Low-Plasma Insulin-Like Growth Factor-1 Associates With Increased Mortality in Chronic Kidney Disease Patients With Reduced Muscle Strength

Objectives: Chronic kidney disease (CKD) leads to metabolic and nutritional abnormalities including resistance to insulin-like growth factor-1 (IGF-1) action, and reduced muscle mass and strength. Low IGF-1 as well as low hand-grip muscle strength (HGS) are inde-pendent predictors of increased mortality in CKD patients.Methods: In 685 patients (CKD Stage 3-5, median age 58 years; 62% men), baseline measurements of IGF-1, HGS, subjective global assessment (SGA), lean body mass index (LBMI), and metabolic and inflammatory biomarkers potentially linked to IGF-1 were analyzed in relation to mortality during 5 years of follow-up. We compared survival in 4 groups with high or low (cut-offs defined by receiver oper-ating characteristic curve analysis) levels of IGF-1 and HGS. Results: Patients with low IGF-1 were older; had lower BMI, HGS, and LBMI, were more likely to have diabetes, cardiovascular dis-ease (CVD), and malnutrition (SGA .1); and had high-sensitivity C-reactive protein levels. During 5 years of follow-up, 208 patients died. The mortality rate was highest among patients with Low IGF-1 + Low HGS. In competing-risk regression analysis, Low IGF-1 + Low HGS was independently associated with 2.8 times higher all-cause mortality risk than Low IGF-1 + High HGS, after adjusting for Fra-mingham's CVD risk score, presence of CVD, SGA, dialysis status, high-sensitivity C-reactive protein, albumin, LBMI, and sample time in freezer. Conclusion: Low IGF-1 was associated with increased all-cause mortality in patients who also had low HGS but not in those with high HGS, suggesting that the association of IGF-1 with survival in CKD patients depends on nutritional status.