Journal article
The role of albumin and the extracellular matrix on the pathophysiology of oedema formation in severe malnutrition
- Abstract:
- Background While fluid flows in a steady state from plasma, through interstitium, and into the lymph compartment, altered fluid distribution and oedema can result from abnormal Starling's forces, increased endothelial permeability or impaired lymphatic drainage. The mechanism of oedema formation, especially the primary role of hypoalbuminaemia, remains controversial. Here, we explored the roles of albumin and albumin-independent mechanisms in oedema formation among children with severe malnutrition (SM). Methods We performed secondary analysis of data obtained from two independent clinical trials in Malawi and Kenya (NCT02246296 and NCT00934492). We then used an unconventional strategy of comparing children with kwashiorkor and marasmus by matching (discovery cohort, n = 144) and normalising (validation cohort, n = 98, 2 time points) for serum albumin. Untargeted proteomics was used in the discovery cohort to determine plausible albumin-independent mechanisms associated with oedema, which was validated using enzyme-linked immunosorbent assay and multiplex assays in the validation cohort. Findings We demonstrated that low serum albumin is necessary but not sufficient to develop oedema in SM. We further found that markers of extracellular matrix (ECM) degradation rather than markers of EG degradation distinguished oedematous and non-oedematous children with SM. Interpretation Our results show that oedema formation has both albumin-dependent and independent mechanisms. ECM integrity appears to have a greater role in oedema formation than EG shedding in SM.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 2.3MB, Terms of use)
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- Publisher copy:
- 10.1016/j.ebiom.2022.103991
Authors
- Publisher:
- Elsevier
- Journal:
- eBioMedicine More from this journal
- Volume:
- 79
- Article number:
- 103991
- Publication date:
- 2022-04-07
- Acceptance date:
- 2022-03-24
- DOI:
- EISSN:
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2352-3964
- Language:
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English
- Keywords:
- Pubs id:
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1249928
- Local pid:
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pubs:1249928
- Deposit date:
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2022-04-11
- ARK identifier:
Terms of use
- Copyright holder:
- Gonzales et al.
- Copyright date:
- 2022
- Rights statement:
- Copyright 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
- Licence:
- CC Attribution (CC BY)
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