OBJECTIVE: Free light chains (FLCs) are bi-products of normal immunoglobulin synthesis and are predominately removed from the circulation by the kidneys. This study assessed polyclonal FLCs as a novel biomarker of early diabetic kidney disease. RESEARCH DESIGN/ METHODS: Serum and urinary FLCs were assessed by the immunoassay Freelite, in white and South-Asian patients with type II diabetes recruited from the United Kingdom Asian Diabetes Study. RESULTS: The incidence of monoclonal proteins in this diabetic population was 1.9%. Type II diabetic patients had significantly raised concentrations of serum polyclonal FLCs before overt renal impairment developed (p < 0.001). Both kappa and lambda FLCs correlated with all tested markers of renal function; in particular cystatin-C: Spearman's coefficient (R) = 0.55 (p < 0.01) and R = 0.56 (p < 0.01), respectively. The South-Asian diabetic patients had higher serum polyclonal FLCs than Caucasian diabetic patients and this was independent of renal function. Urinary FLCs concentrations were raised in diabetic patients (p < 0.001). The majority (68%) of diabetic patients with normal urinary albumin:creatinine ratios (ACRs) had abnormal urinary FLC:creatinine ratios. Both kappa and lambda FLC concentrations correlated with urinary ACR: R = 0.32, p < 0.01 and R = 0.25, p < 0.01 respectively. CONCLUSIONS: Type II diabetic patients can have significantly raised concentrations of serum and urinary polyclonal FLCs before overt renal disease occurs. These novel findings provide the basis for future studies to assess whether polyclonal FLCs could provide a useful tool for early diagnosis of diabetic kidney disease.
OBJECTIVE: Free light chains (FLCs) are bi-products of normal immunoglobulin synthesis and are predominately removed from the circulation by the kidneys. This study assessed polyclonal FLCs as a novel biomarker of early diabetic kidney disease. RESEARCH DESIGN/ METHODS: Serum and urinary FLCs were assessed by the immunoassay Freelite, in white and South-Asian patients with type II diabetes recruited from the United Kingdom Asian Diabetes Study. RESULTS: The incidence of monoclonal proteins in this diabetic population was 1.9%. Type II diabeticpatients had significantly raised concentrations of serum polyclonal FLCs before overt renal impairment developed (p < 0.001). Both kappa and lambda FLCs correlated with all tested markers of renal function; in particular cystatin-C: Spearman's coefficient (R) = 0.55 (p < 0.01) and R = 0.56 (p < 0.01), respectively. The South-Asian diabeticpatients had higher serum polyclonal FLCs than Caucasian diabeticpatients and this was independent of renal function. Urinary FLCs concentrations were raised in diabeticpatients (p < 0.001). The majority (68%) of diabeticpatients with normal urinary albumin:creatinine ratios (ACRs) had abnormal urinary FLC:creatinine ratios. Both kappa and lambda FLC concentrations correlated with urinary ACR: R = 0.32, p < 0.01 and R = 0.25, p < 0.01 respectively. CONCLUSIONS:Type II diabeticpatients can have significantly raised concentrations of serum and urinary polyclonal FLCs before overt renal disease occurs. These novel findings provide the basis for future studies to assess whether polyclonal FLCs could provide a useful tool for early diagnosis of diabetic kidney disease.
Authors: Colin A Hutchison; Joan Bladé; Paul Cockwell; Mark Cook; Mark Drayson; Jean-Paul Fermand; Efstathios Kastritis; Robert Kyle; Nelson Leung; Sonia Pasquali; Christopher Winearls Journal: Nat Rev Nephrol Date: 2012-02-21 Impact factor: 28.314