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Quantitative assessment of serum and urinary polyclonal free light chains in patients with chronic kidney disease
Colin A Hutchison1, Stephen Harding, Pete Hewins
1Renal Unit, University Hospital Birmingham, Birmingham, UK. cah692@bham.ac.uk
Background And Objectives:
Monoclonal free light chains (FLC) frequently cause kidney disease in patients with plasma cell dyscrasias. Polyclonal FLC, however, have not been assessed in patients with chronic kidney disease (CKD) yet could potentially play an important pathologic role. This study describes for the first time polyclonal FLC in patients with CKD.
Design, Setting, Participants, & Measurements:
A sensitive, quantitative immunoassay was used to analyze serum and urinary polyclonal FLC in 688 patients with CKD of various causes.
Results:
Serum kappa and lambda FLC concentrations increased progressively with CKD stage (both P < 0.001) and strongly correlated with markers of renal function, including cystatin-C (kappa: R = 0.8, P < 0.01; and lambda: R = 0.79, P < 0.01). Urinary FLC concentrations varied significantly between disease groups (kappa: P < 0.001; lambda: P < 0.005) and also rose significantly with increasing CKD stage (both FLC P < 0.0001). Urinary FLC concentrations were positively correlated with their corresponding serum concentration (kappa: R = 0.63; lambda: R = 0.65; both P < 0.001) and urinary albumin creatinine ratio (kappa: R = 0.58; lambda: R = 0.65; both P < 0.001). The proportion of patients with abnormally high urinary FLC concentrations rose with both the CKD stage and the severity of albuminuria.
Conclusions:
This study demonstrates significant abnormalities of serum and urinary polyclonal FLC in patients with CKD. These data provide the basis for studies that assess the contribution of polyclonal FLC to progressive renal injury and systemic inflammation in patients with kidney disease.
Insights
This study reveals abnormal levels of polyclonal free light chains (FLC) in the blood and urine of patients with chronic kidney disease (CKD). These findings suggest FLC may contribute to kidney damage.
Area of Science:
- Nephrology
- Immunology
- Biochemistry
Background:
- Monoclonal free light chains (FLC) are known to cause kidney disease in plasma cell disorders.
- The role of polyclonal FLC in chronic kidney disease (CKD) has not been previously investigated.
- Polyclonal FLC may play a significant pathological role in CKD progression.
Purpose of the Study:
- To investigate and characterize polyclonal FLC levels in patients with CKD.
- To assess the relationship between polyclonal FLC and CKD severity.
- To explore the correlation of polyclonal FLC with renal function markers and albuminuria.
Main Methods:
- A sensitive, quantitative immunoassay was employed.
- Serum and urinary polyclonal FLC were analyzed.
- 688 patients with various causes of CKD were included.
Main Results:
- Serum and urinary polyclonal FLC concentrations increased with CKD stage.
- FLC levels strongly correlated with markers of renal function, including cystatin-C.
- Urinary FLC concentrations correlated with serum FLC, urinary albumin-to-creatinine ratio, and increased with albuminuria severity.
Conclusions:
- Significant abnormalities in serum and urinary polyclonal FLC were observed in CKD patients.
- These findings establish a basis for further research into the role of polyclonal FLC in renal injury.
- Polyclonal FLC may contribute to progressive kidney damage and systemic inflammation in kidney disease.
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