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Table 3 Role of urinary exosomal miRNA and mRNA as biomarkers for DN

From: Role of exosomes in pathogenesis, diagnosis, and treatment of diabetic nephropathy

  

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]