Kidney Week

Abstract: FR-PO239

The GLP-1R Agonist Liraglutide and Its Hypotensive and Natriuretic Effect in Diabetic CKD

Session Information

• Diabetic Kidney Disease: Advancing Treatment
  November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 602 Diabetic Kidney Disease: Clinical

Authors

• Wajdlich, Malgorzata Jadwiga, Medical Univercity in Lodz, Lodz, Poland

Malgorzata Jadwiga Wajdlich,

• Nowicki, Michal P., Medical Univercity in Lodz, Lodz, Poland

Michal P. Nowicki,

Background

The impaired sodium excretion with fluids retention, high activity of renin-angiotensin-aldosterone system (RAAS) are dominant pathogenetic factors in the development of hypertension in diabetic kidney disease. The GLP-1R agonist-liraglutide is an antidiabetic drug that has showed blood pressure lowering effect most probably mediated by increased natriuresis and inhibition of RAAS.
The aim of the study was to investigate the hypotensive and nariuretic effect of a single dose of liraglutide compared to placebo in patients with type 2 diabetes mellitus and impaired renal function.

Methods

The study included 17 patients with eGFR below 30, and 17 patients with eGFR above 60 ml/min/1.73 m². In a cross-over study each subject received in a random order a single subcutaneous dose of 1.2 mg liraglutide and placebo with subsequent 24h blood pressure monitoring and 24h urinary samples collection to assess natriuresis. Before and after each medication the blood samples were collected to measure the serum concentration of renin, aldosterone and atrial natriuretic peptide (ANP).

Results

After 1.2 mg liraglutide 24h MAP increased from 97.8±8.1 to 102.4±8.6 mmHg, p=0.003 compared to placebo in patients with eGFR below 30 ml/min/1.73 m². In patients with eGFR >60 ml/min/1.73 m² no significant change of blood pressure was revealed. After liraglutide mean 24h urine sodium excretion increased in both groups (p=0.003) but the increase was significantly larger in patients with eGFR >60 ml/min/1.73 m² p=0.046. The difference of mean 24h sodium excretion between liraglutide and placebo correlated negatively with a difference of 24 mean arterial pressure (r=-0.7 p=0.01) in the group with eGFR >60 ml/min/1.73 m². The concentration of ANP increased after injection of liraglutide compared with placebo in both groups, but the increase was significantly larger in patients with worse kidney function (p=0.012). In the same group with eGFR <30 ml/min/1.73 m² significant decrease of the serum concentration of aldosterone was noted after liraglutide (p=0.013).

Conclusion

Liraglutide administration in the patients with advanced CKD may cause a transient increase of systemic blood pressure due to reduced natriuretic effect. The natriuretic effect of liraglutide in diabetic kidney disease depends on increased atrial natriuretic peptide and decreased aldosterone secretion.