High-dose liraglutide impairs kidney function in hypertensive female rats through oxidative stress and fibrosis | Research

The takeaway

In female hypertensive rats, high-dose liraglutide (0.6 mg/kg) caused renal injury markers elevation, increased collagen deposition, aberrant GFR increase, and altered nitric oxide metabolism, while low-dose (0.06 mg/kg) was protective—independent of BP or glucose.

Dose-dependent kidney risk
High-dose liraglutide damaged kidneys while low-dose protected them in female hypertensive rats—challenging the assumption of uniform GLP-1 renoprotection

What the researchers found

High dose (0.6 mg/kg): ↑BUN, ↑BUN/Cr, ↑collagen deposition, aberrant ↑GFR, ↑nitrate, ↓nitrite, ↑urinary Na/K ratio. Low dose (0.06 mg/kg): ↓APOP (protective). Both: ↓weight, BP/glucose independent. Female SHR model, 30 days.

Why it matters

GLP-1 drugs are generally considered renoprotective. This study reveals a dose-dependent toxicity in hypertensive females that could have clinical implications for high-dose prescribing in this population.

How the study worked

Female SHR rats treated 30 days, 2x daily. Saline, low-dose (0.06 mg/kg), or high-dose (0.6 mg/kg) liraglutide. 24h volume monitoring. Renal tissue: nitrite/nitrate, APOP, collagen, Cr, U, Na, K.

What this study cannot tell us

Rat model (SHR). Doses may not directly translate to human clinical doses. 30-day study. Female-only. Aberrant GFR increase mechanism not fully explained.

How to read the evidence

Preclinical rat study. Important safety signal but limited to one model.

When this study was published

Published in 2025.

The bigger picture

This challenges the assumption that GLP-1 drugs are uniformly renoprotective. Dose matters, sex may matter, and hypertension may modify the renal response—important caveats for clinical use.

Questions still open

Are high-dose GLP-1 drugs safe for hypertensive women's kidneys?
Does the dose-response differ in male vs female hypertension?
Should renal function be monitored more closely at higher GLP-1 doses?

Common questions

Can high doses of GLP-1 drugs harm the kidneys?

In this rat study, high-dose liraglutide caused kidney fibrosis and altered kidney function in hypertensive females, while low doses were protective. This suggests dose matters for kidney safety, especially in hypertensive individuals.

Should I worry about my kidneys on liraglutide?

At standard clinical doses, GLP-1 drugs are generally kidney-protective. However, this study raises a flag for very high doses in hypertension. Your doctor should monitor kidney function during treatment, and dose escalation should follow recommended guidelines.

Read the original research

High Dose of Liraglutide Impairs Renal Function in Female Hypertensive Rats.

Journal of cardiovascular pharmacology, 85(2), 120-128

View on PubMed ↗Publisher’s paper ↗

Citation

Tonon Firmino, Felipe; Peixoto, Pollyana; Batista, Thatiany Jardim; Escouto, Leonardo da Silva; Brasil, Girlandia Alexandre; Couto, Mariana Dos Reis; de Melo Júnior, Antonio Ferreira; Bissoli, Nazaré Souza. (2025). High Dose of Liraglutide Impairs Renal Function in Female Hypertensive Rats.. Journal of cardiovascular pharmacology, 85(2), 120-128. https://doi.org/10.1097/FJC.0000000000001649