Table 5.

Animal studies evaluating the potential reno-protective effects of vardenafil.

Reference/ Country/Year	Studied Animal	AKI Model	PDE5I Route	Timing	Sample	AKI Renal Effects	PDE5I Renal Effects	Outcome
[45]/ Turkey/2011	Wistar albino rats	UUO model	Sildenafil-orally-1 mg/day Vardenafil-orally-0.5 mg/day Tadalafil-orally-10 mg/72 h For 30 days	POST	30 days	↑Tubular cell apoptosis ↑eNOS ↑ iNOS	↓Tubular cell apoptosis ↓ eNOS ↓iNOS Sildenafil better results	POS
[77]/ Greece/2013	Male Wistar rats	IR renal injury model	Vardenafil Intravenously 0.02, 0.2, 2, 20 μg/kg 1 h pre-operatively or 2μg/kg 45 min post occlusion	PRE or POST	Blood samples and right nephrectomy 4 h post ischemia	Edema Loss of brush border Nuclear condensation	↓sCr (0.2, 2, 20 μg/kg) No change when given post-ischemia ↓FENa, ↑Renal uptake of tracer ↑cGMP, ↑ERK 1/2 phosphorylation Renoprotection (in scintigraphy) Significant improvement in all histo-logical changes irrespectively of dose	POS
[78]/ Brazil/2015	Male Wistar rats	IR renal injury model	Vardenafil Solution in a probe (1 mg/mL in 10 mg/kg) 1 h prior the ligation	PRE	Left nephrectomy Cytophotometry 24 h after reperfusion	↑Cleaved caspase-3 ↑sCr ↑Vacuolar degeneration	↓ Cleaved caspase-3 ↓ Vacuolar degeneration	POS

Abbreviations: AKI, acute kidney injury; cGMP, cyclic guanosine monophosphate; eNOS, endothelial NOS; ERK, extracellular signal-regulated kinase; FeNa, fractional excretion of sodium; IR, ischemia/reperfusion; iNOS, inducible NOS; PDE5I, phosphodiesterase 5 inhibitor; sCr, serum creatinine; UUO, unilateral ureteral obstruction; ↓, reduced; ↑, increased.