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The Association between Polyclonal Combined Serum Free Light Chain Concentration and Mortality in Individuals with Early Chronic Kidney Disease.

Assi LK, McIntyre N, Fraser S, Harris S, Hutchison CA, McIntyre CW, Cockwell P, Taal MW - PLoS ONE (2015)

Bottom Line: 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).To conclude, high cFLC levels predict increased mortality in people with stage 3 CKD, independent of established risk factors and other markers of inflammation.

View Article: PubMed Central - PubMed

Affiliation: The Binding Site Group Ltd, 8 Calthorpe Road, Edgbaston, Birmingham, United Kingdom.

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.

No MeSH data available.


Related in: MedlinePlus

Serum FLC concentration in people with stage 3 chronic kidney disease versus normal controls.A) κfree light chains (FLC), B) λFLC and C) Combined free light chains (cFLC) levels were elevated in people with chronic kidney disease (CKD) (circles) versus published normal control individuals [21]. D) The FLC κ/λ ratio was also significantly higher in people with CKD compared to the healthy control population. Median and ranges are indicated (black bars).
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pone.0129980.g002: Serum FLC concentration in people with stage 3 chronic kidney disease versus normal controls.A) κfree light chains (FLC), B) λFLC and C) Combined free light chains (cFLC) levels were elevated in people with chronic kidney disease (CKD) (circles) versus published normal control individuals [21]. D) The FLC κ/λ ratio was also significantly higher in people with CKD compared to the healthy control population. Median and ranges are indicated (black bars).

Mentions: The median serum κFLC concentration was 19.2 mg/L (IQR: 14.4–25.5 mg/L) and serum λFLC concentration was 17.3 mg/L (IQR: 13.5–22.7 mg/L) (Table 2); these were significantly elevated compared to previously reported FLC values in a normal healthy control population [21, 23] (κFLC median 7.3 mg/L; λFLC median 12.4 mg/L, P <0.001) (Fig 2A and 2B). The median cFLC concentration for the CKD population was 36.3 mg/L (IQR: 28.6–47.9 mg/L) (Table 2 and Fig 2C); median κ/λFLC ratio was 1.1 (IQR: 0.9–1.3), which was significantly higher than controls, P <0.001 (Fig 2D). Males had significantly elevated cFLC concentrations compared to females: 41.95 mg/L (IQR:32.86–54.78 mg/L) vs 33.31 mg/L (IQR:26.85–44.32 mg/L) respectively P <0.001 (Fig 3). cFLC levels were elevated (>43.3 mg/L) in 584 (34%) patients. cFLC correlated inversely with eGFR (rho = -0.49, P <0.0001; Fig 4, Table 3). Weak but significant correlations were observed between cFLC and albumin (rho = -0.28), hsCRP (rho = 0.19), Hb (rho = -0.22), cholesterol (rho = -0.25), HDL cholesterol (rho = -0.23), PWV (rho = 0.11), uACR (rho = 0.32), DBP (rho = -0.14) and WHR (rho = 0.27) (P <0.01 for all). There was no significant correlation between cFLC and BMI, calcium or phosphate levels.


The Association between Polyclonal Combined Serum Free Light Chain Concentration and Mortality in Individuals with Early Chronic Kidney Disease.

Assi LK, McIntyre N, Fraser S, Harris S, Hutchison CA, McIntyre CW, Cockwell P, Taal MW - PLoS ONE (2015)

Serum FLC concentration in people with stage 3 chronic kidney disease versus normal controls.A) κfree light chains (FLC), B) λFLC and C) Combined free light chains (cFLC) levels were elevated in people with chronic kidney disease (CKD) (circles) versus published normal control individuals [21]. D) The FLC κ/λ ratio was also significantly higher in people with CKD compared to the healthy control population. Median and ranges are indicated (black bars).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4489104&req=5

pone.0129980.g002: Serum FLC concentration in people with stage 3 chronic kidney disease versus normal controls.A) κfree light chains (FLC), B) λFLC and C) Combined free light chains (cFLC) levels were elevated in people with chronic kidney disease (CKD) (circles) versus published normal control individuals [21]. D) The FLC κ/λ ratio was also significantly higher in people with CKD compared to the healthy control population. Median and ranges are indicated (black bars).
Mentions: The median serum κFLC concentration was 19.2 mg/L (IQR: 14.4–25.5 mg/L) and serum λFLC concentration was 17.3 mg/L (IQR: 13.5–22.7 mg/L) (Table 2); these were significantly elevated compared to previously reported FLC values in a normal healthy control population [21, 23] (κFLC median 7.3 mg/L; λFLC median 12.4 mg/L, P <0.001) (Fig 2A and 2B). The median cFLC concentration for the CKD population was 36.3 mg/L (IQR: 28.6–47.9 mg/L) (Table 2 and Fig 2C); median κ/λFLC ratio was 1.1 (IQR: 0.9–1.3), which was significantly higher than controls, P <0.001 (Fig 2D). Males had significantly elevated cFLC concentrations compared to females: 41.95 mg/L (IQR:32.86–54.78 mg/L) vs 33.31 mg/L (IQR:26.85–44.32 mg/L) respectively P <0.001 (Fig 3). cFLC levels were elevated (>43.3 mg/L) in 584 (34%) patients. cFLC correlated inversely with eGFR (rho = -0.49, P <0.0001; Fig 4, Table 3). Weak but significant correlations were observed between cFLC and albumin (rho = -0.28), hsCRP (rho = 0.19), Hb (rho = -0.22), cholesterol (rho = -0.25), HDL cholesterol (rho = -0.23), PWV (rho = 0.11), uACR (rho = 0.32), DBP (rho = -0.14) and WHR (rho = 0.27) (P <0.01 for all). There was no significant correlation between cFLC and BMI, calcium or phosphate levels.

Bottom Line: 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).To conclude, high cFLC levels predict increased mortality in people with stage 3 CKD, independent of established risk factors and other markers of inflammation.

View Article: PubMed Central - PubMed

Affiliation: The Binding Site Group Ltd, 8 Calthorpe Road, Edgbaston, Birmingham, United Kingdom.

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.

No MeSH data available.


Related in: MedlinePlus