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Quantitative Assessment of Serum and Urinary Polyclonal Free Light Chains in Patients with Chronic Kidney Disease

Colin A. Hutchison^*,, Stephen Harding, Pete Hewins^*, Graham P. Mead^,||, John Townsend, Arthur R. Bradwell^,||, and Paul Cockwell^*,

Departments of ^* Renal Medicine and Cardiology, Queen Elizabeth Hospital, QEMC, The Binding Site Ltd., and Divisions of Medical Sciences and ^|| Immunity and Infection, Medical School, University of Birmingham, Birmingham, United Kingdom

Correspondence: Dr. Colin A. Hutchison, Renal Unit, University Hospital Birmingham, Birmingham, B152TH, UK. Phone: +44-7723917870; Fax: +44-1214306482; E-mail: cah692{at}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 and FLC concentrations increased progressively with CKD stage (both P < 0.001) and strongly correlated with markers of renal function, including cystatin-C (: R = 0.8, P < 0.01; and : R = 0.79, P < 0.01). Urinary FLC concentrations varied significantly between disease groups (: P < 0.001; : 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 (: R = 0.63; : R = 0.65; both P < 0.001) and urinary albumin creatinine ratio (: R = 0.58; : 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.