Impaired leukocytes autophagy in chronic kidney disease patients.
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.


CONCLUSIONS
These data suggest that CKD patients have impaired autophagy activation, which cannot be reversed with hemodialysis and is closely related to their cardiac abnormalities.
Department of Cardiology, Chang Gung University College of Medicine, Taoyuan, ROC.
Wei-Ting
WT
Chen
Department of Cardiology, Chang Gung University College of Medicine, Taoyuan, ROC.
Kuo-Chun
KC
Hung
Department of Cardiology, Chang Gung University College of Medicine, Taoyuan, ROC.
Ming-Shien
MS
Wen
Kidney Research Center, Department of Nephrology, Chang Gung University College of Medicine, Taoyuan, ROC.
Po-Yaur
PY
Hsu
Department of Cardiology, Chang Gung University College of Medicine, Taoyuan, ROC.
Tien-Hsing
TH
Chen
Institute of Biotechnology and Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan, ROC.
Horng-Dar
HD
Wang
Kidney Research Center, Department of Nephrology, Chang Gung University College of Medicine, Taoyuan, ROC.
Ji-Tseng
JT
Fang
Division of Infectious Diseases, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, ROC.
Shian-Sen
SS
Shie
Department of Cardiology, Chang Gung University College of Medicine, Taoyuan, ROC.
Chao-Yung
CY
Wang
Autophagy; Cardiovascular diseases; Light chain 3; Renal failure