title: The Association between Polyclonal Combined Serum Free Light Chain Concentration and Mortality in Individuals with Early Chronic Kidney Disease.
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.
authors.affiliation: The Binding Site Group Ltd, 8 Calthorpe Road, Edgbaston, Birmingham, United Kingdom.
authors.forename: Lakhvir K
authors.initials: LK
authors.lastname: Assi
authors.affiliation: Division of Medical Sciences and Graduate-Entry Medicine, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Natasha
authors.initials: N
authors.lastname: McIntyre
authors.affiliation: Academic Unit of Primary Care and Population Sciences, University of Southampton, Southampton, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: Fraser
authors.affiliation: Academic Unit of Primary Care and Population Sciences, University of Southampton, Southampton, United Kingdom.
authors.forename: Scott
authors.initials: S
authors.lastname: Harris
authors.affiliation: Hawke's Bay District Health Board, Hawke's Bay, New Zealand.
authors.forename: Colin A
authors.initials: CA
authors.lastname: Hutchison
authors.affiliation: Division of Medical Sciences and Graduate-Entry Medicine, University of Nottingham, Nottingham, United Kingdom; Renal Unit, Royal Derby Hospital, Derby, United Kingdom.
authors.forename: Chris W
authors.initials: CW
authors.lastname: McIntyre
authors.affiliation: Department of Renal Medicine, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom; Division of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Cockwell
authors.affiliation: Division of Medical Sciences and Graduate-Entry Medicine, University of Nottingham, Nottingham, United Kingdom; Renal Unit, Royal Derby Hospital, Derby, United Kingdom.
authors.forename: Maarten W
authors.initials: MW
authors.lastname: Taal
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000097:blood*; D007146:Immunoglobulin lambda-Chains / Q000097:blood*; D008297:Male; D051436:Renal Insufficiency, Chronic / Q000097:blood*
chemical_list: D015415:Biomarkers; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains