Table 3.
Role of urinary exosomal miRNA and mRNA as biomarkers for DN
| Level | Type of diabetes | Species | No. of participants case/(control) | Detection method of miRNA/mRNA | Comparing groups | Disease condition | Ref | ||
|---|---|---|---|---|---|---|---|---|---|
| miRNA | miR-145-5p, miR-27a-3p | ↑ | Type 2 | Human | 20/(20 DM, 20 HC) | RT-qPCR | DKD group vs. DM group and healthy control | UACR > 30 mg/g | [88] |
| miRNA-615-3p | ↑ | Type 2 | Human | 42/(21 DM, 20 HC) | RT-qPCR. | DKD group vs. DM group and healthy control | UACR > 30 mg/g | [89] | |
| miR-92a-1-5p | ↑ | Type 2 | Human | 44/(36) |
RNA sequencing, RT-qPCR |
DN vs. healthy control | eGFR ≥ 30 ml/min/1.73m2 | [38] | |
| miR663a | ↓ | Type 2 | Human | 5 PDKD, 4 NPDKD, 5 DM, 3 HC | RT-qPCR | PDKD vs. NPDKD vs. DM vs. HC | eGFR < 60 ml/min/1.73m2; 24-h urine protein excretion of ≥ 500 mg | [90] | |
| miR-103a-3p, miR-151a-5p, miR-191-5p, miR-1972, miR-22-3p, miR-24-3p, miR-26a-5p, miR-30d5p, miR-361-5p, miR-378a-3p, miR-4454, miR-200c-3p, miR-619-5p, let-7i-5p, miR-574-3p | ↑ | Type 2 | Human | 9/(9) | Microarray Analysis, Taqman qPCR | DN vs. DM without kidney disease | ……… | [63] | |
| miR-126, miR-155, miR-146 | ↑ | Type 2 | Human | 30/(34 DM, 28 HC) | Taqman qPCR | Patients with albuminuria vs. healthy controls and patients without albuminuria. | Urinary albumin > 30 mg/L | [91] | |
| miR-4534 | ↑ | Type 2 | Human | 17/(17) |
Microarray Analysis, RT-qPCR |
DKD vs. DM | Urinary microalbuminuria ≥300 mg/24 h | [92] | |
| miR-19b-3p | ↑ | Type 2 | Human | 28/(15) | RT-qPCR | DN vs. DM |
Biopsy-proven ACR> 30 mg/g; eGFR < 60 ml/min/1.73m2 |
[39] | |
| miR-188-5p, miR-150-3p, miR-760, miR-3677-3p, miR-548ah-3p, miR-548p, miR-320e, and miR-23c | ↑ | —– | Human | 6 DKD |
Next-generation sequencing. (small RNA sequencing) |
Nephrotic DKD at different stage, and non-diabetic CKD patients as control | UPCR > 300 mg/g | [93] | |
| miR-133a-3p and miR-153-3p | ↓ | ||||||||
| miR-21-5p, let-7e-5p and miR-23b-3p | ↑ | Type 2 | Human | 14/(15) | RT-qPCR | DKD vs. DM with normal renal function |
UACR > 3 mg/mmol; eGFR < 60 ml/min/1.73m2 |
[94] | |
| miR-30b-5p and miR-125b-5p | ↓ | ||||||||
| let-7c-5p | ↑ | Type 2 | Human | 28/(20 DM; 15 HC) | RT-qPCR | DKD group vs. DM group and healthy control |
ACR>25 mg/mmol; eGFR < 60 ml/min/1.73m2 |
[95] | |
| miR29c-5p and miR-15b-5p | ↓ | ||||||||
| miR-362-3p, miR-877-3p, and miR-150-5p | ↑ | Type 2 | Human |
5/(5) Verification 20/(20) |
RT-qPCR | DM with macroalbuminuria vs. DM with normoalbuminuria |
ACR>25mg/mmol AER=300–800 mg/24 h eGFR < 60 ml/min/1.73m2 |
[96] | |
| miR-15a-5p | ↓ | ||||||||
| miR-451-5p | ↑ | Type 1 | Rat | ……. | RT-qPCR | Diabetic rats after 6 weeks vs. 9 weeks vs. non-diabetic rats | ……. | [97] | |
