Impaired Leukocytes Autophagy in Chronic Kidney Disease Patients

Abstract

Background: Proteins and cytoplasmic organelles undergo degradation and recycling via autophagy; its role in patients with chronic kidney disease (CKD) is still unclear. We hypothesize that impaired kidney function causes autophagy activation failure. Methods: We included 60 patients with stage 5 CKD and 30 age- and sex-matched healthy subjects as controls. Patients with conditions that could affect autophagy were excluded. Leukocytes were isolated and analyzed from peripheral blood samples collected after overnight fasting and 2 h after breakfast. Results: Overnight fasting induced conversion of microtubule-associated protein-1 light chain 3 I to II (γLC3) and increased mRNA levels of the autophagy-related gene 5 (Atg5) and Beclin-1 in healthy subjects, which were nearly absent in CKD patients (p = 0.0001). Moreover, no significant difference in autophagy activation was observed between CKD patients with or without hemodialysis. Correlation studies showed that γLC3 was negatively associated with the left atrium size. Changes in Atg5 transcript levels were negatively associated with the left ventricular end-diastolic diameter, and changes in Beclin-1 transcript levels were negatively associated with the mitral inflow E- and A-wave sizes. Conclusion: These data suggest that CKD patients have impaired autophagy activation, which cannot be reversed with hemodialysis and is closely related to their cardiac abnormalities.