Study / Animal Model / Drug / Renal effects
GLP-1R agonists
Hirata1 / Salt-sensitive obese db/db mice;
angiotensin II induced hypertensive C57BLK6/J mice / Exendin-4 / P / 1) FE-sodium ↑
P / 2) Angiotensin II induced hypertension ↓
Rieg2 / C57BL/6 (wild type) mice, GLP-1R–/– and diabetic db/db mice / Exendin-4 / P / GFR ↑, diuresis ↑, FE-sodium ↑ and NHE-3 expression ↑ in wild type but not in GLP-1R–/– mice. Diuresis ↑ and FE-sodium ↑ in db/db mice
Park3 / db/db mice / Exendin-4 / M / Albuminuria ↓,
H / Glomerular hypertrophy ↓, mesangial matrix expansion ↓, TGF-β1 expression ↓, collagen accumulation ↓, inflammatory cell infiltration ↓, apoptotic glomerular cells ↓
Kodera4 / STZ diabetic Sprague-Dawley rat / Exendin-4 / P / Glomerular hyperfiltration ↓
M / Albuminuria ↓, ICAM-1/collagen type 4 levels ↓, oxidative stress markers ↓, NF-κB ↓
H / Glomerular hypertrophy ↓, mesangial matrix expansion ↓, macrophage infiltration ↓
Hendarto5 / STZ diabetic Wistar rats / Liraglutide / M / Urinary 8-OHdG excretion ↓, urinary MDA excretion ↓, albuminuria ↓, renal oxidative stress markers ↓ (TGF-β1 / fibronectin)
Ojima6 / STZ diabetic Wistar rats / Exendin-4 / M / Albuminuria ↓, AGE-induced RAGE expression ↓, urinary 8-OHdG excretion ↓
H / Histopathologic renal changes ↓
DPP-4 inhibitors
Rieg2 / C57BL/6 (wild type) mice, GLP-1R–/– and diabetic db/db mice / Alogliptin / P / Diuresis ↑ and FE-sodium ↑ in wild type and GLP-1R–/– mice, no effect in db/db mice
Vaghasiya7 / STZ diabetic Wistar rats undergoing ischaemia/reperfusion / Sitagliptin / M / Lipid peroxidation ↓, xanthine oxidase activity ↓, MPO activity ↓, nitric oxide levels ↓, glutathione ↑, SOD ↑, catalase ↑
H / Apoptosis ↓, preservation of renal morphology
Liu8 / STZ diabetic Sprague-Dawley rats / Vildagliptin / P / Creatinine clearance ↑
M / Albuminuria ↓,TGF-β1 expression ↓, urinary cAMP excretion ↑, urinary 8-OHdG excretion ↓
H / Interstitial expansion ↓, glomerulosclerosis ↓, thickening of GBM ↓
Alter9 / STZ diabetic eNOS–/– C57BL/6J mice / Linagliptin / M / TNF-↓, combined with telmisartan: albuminuria ↓
H / Glomerulosclerosis ↓
Mega10 / ZDF rats / Sitagliptin / P / No change in creatinine and urea levels
M / Lipid peroxidation ↓
H / Glomerular lesions ↓ (fibrosis, sclerosis, mesangial expansion, atrophy, basement membrane atrophy), tubulointerstitial lesions ↓ (hyaline cylinders, tubular degeneration, basement membrane irregularity), vascular lesions ↓ (hyalinosis)
Wang11 / ZDF rats / 1) Vildagliptin
2) NWT-03 (inhibitor of both ACE and DPP-4) / M / 1 + 2) IL-1β↓, IL-13 ↓
2) TNF-↓, albuminuria ↓
H / 1 + 2) glomerulosclerosis ↓
Tofovic12 / ZSF1 rats (lean versus obese) / Sitagliptin / P / Angiotensin II induced renal vasoconstriction ↑
Abbreviations: 8-OHdG, 8-oxo-2-deoxyguanosine; ACE, angiotensin-converting enzyme; AGE, advanced glycation end-product; cAMP, cyclic adenosine monophosphate; FE, fractional excretion; ICAM, intercellular adhesion molecule; H, histology; IL, interleukin; M, biomarkers; MPO, myeloperoxidase; NF-κB, nuclear factor κ-B; P, physiology; SOD, superoxide dismutase; TGF, transforming growth factor; TNF, tumour necrosis factor; ZDF, zucker diabetic fatty; STZ, streptozotocin.
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