Association of growth differentiation factor-15 with muscle wasting and anemia in chronic kidney disease

Cachexia, characterized by muscle wasting and anemia, is a major complication of chronic kidney disease (CKD). Growth differentiation factor-15 (GDF-15), a stress-responsive cytokine implicated in cancer cachexia, is markedly elevated in CKD and linked to disease progression. However, the role of GDF-15 in CKD-related cachexia remains unclear.

We conducted a cross-sectional study of 268 patients with stage 3-5 CKD not yet on dialysis. Plasma GDF-15 concentrations were measured using immunoassays. Lean body mass was assessed by multifrequency bioimpedance spectroscopy with the Body Composition Monitor (BCM), and appendicular skeletal muscle mass (ASM) was estimated using a validated BCM-derived equation. Muscle wasting was defined as ASM index <7.0 kg/m² in men or <5.7 kg/m² in women, according to Asian Working Group for Sarcopenia criteria. Anemia was defined as hemoglobin <13 g/dL in men or <12 g/dL in women, based on KDIGO criteria. Associations of GDF-15 with muscle wasting and anemia, two core features of CKD cachexia, were examined using multivariable regression models.

Median plasma GDF-15 concentration was 2674 (range 550-12466) pg/mL. Higher GDF-15 was independently associated with lower lean tissue index and lower hemoglobin (both P < 0.001). Additional independent determinants of GDF-15 included age, male sex, diabetes, smoking status, eGFR, proteinuria, ferritin, and NT-proBNP. In multivariable logistic regression, each natural log increase in GDF-15 was associated with greater odds of both muscle wasting (OR 2.93, 95% CI 1.23-6.97, P = 0.015) and anemia (OR 3.45, 95% CI 1.09-10.91, P = 0.035).

Elevated GDF-15 is associated with muscle wasting and anemia in CKD independent of age, sex, comorbidities, and kidney function, mirroring its role in cancer cachexia. These findings suggest that GDF-15 may reflect pathophysiological processes linked to cachexia-related phenotypes and warrants further investigation as a potential therapeutic target in CKD.