Glucagon and GLP-1 in hemodialysis: associations with mortality and nutritional decline

BACKGROUND: Glucagon is a key regulator of amino acid metabolism, and elevated levels are frequently observed in maintenance hemodialysis (MHD) patients. Yet, the relationship between plasma glucagon levels, nutritional parameters, and prognosis in MHD patients remains unclear. We evaluated whether glucagon levels in MHD patients are associated with normalized protein catabolic rate (nPCR), glucagon-like peptide-1 (GLP-1), nutritional status, and all-cause mortality. METHODS: In this prospective observational study, plasma hormone levels were measured alongside clinical, biochemical, anthropometric, bioimpedance-derived nutritional markers, and inflammatory indices. Mortality was assessed using Kaplan-Meier and Cox regression analyses. RESULTS: This study included 82 prevalent MHD patients. Patients were followed for 18.0 ± 4.9 months. Glucagon correlated positively with nPCR (r = 0.25, p = 0.03) and inversely with phase angle (PhA) (r = - 0.24, p = 0.03) after adjustment. Additional correlations with GLP-1 became marginal after adjustment. The subgroup with high glucagon and low nPCR showed the lowest PhA (p = 0.03), and remained significant after multivariable adjustment. Patients with glucagon ≥ 120 pg/mL (ROC-derived cutoff) had higher mortality (log-rank p = 0.05); however, the discriminative power of this cutoff was limited (AUC 0.63). In multivariable models, the association persisted after adjustment for age and diabetes but was attenuated after further controlling for PhA, GLP-1, or MIS. CONCLUSION: Elevated glucagon in MHD patients was modestly associated with altered protein metabolism, impaired nutritional integrity, and borderline higher all-cause mortality. The independent prognostic value of glucagon remains uncertain, and a concept of a glucagon resistance phenotype is speculative.