Table 2.
Biochemical and Histological Phenotypes in Translation Animal Models of T2D-DKD
| Type | Animal Model | Treatment | Strain | Ob | HBS | HBP | HTC | HC | PRO | Early Glomerular Pathology | Advanced Glomerular Pathology | TIF | GFR (#) | Ref. | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mesangial Matrix Expansion | GBM Thickening | Fibrosis or Mild Sclerosis | Nodular/Diffuse Sclerosis | Arterial Hyalinosis | |||||||||||||
| Chemical | Mice | STZ + NAD | B6 | - | + | NA | NA | NA | + | + | + | + | - / - | - | + | - | [53,54] |
| Rats | STZ + NAD | Wistar | - | + | NA | ± | ± | + | + | + | + | - / - | - | + | - | [55–61] | |
| Dietary | Mice | HFD | B6 | + | + | + | + | + | + | + | + | - | - / - | - | - | - | [64,67–69] |
| Chinese Bama minipigs | HsuHF or HFHsuHC | + | ± | NA | + | + | + | + | + | + | - / - | - | + | - | [71,72] | ||
| Chemical + Dietary | Mice | STZ + HFD | B6 | ± | + | NA | + | + | + | + | + | + | - / - | - | + | - | [80–87] |
| Rats | STZ + HFD | SD, Wistar | ± | + | NA | + | ± | + | + | + | + | - / - | - | - | - | [76–79] | |
| Surgical + Chemical + Dietary | Mice | UNx + STZ + HFD | B6 | NA | + | NA | NA | NA | + | + | + | + | - / - | + | + | - | [92] |
| Rats | UNx + STZ + HFD or UNx + STZ + NAD + HFD | SD, Wistar | ± | + | ± | + | + | +a | + | + | + | - / ± | - | ± | - | [32,91] | |
| Spontaneous | OLETF rats | OLETF | + | + | ± | + | + | +a | + | + | + | + / - | - | + | - | [93–96] | |
| GK rats | GK | - | + | - | - | - | ± | + | + | + | - / - | - | + | - | [103–105] | ||
| DOCA or Angǁ + HSaD | - | + | + | - | - | + | + | + | + | - / - | - | + | - | [103,106] | |||
| HFD | - | + | - | - | - | ± | + | + | + | - / - | - | + | - | [107] | |||
| Genetic | ob/ob mice | BTBR | + | + | - | + | + | +a | +b | + | + | ± / + | + | ± | - | [110] | |
| HPD | + | + | - | + | + | +a | +b | + | + | ± / + | + | + | - | [111] | |||
| db/db mice | BKS | + | + | - | + | + | +a | + | + | - | - / - | ± | - | - | [116–119,122] | ||
| HPD | + | + | NA | + | + | +a | + | + | + | - / - | ± | + | - | [121] | |||
| UNx | + | + | - | + | + | +a | + | + | + | - / - | - | + | + | [122,123] | |||
| DBA/2J | + | + | NA | + | + | +a | + | + | + | - / - | - | - | - | [117] | |||
| FVB | + | + | NA | + | + | + | + | + | + | - / - | - | + | - | [124] | |||
| CD1 | + | + | - | NA | NA | +a | + | + | + | -/+ | - | + | + | [115] | |||
| ZDF rats | ZDF | + | + | ± | + | + | +a | + | + | + | - / - | - | + | - | [125,127–130] | ||
| HFD | + | + | ± | + | + | +a | + | + | + | - / - | - | + | - | [130,131] | |||
| ZSF1 rats | ZDF × SHHF | + | + | + | + | + | +a | + | + | + | - / ± | + | + | +b | [133–135] | ||
| KKAy/Ta mice | KK/Ta | + | + | - | + | + | + | + | + | + | - / - | - | + | - | [138–140] | ||
| HFD | + | + | - | + | + | + | + | + | + | - / - | - | + | - | [138] | |||
| T2DN rats | T2DN/Mcwi | - | + | - | + | + | +a | + | + | + | + / + | + | + | +b | [142–144] | ||
Notes: +, positive; -, negative; ±, weakly positive or inconsistent results; NA, not available; a, > 10-fold; b, > 50%; #, vs normal value.
Abbreviations: T2D-DKD, type 2 diabetic kidney disease; Ob, Obesity; HBS, high blood sugar; HBP, high blood pressure; HTG, high triglycerides; HC, high cholesterol; PRO, Proteinuria; GMB, glomerular basement membrane; TIF, tubulointerstitial fibrosis; GFR, glomerular filtration rate; Ref., references; STZ, streptozotocin; UNx, uninephrectomy; NAD, nicotinamide; HFD, high-fat diet; HsuHF, high-sugar-high-fat diet; HFHsuHC, high-fat-high-sugar-high-cholesterol diet; Angǁ, angiotensinǁ; DOCA, deoxycorticosterone acetate; HSaD, high-salt diet; HPD, high-protein diet.