title: Volume overload and adverse outcomes in chronic kidney disease: clinical observational and animal studies.
abstract: BACKGROUND
  Volume overload is frequently encountered and is associated with cardiovascular risk factors in patients with chronic kidney disease (CKD). However, the relationship between volume overload and adverse outcomes in CKD is not fully understood.
  
  
  RESULTS
  A prospective cohort of 338 patients with stage 3 to 5 CKD was followed for a median of 2.1 years. The study participants were stratified by the presence or absence of volume overload, defined as an overhydration index assessed by bioimpedance spectroscopy exceeding 7%, the 90th percentile for the healthy population. The primary outcome was the composite of estimated glomerular filtration rate decline ≥50% or end-stage renal disease. The secondary outcome included a composite of morbidity and mortality from cardiovascular causes. Animal models were used to simulate fluid retention observed in human CKD. We found that patients with volume overload were at a higher risk of the primary and secondary end points in the adjusted Cox models. Furthermore, overhydration appears to be more important than hypertension in predicting an elevated risk. In rats subjected to unilateral nephrectomy and a high-salt diet, the extracellular water significantly increased. This fluid retention was associated with an increase in blood pressure, proteinuria, renal inflammation with macrophage infiltration and tumor necrosis factor-α overexpression, glomerular sclerosis, and cardiac fibrosis. Diuretic treatment with indapamide attenuated these changes, suggesting that fluid retention might play a role in the development of adverse outcomes.
  
  
  CONCLUSIONS
  Volume overload contributes to CKD progression and cardiovascular diseases. Further research is warranted to clarify whether the correction of volume overload would improve outcomes for CKD patients.
authors.affiliation: Division of Nephrology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan (S.C.H., K.L.K.) School of Medicine, Tzu Chi University, Hualien, Taiwan (S.C.H., K.L.K.).
authors.forename: Szu-Chun
authors.initials: SC
authors.lastname: Hung
authors.affiliation: Institute of Physiology, National Yang-Ming University, Taipei, Taiwan (Y.S.L., D.C.T.).
authors.forename: Yi-Shin
authors.initials: YS
authors.lastname: Lai
authors.affiliation: Division of Nephrology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan (S.C.H., K.L.K.) School of Medicine, Tzu Chi University, Hualien, Taiwan (S.C.H., K.L.K.).
authors.forename: Ko-Lin
authors.initials: KL
authors.lastname: Kuo
authors.affiliation: Institute of Physiology, National Yang-Ming University, Taipei, Taiwan (Y.S.L., D.C.T.) Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (D.C.T.).
authors.forename: Der-Cherng
authors.initials: DC
authors.lastname: Tarng
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001826:Body Fluids / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000503:physiopathology; D015897:Comorbidity; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000150:complications; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D051381:Rats; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000503:physiopathology; D012307:Risk Factors; D014882:Water-Electrolyte Balance / Q000502:physiology*; D014883:Water-Electrolyte Imbalance / Q000150:complications* / Q000503:physiopathology
keywords: bioimpedance; cardiovascular disease; chronic kidney disease; hypertension; overhydration; volume overload