Background: Protein-energy wasting (PEW) is highly prevalent in haemodialysis (HD) patients and associated with increased mortality and cardiovascular disease (CVD). Insulin-like growth factor 1 (IGF-1) correlates to markers of PEW and CVD. Disturbances in the growth hormone axis in end-stage renal disease (ESRD) could have an impact on survival through increased PEW and CVD.
Methods: A cohort of 265 incident HD patients (median age 68 years, 59% males) was followed for 3 years. Subjects were categorized according to IGF-1 levels at dialysis initiation. Outcome and comorbidity data were retrieved from national registers. The Kaplan-Meier diagram and Cox proportional hazards model were used for the analysis of survival.
Results: Patients with IGF-1 levels in the lowest tertile were characterized by female sex, low creatinine, hypoalbuminemia and high C-reactive protein (CRP) levels. IGF-1 levels within the lowest tertile were associated with increased mortality [hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.7-3.4]. This association persisted when corrected for demographic factors (age, sex) and comorbidities (diabetes mellitus, CVD, heart failure) in multivariable analysis. Including high-sensitivity C-reactive protein (hs-CRP) and serum creatinine in the model had a small effect on the magnitude of the hazard. When serum albumin was added to the model, the HR declined from 2.2 to 1.6, but remained significant (P = 0.02).
Conclusion: Low IGF-1 levels associate with increased mortality in HD, independent of biomarkers of inflammation (hs-CRP) and PEW (creatinine, albumin). Serum albumin modulates the relationship between IGF-1 levels and mortality, indicating shared pathophysiological pathways with IGF-1.
Keywords: albumin; end-stage renal disease; inflammation; insulin-like growth factor 1; survival analysis.