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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
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   
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
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