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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