Quantitative assessment of serum and urinary polyclonal free light chains in patients with chronic kidney disease

Abstract

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.

Figures

Figure 1.

Schematic of chronic kidney disease (CKD) populations assessed. N/A, not available.

Figure 2.

Serum free light chain (FLC) concentrations in patients with CKD. (A) Both κ ( ) and λ (□) FLC increased progressively with each CKD stage (both P < 0.0001). (B) Patients who required renal replacement therapy had serum FLC concentrations significantly higher than patients with stage 5 CKD (both P < 0.001). There were no significant differences in serum concentrations of FLC between the peritoneal dialysis (PD) and hemodialysis (HD) populations: κ, P < 0.09; λ, P < 0.5. Data presented as box plots with whiskers; solid lines denote median values.

Figure 3.

Serum FLC ratio in patients with CKD. (A) The FLC ratio increased progressively through stages 1 through 5 CKD: 0.85 (0.3 to 1.8), 0.86 (0.5 to 1.92), 1.04 (0.45 to 2.3), 1.16 (0.49 to 3), and 1.19 (0.6 to 2.9), respectively (P < 0.01). (B) The FLC ratio was also significantly raised in patients who received renal replacement therapy compared with that of the control population: 0.6 (0.26 to 1.65); PD 0.97 (0.32 to 2.35) and HD 1.2 (0.69 to 2.57). Data presented as box plots with whiskers; solid lines denote median values.

Figure 4.

Relationship of urinary FLC/creatinine ratios with CKD stages. Both κ/creatinine ratio (KCR; ) and λ/creatinine ratio (LCR; □) increased progressively through each CKD stage; 1, 2.3 (0.3 to 21) and 0.25 (0.03 to 8.7); 2, 2.3 (0.11 to 31) and 0.39 (0.02 to 10); 3, 7.2 (0.1 to 126) and 1.23 (0.01 to 70); 4, 17 (0.22 to 123) and 4.55 (0 to 36.8); and 5, 24 (4.2 to 121) and 6.1 (0.78 to 77), respectively (both P < 0.0001). Data presented as box plots with whiskers; solid lines denote median values.

Figure 5.

Percentage of patients with abnormal urinary FLC/creatinine ratios according to urinary albumin/creatinine ratio (ACR; A) and CKD stages (B). The percentage of patients with abnormal urinary FLC/creatinine ratios increased with increasing ACR (20 = 93%; P < 0.001) and through the CKD stages (1 through 5: 36, 50, 74, 89, and 100%, respectively; P < 0.001).