Table 1.

Effects of levosimendan or its metabolite OR-1896 on renal tissue and/or function in in vivo animal experiments

Study	Animal model	Disease model	Comparator	Main levosimendan effects on renal tissue and/or function
Grossini [13]	Pig	Renal I/R	Levosimendan without or with Custodiol® vs placebo	Better protection against renal I/R injury in terms of antioxidant, anti-apoptotic and pro-survival actions, and improvement of renal function (creatinine clearance, plasma creatinine, microalbuminuria, albumin/creatinine ratio). Role of mitochondrial KATP channels and NO
Rehberg [42]	Sheep	Sepsis	Vasopressin and norepinephrine ± levosimendan	Improved renal function (surrogate parameters: creatinine, plasma urea, dieresis, urinary protein/creatinine ratio)
Yakut [23]	Rabbit	Renal I/R	Levosimendan vs placebo or iloprost	More pronounced reduction in renal I/R injury
Zager [14]	Mouse	Endotoxemic acute renal failure	Levosimendan vs placebo	Protection against endotoxemic acute renal failure due to vasoactive effects
Faivre [11]	Rabbit	Sepsis	Levosimendan with vasopressin vs levosimendan with norepinephrine	No altered systolic or diastolic renal blood flow or cortical or medullary perfusion
Oldner [12]	Pig	Sepsis	Levosimendan vs placebo	Renal blood flow unaffected
Pagel [10]	Dog	Healthy	Levosimendan vs pimobendan or milrinone	Greater increase in blood flow to the renal medulla and decreased renal medullary and cortical vascular resistance
Gecit [50]	Rat	Enzyme activities in healthy rats	Levosimendan vs placebo	Reduction of oxidative stress
Louhelainen [24]	Rat	Salt-induced hypertension	OR 1896 vs placebo	No effects on albuminuria or tissue morphology
Chew [51]	Pig	Sepsis	Levosimendan vs placebo	No effects on renal and liver function (serum creatinine, urea, bilirubin, AST, ALT)

I/R ischemia/reperfusion; Custodiol® multi-organ histidine-tryptophan-ketoglutarate preservation solution; NO nitric oxide; AST aspartate aminotransferase; ALT alanine aminotransferase