Table 2.
Role of urinary exosomal protein as biomarkers for DN
| Protein | Level | Type of diabetes | Species | No. of participants case/(control) | Detection method of exosomal protein | Comparing groups | Disease condition | Ref | |
|---|---|---|---|---|---|---|---|---|---|
| TF | Transferrin | ↑ | Type 2 | Human | 15 DM 3, 36 DM2, 74 DM 1, 19 HC |
LC-MS/MS Western blot |
DKD (DM 3, DM 2) vs. DM 1 vs. HC | ACR> 30 mg/g | [77] |
| SERPINA1 | Alpha-1 antitrypsin | ↑ | |||||||
| AFM | Afamin | ↑ | |||||||
| CTSD | Cathepsin D | ↓ | |||||||
| PHYHD1 | Phytanoyl-CoA dioxygenase domain containing 1 | ↑ | Type 2 | Human | 20 DN, 20 NDRD, 16 T2DM, 21 HC |
DIA-MS data acquisition. ELISA |
DN vs. NDRD vs. T2DM vs. HC | Kidney biopsy | [78] |
| PAK6 |
Serine/threonine-protein kinase Epidermal growth factor receptor |
↑ ↑ |
Type 2 | Human | 48/(48 T2DM, 48 HC) |
LC-MS/MS Western blot ELISA |
DN vs. T2DM and HC |
ACR> 30 mg/g; eGFR < 60 ml/min/1.73m2 |
[79] |
| EGF | Epidermal growth factor receptor | ↑ | |||||||
|
AMBP MLL3 |
α-microglobulin/bikunin precursor Histone-lysine N-methyltransferase |
↑ ↑ |
—– | Human | 8/(8) |
LC–MS/MS SRM |
DN vs. HC |
ACR> 30 mg/g. eGFR < 60 ml/min/1.73m2 |
[70] |
| MLL3 | Histone-lysine N-methyltransferase | ↑ | |||||||
| VDAC1 | Voltage-dependent anion-selective channel protein 1 | ↓ | |||||||
| Regucalcin (SMP30) | Senescence marker protein-30 | ↓ | Type 2 | Rat Human |
………. Urine 4/(3) Tissue 7/(4) |
2-dimensional DIGE Western blot, IHC, SRM |
STZ-induced diabetic rat with renal fibrosis vs. HC DN vs. HC |
eGFR < 60 ml/min/1.73m2 Urine protein excretion of ≥ 150 mg/24 h |
[80] |
| WT-1 | Wilm’s tumor-1 | ↑ | Type 1 | Human |
18/(30 DM, 25 HC) WT1 detected in 19 out of 31 |
Western blot Immunoblot |
T1DM with proteinuria vs. T1DM without proteinuria and HC T1DM |
ACR> 30 mg/g. Microalbumin >20 µg/min |
[81] [82] |
| PEPD | Xaa-Pro dipeptidase | ↑ | Type 2 | Rat | 7/(7) |
nLC-ESI-MS/MS Immunoblotting |
ZDF rats sacrificed after 12 weeks, 20 weeks vs. lean control | ...... | [83] |
| MUP-1 | Major Urinary Protein −1 | ↓ | |||||||
| AQP5, AQP2 | Aquaporins | ↑ | Type 2 | Human | 12 DN, 12 DM, 11 NDN, 7 HC |
ELISA Western blot |
DN vs. DM vs. NDN vs. HC | Biopsy-proven | [84] |
| UMOD | Uromodulin | ↑ | Type 2 | Human | 22 Ma, 32 Mi, 46 No, 31 HC | ELISA | Ma vs. Mi vs. No vs. HC | ACR> 30 mg/g | [85] |
| CD 63 | ↓ | —– | Human | 8 Mi, 13 No | Flow cytometry | Mi vs. No | UAER from 30,300 mg/24 h | [86] | |
| C-megalin | ↑ | Type 2 | Human | 19 Ma, 17 Mi, 20 No, 19 HC | Immunoblotting | Ma vs. Mi vs. No vs. HC | ACR> 30 mg/g | [87] |
HC Healthy control, DN diabetic nephropathy, DM diabetes mellitus, DKD diabetic kidney disease, ACR albumin to creatinine ratio, eGFR estimated glomerular filtration rate, AER albumin excretion rate, No normoalbuminuria, Mi microalbuminuria, Ma macroalbuminuria, SRM selected reaction monitoring, LC-MS/MS liquid chromatography-tandem mass spectrometry, DIGE two-dimensional difference gel electrophoresis, IHC immunohistochemistry, ZDF Zucker diabetic fatty rats, NDN non-diabetic nephropathy