Comorbidity burden may explain adiponectin's paradox as a marker of increased mortality risk in hemodialysis patients

Despite experimental evidence of beneficial metabolic, antiatherosclerotic and antiinflammatory effects of the 30 kDa adipokine, adiponectin, maintenance hemodialysis (MHD) patients with high adiponectin blood levels have paradoxically high mortality rates. We aimed to examine the direction of the associations between adiponectin and all-cause and cardiovascular mortality as well as with markers of oxidative stress, inflammation and nutrition in MHD patients with varying degrees of comorbidities. A cohort of 261 MHD patients (mean age 68.6 ± 13.6 years, 38.7% women), grouped according to baseline comorbidity index (CI) and serum adiponectin levels, were followed prospectively for six years. High and low concentrations were established according to median CI and adiponectin levels and cross-classified. Across the four CI-adiponectin categories, the group with low comorbidities and high adiponectin exhibited the best outcomes. Conversely, the high comorbidity group with high adiponectin levels had the lowest survival rate in both all-cause mortality (log rankχ² = 23.74, p < 0.001) and cardiovascular mortality (log rankχ² = 34.16, p < 0.001). Further data adjustment for case-mix covariates including fat mass index did not substantially affect these results. In conclusion, the direction of adiponectin's prognostic associations in MHD patients is inverse in those with few comorbidities and direct in those with many comorbidities.