Table 9.
miRNA studies in primary glomerulonephritis
| 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 |
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| 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) |
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| 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) |
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| 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) |
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| 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) |
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