High Dose of Liraglutide Impairs Renal Function in Female Hypertensive Rats

Glucagon-like peptide-1 receptor agonists exhibit beneficial cardiovascular effects. However, the renal effects of different doses of liraglutide in an essential hypertension model have not yet been investigated. Female spontaneously hypertensive rats were treated for 30 days, twice a day, with saline (control) or liraglutide at low (0.06 mg/kg) and high (LH, 0.6 mg/kg) doses. Volume intake and excretion were monitored for a period of 24 hours. In renal tissue, nitrite, nitrate, advanced protein oxidation products, collagen deposition, creatinine (Cr), urea (U), sodium, and potassium were analyzed. Liraglutide reduced body weight gain in both groups. However, in the high dose, it increased urinary volume excretion and sodium/potassium ratio. Both doses reduced the urinary U/Cr ratio and LH increased the serum U/Cr ratio. Advanced protein oxidation products were reduced only in low liraglutide. LH augmented collagen and early markers of kidney injury (blood urea nitrogen, blood urea nitrogen/Cr). LH increased nitrate, reduced nitrite, and caused an aberrant increase in glomerular filtration rate. Both doses' effects were independent of blood pressure and glycemic control. Liraglutide appears to have distinct effects on the hypertensive female kidney depending on the dose, with higher doses impairing kidney function.