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Table 9 miRNA studies in primary glomerulonephritis

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

PMID Author Year Sample Patients Ethnics Methodology Main findings
27000966 Duan 2016 Urine Discovery cohort: 9 IgAN,
3 HC
  Microarray
Agilent human miRNA V19.0 chips (1888 human miRNA)
Differential expression of 214 miRNAs in the IgAN group (112 miRNAs with p < 0.01)
Overexpression of miR-25-3p, miR-144-3p and miR-486-5p in IgAN (n = 93) compared to normal group (n = 82) or disease control (n = 40)
miR-25-3p, miR-144-3p and miR-486-5p from urinary sediment were demonstrated to be mainly derived from urinary erythrocytes
Overexpression of urinary supernatant microvesicles of miR-144-3p and miR-486-5p in the IgAN group
Confirmation cohort: 30 IgAN, 20 HC qRT-PCR: miR-25-3p miR-144-3p miR-486-5p miR-135a-3p miR-150-3p miR-638 Validation of four miRNAs (miR-25-3p, miR-144-3p-3p, miR-486-5p and miR-135a-3p) with p < 0.001
Validation cohort: 63 IgAN, 62 HC qRT-PCR: miR-25-3p miR-144-3p-3p miR-486-5p miR-135a-3p Overexpression of miR-25-3p (p < 0.001), miR-144-3p (p = 0.040) and miR-486-5p (p < 0.001) in the IgAN group
miR-135a-3p (p = 0.587) not differentially expressed
Urinary sediment overexpression of miR-25-3p (p < 0.001), miR-144-3p (p = 0.046) and miR-486-5p (p = 0.010) in the IgAN group compared with disease control group
The three urinary sediment miRNAs (miR-25-3p, miR-144-3p and miR-486-5p) showed good specificity and sensitivity for the diagnosis of IgAN (AUC value of 0.940 for the diagnosis of IgAN)
Positive correlation of miR-144-3p level with the change in eGFR (r = 0.286; p = 0.020) and negatively correlated with the change in 24-h urine protein (r = -0.259; p = 0.019)
Positive correlation of miR-25-3p level with the change in eGFR (r = 0.257; p = 0.038)
Overexpression of miR-25-3p was associated with renal function improvement
None of urinary sediment miRNA levels differed significantly between the groups with and without complete remission
26707063 Rudnicki 2016 Renal biopsy sections Discovery cohort: 12 progressive, 31 stable   qPCR (miRNA) and microarrays (mRNA) Downregulation of miR-30d, miR-140-3p, miR-532-3p, miR-194, miR-190, miR-204 and miR-206 in progressive cases
Progressive cases also showed a downregulation of miR-532-3p
Validation cohort: 8 progressive, 21 stable Downregulation of miR-206 and miR-532-3p was confirmed
25682967 Ramezani 2015 Urine exosomes 16 FSGS
5 MCD
5 HC
  GeneChip miRNA 3.0 Array qRT-PCR analysis Downregulation of urinary levels of mir-1915 and miR-663 in patients with FSGS compared to MCD and controls (p < 0.001)
Upregulation of urinary levels of miR-155 in patients with FSGS compared to patients with MCD and controls (p < 0.005)
Inverse correlation of urinary levels of miR-663 with eGFR (r = -0.50; p = 0.04) in patients with FSGS
Inverse correlation of urinary levels of miR- 1915 with proteinuria (r = 0.95; p = 0.003)
Positive correlation of urinary levels of miR-663 with proteinuria (r = 0.45; p = 0.04)
Plasma Positive correlation of plasma levels of miR-342 and urine levels of miR-155 with proteinuria (r = 0.73; p = 0.02 and r = 0.72; p = 0.03, respectively) in patients with FSGS
Upregulation of plasma levels of miR-30b, miR-30c, miR-34b, miR-34c and miR-342 and urine levels of mir-1225-5p in patients with MCD compared to patients with FSGS and controls (p < 0.001)
25218681 Zhang 2015 Plasma Initial screening stage: 9 FSGS w/proteinuria,
9 HC
  qRT-PCR Overexpression of in miR-125b, miR-186, and miR-193a-3p levels were identified and confirmed in FSGS
AUC of miR-125b, miR-186, miR-193a-3p, and the three miRNAs in combination were 0.882, 0.789, 0.910, and 0.963, respectively
Downregulation of miR-125b and miR-186 concentrations in FSGS patients in complete remission compared to those with nephrotic proteinuria
Confirmation stage: 32 FSGS w/proteinuria,
30 HC
37 FSGS w/proteinuria
35 CR FSGS
miR-125b and miR-186 levels declined markedly in patients with FSGS with complete remission, but not those with no response after steroid treatment.
