plasma (Circulating)

15 CKD-3

18 CKD-4

20 ESRD-HD

22 HC

 

Total level of small RNAs (18–25 nucleotides)

Downregulation of specific circulating miRNAs in patients with severe chronic renal failure, compared to patients with mild renal impairment or normal renal function

Correlation between circulating miRNAs and eGFR (p < 0.0001; r = 0.553)

       

Total small RNA concentration in plasma differentially expressed between normal/stage 3 and stage 4/ESRD (p < 0.0001; Mann–Whitney U-test)

      

qRT-PCR: miR-16 miR-21 miR-155 miR-210 miR-638

All five miRNAs expression inversely correlated with kidney function (eGFR)

Significant differences were observed between normal and Stage 4 CKD for miR-210, miR-16 and miR-155

Highly significant differences were observed between the normal/stage 3 CKD and ESRD cohorts (miR-638, miR-21, miR-155, miR-210, miR-16)

Significant differences were observed between Stage 4 CKD and ESRD patients for miR-210 and miR-16

The correlation between miRNA expression and eGFR remained significant when the patients undergoing haemodialysis are excluded from the analysis, with the exception of miR-21 and miR-155 levels

   

Urine

22 CKD

  

No association between urinary miRNA level and kidney function

Urine upregulation of miR-638 in stage 4 CKD compared to normal and stage 3 CKD patients (p < 0.006)

22045675

Starkey Lewis

2011

Serum

22 CKD

25 HC

Edinburgh

qRT-PCR: miR-122 miR-192

Overexpression of miR-122 and miR-192 in CKD patients

  1. CKD: chronic kidney disease; CRP: C-reactive protein; eGFR: estimated glomerular filtration rate; ESRD: end-stage renal disease; HC: healthy controls; HD: haemodyalisis; HDL: high-density lipoproteins; IL-6: interleukin 6; miRNA(s): microRNA(s); NGS: Next-generation sequencing; PBMC: peripheral blood mononuclear cells; qRT-PCR: quantitative real-time polymerase chain reaction; RNA: ribonucleic acid; TGF-β: transforming growth factor beta