Glucagon Clearance is Decreased in Chronic Kidney Disease, but Preserved in Liver Cirrhosis

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posted on 2024-07-25, 17:57 authored by Magnus F. G. Grøndahl, Andreas H. Lange, Malte P. Suppli, Mira Thing, Lise L. Gluud, Dea H. Kofod, Mads Hornum, Gerrit Van Hall, Samuel A.J. Trammell, Trisha J. Grevengoed, Bolette Hartmann, Jens J. Holst, Tina Vilsbøll, Mikkel B. Christensen, Asger B. Lund, Filip K. Knop

Abstract It is not completely clear which organs are responsible for glucagon elimination in humans, and disturbances in the elimination of glucagon could contribute to the hyperglucagonemia observed in chronic liver disease and chronic kidney disease (CKD). Here, we evaluated kinetics and metabolic effects of exogenous glucagon in individuals with stage 4 CKD (n =16), individuals with Child-Pugh A-C cirrhosis (n = 16) and matched control individuals (n = 16), before, during and after a 60-minute glucagon infusion (4 ng/kg/min). Individuals with CKD exhibited a significantly lower mean metabolic clearance rate of glucagon (14.0 [95% CI 12.2;15.7] mL/kg/min) both compared to individuals with cirrhosis (19.7 [18.1;21.3] mL/kg/min, P < 0.001) and to control individuals (20.4 [18.1;22.7] mL/kg/min, P < 0.001). Glucagon half-life was significantly prolonged in the CKD group (7.5 [6.9;8.2] minutes) compared to individuals with cirrhosis (5.7 [5.2;6.3] minutes, P = 0.002) and control individuals (5.7 [5.2;6.3] minutes, P < 0.001). No difference in the effects of exogenous glucagon on plasma glucose, amino acids, or triglycerides was observed between groups. In conclusion, chronic kidney disease, but not liver cirrhosis leads to a significant reduction in glucagon clearance, supporting the kidneys as a primary site for human glucagon elimination. Article highlights · This study was undertaken to gain insights into the elimination of glucagon in humans, as this is an important, yet not fully uncovered part of glucagon physiology · We investigated whether individuals with chronic kidney disease or liver cirrhosis were characterized by an altered elimination of glucagon · We found that individuals with stage 4 chronic kidney disease exhibit a significantly reduced elimination of glucagon, while patients with liver cirrhosis have a preserved glucagon elimination · Our findings support the kidneys as the prevailing site of glucagon elimination in humans and shed light on glucagon-related pathophysiology in liver and kidney diseases