The interaction between fluid status and angiopoietin-2 in adverse renal outcomes of chronic kidney disease.
BACKGROUND
Fluid overload is not only the characteristic but also an important complication in chronic kidney disease (CKD) patients. Angiopoietin-2 (Angpt2) disturbs endothelium and vessel permeability, which may induce fluid overload. The aim of this study is to examine the interaction between fluid status and Angpt2 in adverse renal outcomes of CKD.


METHODS
This cohort study enrolled 290 patients with CKD stages 3-5 from January 2011 to December 2011 and followed up until December 2015. Fluid status was presented as overhydration (OH) value measured by body composition monitor, while OH>1.1L was defined as fluid overload. Renal outcomes were defined as commencing dialysis and rapid renal function decline (the slope of estimated glomerular filtration rate < -5 ml/min/1.73 m2/y).


RESULTS
During a mean follow-up of 38.6±18.3 months, 125 (43.1%) patients progressed to commencing dialysis and 99(34.7%) patients presented rapid renal function decline. All patients were stratified by OH of 1.1L and the median of circulating Angpt2. These patients with both OH>1.1L and high circulating Angpt2 were more likely to reach commencing dialysis compared to other groups. The risks for commencing dialysis and rapid renal function decline were significantly higher in patients with OH>1.1L and high circulating Angpt2 level compared to those with OH≦1.1L and low circulating Angpt2 (2.14, 1.21-3.78, P = 0.009; 4.96, 1.45-16.97, P = 0.01). There was a significant interaction between OH level and circulating Angpt2 in entering dialysis (P-interaction = 0.02).


CONCLUSIONS
Fluid overload and Angpt2 might have a synergistic effect on adverse renal outcomes in CKD patients.
Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Yi-Chun
http://orcid.org/0000-0003-4923-3342
YC
Tsai
Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Faculty of Renal Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Yi-Wen
YW
Chiu
Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Faculty of Renal Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Hung-Tien
HT
Kuo
Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Faculty of Renal Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Jia-Jung
JJ
Lee
Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Su-Chu
SC
Lee
Department of Nursing, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Tzu-Hui
TH
Chen
Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Faculty of Renal Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Ming-Yen
MY
Lin
Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Faculty of Renal Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Shang-Jyh
SJ
Hwang
Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Faculty of Renal Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Mei-Chuan
MC
Kuo
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Taiwan, Kaohsiung, Taiwan.
Ya-Ling
YL
Hsu
Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Faculty of Renal Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Hung-Chun
HC
Chen
D000368:Aged; D042702:Angiopoietin-2 / Q000097:blood* / Q000502:physiology; D003404:Creatinine / Q000097:blood; D018450:Disease Progression; D045604:Extracellular Fluid; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000503:physiopathology*; D014882:Water-Electrolyte Balance / Q000502:physiology*
C586513:ANGPT2 protein, human; D042702:Angiopoietin-2; D003404:Creatinine