| miR-133b, miR-342, miR-30a | ↑ | Type 2 | Human | 44 Ma/66 Mi/56 No/54 HC | RT-qPCR | Ma vs. Mi vs. No vs. HC | UACR > 30 mg/g | [98] | |
| miR-15b, miR-34a, miR-636 | ↑ | Type 2 | Human | 90/(46 DM; 44 HC) | Syber green-based PCR array; RT-qPCR | Patients with albuminuria vs. healthy controls and patients without albuminuria. | UACR > 30 μg/mg | [99] | |
| miR-320c | ↑ | Type 2 | Human |
(5 Mi; 3 No)/(8 DM; 8 HC) Verification 5 Mi/(6 DM; 6 HC) |
RT-qPCR | DN group (No, Mi) vs. DM group and healthy control | UACR > 30 mg/g; eGFR < 60 ml/min/1.73m2 | [49] | |
| miR-130a and miR-145 | ↑ | Type 1 | Human Mice | 12/(12) | Taqman qPCR |
Microalbuminuria vs. Normoalbuminuria Diabetic vs. non-diabetic mice |
AER> 20 μg/min; ACR>25 mg/mmol | [100] | |
|
miR-155 and miR-424 miR-145 |
↓ ↑ |
||||||||
|
miR-144–3p, miR-26a-5p, and miR-30c-5p miR-31–5p, miR-200c-3p, and miR-671–5p |
↑ ↑ |
Type 1 | Human |
8/(5) 17/(18) |
Next-generation sequencing. (small RNA sequencing) |
Overt vs. No PMA vs. IMA |
AER> 200 μg/min AER> 20–200 μg/min; |
[101] | |
| hsa-miR-320b, hsa-miR-30d-5p, hsa-miR-30e-3p, hsa-miR-30c-5p, hsa-miR-190a-5p, hsa-miR-29c-5p, hsa-miR-98–3p, hsa-miR-331–3p, hsa-let-7a-3p, hsa-miR-106b-3p, hsa-miR-30b-5p, hsa-miR-99b-5p, and hsa-let-7f-1–3p | ↓ | Type 1 | Human | 5/(4) | Paired-end sequencing (small RNA sequencing) | DKD group vs. healthy control | eGFR < 60 ml/min/1.73m2; UACR > 30 mg/g | [102] | |
| mRNA | UMOD mRNA | ↑ | Type 2 | Human | 44 Ma/66 Mi/56 No/54 HC | RT-qPCR | Ma vs. Mi vs. No vs. HC | UACR > 30 mg/g | [68] |
| 19 Mild DKD; 15 sever DKD; 11 CKD; 166 DM;18 OC; 18 HC | Mild DKD vs. sever DKD vs. CKD vs. DM vs. OC vs. HC |
ACR> 30 mg/g; eGFR < 60 ml/min/1.73m2 |
[103] | ||||||
| SLC12A1 mRNA, NDUFB2 mRNA | ↑ | Type 2 | Human | 19 Mild DKD; 15 sever DKD; 11 CKD; 166 DM;18 OC; 18 HC | RT-qPCR | Mild DKD vs. sever DKD vs. CKD vs. DM vs. OC vs. HC |
ACR> 30 mg/g; eGFR < 60 ml/min/1.73m2 |
[103] | |
| CCL21 mRNA | ↑ | Type 2 | Human | 32/(19 DM, 20 HC) | RT-qPCR | DN group vs. DM group and healthy control |
Biopsy-proven UACR > 30 mg/g |
[104] | |
| WT-1 mRNA | ↑ | Type 2 | Human | 10/(5) | RT-qPCR | Overt DN vs. healthy control | 24h urinary protein> 3g/day | [105] | |
| MAP7, MSRB1, GPX3, IL32, NOX4, HRSP12, TINAG, CAPN3, CXCL14, MSRA, CRYAB, RBP5, and TMEM9 | ↑ | Type 1 | Human | 17/(37) | Genome-wide sequencing (mRNA sequencing) | Macroalbuminuria vs. Normoalbuminuria | AER> 30 mg/day | [106] |
HC Healthy control, DN diabetic nephropathy, DM diabetes mellitus, PDKD proteinuria diabetic kidney disease, NPDKD non-proteinuria diabetic kidney disease, UACR urinary albumin to creatinine ratio, eGFR estimated glomerular filtration rate, AER albumin excretion rate, UPCR urinary protein to creatinine ratio, No normoalbuminuria, Mi microalbuminuria, Ma macroalbuminuria, PMA persistent microalbuminuria, IMA intermittent microalbuminuria, OC obese control