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The association between polyclonal combined serum free light chain concentration and mortality in individuals with early chronic kidney disease

The association between polyclonal combined serum free light chain concentration and mortality in individuals with early chronic kidney disease
The association between polyclonal combined serum free light chain concentration and mortality in individuals with early chronic kidney disease
A major component of increased mortality risk in people with chronic kidney disease (CKD) is associated with non-traditional cardiovascular risk factors including markers of inflammation. We studied whether a novel marker of systemic inflammation, elevated serum combined polyclonal immunoglobulin free light chains (cFLC), was an independent risk factor for increased all-cause mortality in people with CKD stage 3. In a prospective community based cohort study, 1695 participants with stage 3 CKD and no cases of monoclonal gammopathy had cFLC concentrations measured. cFLC levels were determined using the summation of Freelite kappa and lambda assays. All other bioclinical variables were collected at the time of sample collection. Kaplan-Meier plots and Cox proportional hazards analysis was used to assess the relationship between high cFLC levels (>43.3 mg/L) and mortality. There were 167 deaths (10%) after a median of 1375 days. cFLC levels at recruitment were higher in participants who died compared with those who were alive at the end of the study; median: 46.5 mg/L (IQR: 36.1-65.4 mg/L) and 35.4 mg/L (28.1-46.6 mg/L) respectively, P <0.001. Kaplan-Meier survival analysis demonstrated participants with cFLC >43.3 mg/L levels had an increased risk of mortality compared to people with normal cFLC levels (P <0.001). Elevated cFLC levels were independently associated with worse survival (Hazard ratio: 1.50; 95% confidence interval: 1.04-2.16; P=0.03). Other independent risk factors for worse survival were: older age, male gender, previous cardiovascular event, lower eGFR and higher high sensitivity C-reactive protein (hsCRP). To conclude, high cFLC levels predict increased mortality in people with stage 3 CKD, independent of established risk factors and other markers of inflammation.
1932-6203
1-15
Assi, L.K.
69b443a2-f39b-46bd-9e66-28efae7cae8f
McIntyre, N.
bfa1f732-3e6d-4880-b5d6-af787746cd64
Fraser, S.D.S.
135884b6-8737-4e8a-a98c-5d803ac7a2dc
Harris, S.
19ea097b-df15-4f0f-be19-8ac42c190028
Hutchison, C.
e9715326-6c28-4372-b413-e32fc3df15e5
McIntyre, C.W.
a6ecfaca-7548-44f3-9349-958764314409
Cockwell, P.
68f6888c-cee0-4f09-a5e7-f43697190d99
Taal, M.W.
93cf9569-6e4e-4de5-9a6f-b30d7c41a28b
Assi, L.K.
69b443a2-f39b-46bd-9e66-28efae7cae8f
McIntyre, N.
bfa1f732-3e6d-4880-b5d6-af787746cd64
Fraser, S.D.S.
135884b6-8737-4e8a-a98c-5d803ac7a2dc
Harris, S.
19ea097b-df15-4f0f-be19-8ac42c190028
Hutchison, C.
e9715326-6c28-4372-b413-e32fc3df15e5
McIntyre, C.W.
a6ecfaca-7548-44f3-9349-958764314409
Cockwell, P.
68f6888c-cee0-4f09-a5e7-f43697190d99
Taal, M.W.
93cf9569-6e4e-4de5-9a6f-b30d7c41a28b

Assi, L.K., McIntyre, N., Fraser, S.D.S., Harris, S., Hutchison, C., McIntyre, C.W., Cockwell, P. and Taal, M.W. (2015) The association between polyclonal combined serum free light chain concentration and mortality in individuals with early chronic kidney disease. PLoS ONE, 10 (7), 1-15. (doi:10.1371/journal.pone.0129980). (PMID:26132658)

Record type: Article

Abstract

A major component of increased mortality risk in people with chronic kidney disease (CKD) is associated with non-traditional cardiovascular risk factors including markers of inflammation. We studied whether a novel marker of systemic inflammation, elevated serum combined polyclonal immunoglobulin free light chains (cFLC), was an independent risk factor for increased all-cause mortality in people with CKD stage 3. In a prospective community based cohort study, 1695 participants with stage 3 CKD and no cases of monoclonal gammopathy had cFLC concentrations measured. cFLC levels were determined using the summation of Freelite kappa and lambda assays. All other bioclinical variables were collected at the time of sample collection. Kaplan-Meier plots and Cox proportional hazards analysis was used to assess the relationship between high cFLC levels (>43.3 mg/L) and mortality. There were 167 deaths (10%) after a median of 1375 days. cFLC levels at recruitment were higher in participants who died compared with those who were alive at the end of the study; median: 46.5 mg/L (IQR: 36.1-65.4 mg/L) and 35.4 mg/L (28.1-46.6 mg/L) respectively, P <0.001. Kaplan-Meier survival analysis demonstrated participants with cFLC >43.3 mg/L levels had an increased risk of mortality compared to people with normal cFLC levels (P <0.001). Elevated cFLC levels were independently associated with worse survival (Hazard ratio: 1.50; 95% confidence interval: 1.04-2.16; P=0.03). Other independent risk factors for worse survival were: older age, male gender, previous cardiovascular event, lower eGFR and higher high sensitivity C-reactive protein (hsCRP). To conclude, high cFLC levels predict increased mortality in people with stage 3 CKD, independent of established risk factors and other markers of inflammation.

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Accepted/In Press date: 13 May 2015
Published date: 1 July 2015
Organisations: Primary Care & Population Sciences

Identifiers

Local EPrints ID: 378262
URI: https://eprints.soton.ac.uk/id/eprint/378262
ISSN: 1932-6203
PURE UUID: 58318f1e-2aad-4ae6-b50f-c771b9569f6e
ORCID for S.D.S. Fraser: ORCID iD orcid.org/0000-0002-4172-4406

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Date deposited: 22 Jun 2015 14:59
Last modified: 20 Jul 2019 00:49

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Contributors

Author: L.K. Assi
Author: N. McIntyre
Author: S.D.S. Fraser ORCID iD
Author: S. Harris
Author: C. Hutchison
Author: C.W. McIntyre
Author: P. Cockwell
Author: M.W. Taal

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