Plasma miR-125b and miR-186 levels were not elevated in patients with membranous nephropathy and diabetic nephropathy regardless of degree of proteinuria
Plasma miR-186, but not miR-125b, level was correlated with degree of proteinuria in patients with FSGS (151 samples)
Prospective: 51 FSGS
w/proteinuria,
88 DC
2.3E + 07 Wang 2013 Urine 20 DGS
21 MCN/FSGS
23 MGN
10 HC
  qRT-PCR Urinary miR-29a, miR-192 and miR-200c were not differentially expressed in patients with different causes of nephrotic syndrome
Urinary sediment miR-29a, miR-192, and miR-200c levels were significantly different between diagnosis groups
Downregulation of urinary miR-638 in all causes of nephrotic syndrome than HC
Downregulation of urinary miR-192 in the DGS group
Overexpression of urinary miR-200c in the MCN/FSGS group
22960330 Szeto 2012 Urine 17 IgAN
17 DGS
22 HTN
Asian qRT-PCR Downregulation of urinary miR-15 in DGS patients
Overexpression of urinary miR-17 in patients with IgA nephropathy
Trend to overexpression of urinary miR-216a and miR-21 in hypertensive nephrosclerosis
  Positive correlation of the rate of eGFR decline with the urinary expression of miR-21 (r = 0.301; p = 0.026) and miR-216a (r = 0.515; p < 0.0001) when all patients were pooled
Separately, urinary miR-216a expression correlated with the rate of GFR decline in hypertensive nephrosclerosis (r = 0.588; p = 0.005) and diabetic glomerulosclerosis (r = 0.605, p = 0.010), but not IgA nephropathy (r = 0.042; p = 0.9).
Urinary miR-21 expression did not correlate with the rate of eGFR decline for any diagnosis group
Overexpression of urinary miR-21 and miR-216a was associated with dialysis-free survival in 18 patients who progressed to ESRD (log rank test, p = 0.005 and p = 0.003, respectively)
23272089 Wang 2012 Urine 10 FSGS Asian qRT-PCR Overexpression of urine miR-10a and miR-30d in FSGS patients (≈ 13- and tenfold, respectively)
Overexpression of urinary kidney-enriched miR-10a and miR-30d clearly indicated the kidney injuries in FSGS patients
22362909 Serino 2011 PBMC Initial sample cohort: 25 IgAN, 25 HC Italian AgilentHuman miRNAMicroarraysV2/qRT-PCR Thirty-seven miRNAs differentially expressed in PBMCs in IgA nephropathy
Upregulation of miR-148b in IgA nephropathy
Disease controls: 3 MPGN-I, 5 FSGS, 10 HSPN
Validation cohort: 50 IgAN,  50 HC
23313053 Wang 2011 Urine 43 IgAN Asian qRT-PCR Overexpression of both intra-renal and urinary of miR-146a and miR-155 IgAN
Urinary levels of both miR-146a and miR-155 positively correlated with proteinuria but neither of them correlated with eGFR (r = 0.074 and r = -0.198, respectively)
20364043 Wang 2010 Urine 43 IgAN Asian qRT-PCR Downregulation of urinary miR-200a, miR-200b and miR-429 in IgAN
Proteinuria significantly correlated with urinary expression
of miR-200a (r = -0.483; p < 0.001), miR-200b (r = -0.448, p = 0.001) and miR-429 (r = -0.466, p = 0.001)
eGFR significantly correlated with urinary expression of miR-200b (r = 0.512; p < 0.001) and miR-429 (r = 0.425, p = 0.005), but not miR-200a (r = 0.246, p = 0.112).
The rate of eGFR decline had a modest but significant correlation with urinary expression of miR-200b (r = 0.316, p = 0.041)
  1. AUC: Area under the receiver operating characteristic curves; CR: complete remission; DC: disease controls; DGS: diabetic glomerulosclerosis; eGFR: estimated glomerular filtration rate; ESRD: end-stage renal disease; FSGS: focal segmental glomerulosclerosis; HC: healthy controls; HTN: hypertensive nephropathy; IgAN: IgA nephropathy; MCD: minimal change disease; MCN: minimal change nephropathy; MGN: membranous glomerulonephritis; miRNA(s) microRNA(s); mRNA: messenger ribonucleic acid; PBMC: peripheral blood mononuclear cells; qRT-PCR: quantitative real-time polymerase chain reaction