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Semaglutide is an antidiabetic drug analogous to human GLP-1 (glucagon-like peptide), a class of drugs that has recently stood out thanks to its good results in clinical trials, however, the scarcity of data of its effects on chronic and acute cardiovascular and kidney diseases limits its use for the general public. Acute kidney injury (AKI) affects about 49% of patients undergoing major cardiovascular surgeries, in addition to a mortality rate higher than 50%, which justifies the search of new possibilities for the prevention of AKI. Objectives: To evaluate the effect of oral semaglutide on renal function in rats submitted to renal ischemia/ reperfusion animal model.
This is a descriptive, prospective, quantitative and experimental study with adult male Wistar rats, weighing 250-300g, randomized into the following groups: SHAM (control, with simulation of renal pedicle clamping); GLP-1 (semaglutide, orally-vo; 3mg/day; 5 days); Ischemia and Reperfusion (IR) (clamping of bilateral renal pedicles for 30 minutes, followed by reperfusion) and GLP-1+IR (semaglutide followed by IR). Renal function was evaluated by inulin clearance (Clin) , serum creatinine (Scr) and urinary flow rate (FU). The oxidative profile was evaluated by urinary peroxides (FOX), lipid peroxides (TBARS) and nitric oxide (NO)
The I/R group showed elevated serum creatinine, decreased urine flow rate, reduced Clin while the GLP-1+IR group showed increased Clin compared to the I/R group. In addition, the GLP-1+IR group showed a decrease in oxidative metabolites (FOX, TBARS and NO) when compared to IR.
Table 1; Renal Function
Groups
n
Urinary Flow (ml/min)
Serum creatinine (mg/dl)
Inulin Clearance (ml/min/100mg)
SHAM
5
0,013±0,002
0,31±0,06
0,81±0,06
GLP-1
0,030±0,013 a
0,51±0,1
0,75±0,13
IR
0,011±0,005 b
2,27±0,6 ab
0,24±0,03 ab
GLP-1+IR
0,015±0,060 b
0,95±0,31 ac
0,51±0,08 ab
Results expressed as mean±standard deviation. SHAM: Control group; GLP-1: Glucagon Like Peptide; I/R: Ischemia and Reperfusion;
a p<0,0001 vs SHAM
b p<0,0001 vs GLP-1
c p<0,0001 vs IR
d p<0,0001 vs GLP-1+IR
Table 2. Oxidative and antioxidant profile.
Grupos
Urinary peroxides (nmol/g de urinary creatinine)
Lipid peroxidation (mnol/g de urinary creatinine)
Urinary nitrate (nmol/g de urinare creatinine)
3,3±0,6
0,18±0,01
16,0±5,2
3,2±1,1
0,14±0,04
61,1±25,8a
15,9±2,8 ab
1,78±0,41 ab
174,5±13,0 ab
GLP-1 + IR
7,7±2,6 abc
0,20±0,05 c
68,0±20,1 ac
Results expressed as mean±standard deviation. SHAM: Control group; GLP-1: Glucagon Like Peptide; IR: Ischemia and Reperfusion;
Semaglutide presented a renoprotective effect associated with its antioxidant role that prevented the reduction in renal function caused by the ischemic AKI.