A17(T)
COMBINED SERUM FREE LIGHT CHAIN LEVELS IN PATIENTS WITH CHRONIC
KIDNEY DISEASE STAGE 3
Assi, L¹, McIntyre, N², Hutchison, C³, Stringer, S³, Hughes, R¹, Fluck, R², McIntyre, C²,
Cockwell, P³, Taal, M²
¹The Binding Site Group Ltd, ²Royal Derby Hospital, ³Renal Institute of Birmingham
INTRODUCTION AND AIMS: Monoclonal immunoglobulin serum free light chains (sFLCs) are
elevated in many B-cell dyscrasias, including multiple myeloma, typically producing an abnormal κ/λ
sFLC ratio. Polyclonal sFLCs are also elevated in patients with kidney dysfunction. Increased
concentrations of κ and λ sFLCs can result from reduced clearance by the kidneys or increased
polyclonal production by plasma cells. Furthermore, there is evolving evidence that combined sFLCs
may be a strong independent risk factor for renal progression and survival in patients with CKD. The
aim of this study was to investigate the levels of sFLCs in patients with CKD stage 3, in a primary
care setting.
METHOD: 1741 patients with CKD stage 3 were recruited from Primary Care Practices. A detailed
medical history was obtained and each participant underwent clinical assessment as well as urine and
serum biochemistry tests. sFLCS were measured using the serum Freelite™ assay (Binding Site
Group Ltd) and turbidometric high sensitivity C-Reactive Protein (HSCRP) (Roche) measurements
were determined. Free κ and λ values were summated to give a combined sFLC value and κ/λ ratios
were calculated. sFLC values were compared against established normal ranges (κ: median 7.3mg/L,
range 3.3-19.4mg/L, λ: median 12.7mg/L, range 5.71-26.3mg/L, ratio: 0.26-1.65 and the renal
reference range: 0.37-3.1).
RESULTS: Subjects were predominantly white (98%) and female (60%), with an average age of 73
years. 17% had diabetes. The median estimated GFR (eGFR) was 53mL/min/1.73m2. At baseline,
both the median sFLC 19mg/L (4-181mg/L) and sFLC 17mg/L (2-74mg/L) concentrations were
elevated; combined sFLCs (>50mg/L) were elevated in 383/1741 (23%) patients. 30/1741 (1.7%)
patients had an abnormal
ratio as determined using the renal reference range, suggesting the
presence of a monoclonal gammopathy, and were excluded from further analysis. Correlation
analysis was performed between combined sFLC levels and various risk markers associated with
CKD (see Table). Multivariable linear regression analysis identified factors including eGFR, log urine
ACR, log HSCRP, serum albumin, haemoglobin, uric acid and cholesterol as independent
determinants of sFLC levels.
Correlation variables
Spearman R
P value
sFLCS vs age
sFLCs vs serum albumin
sFLCs vs eGFR
sFLCs vs HSCRP
sFLCs vs haemoglobin
sFLCs vs bicarbonate
sFLCs vs cholesterol
sFLCS vs uric acid
sFLCs vs pulsewave velocity
sFLCs vs urine ACR
sFLCs vs systolic blood pressure
sFLCs vs diastolic blood pressure
0.255
-0.27
-0.491
0.195
-0.22
-0.137
-0.247
0.322
0.112
0.322
0.053
-0.134
0.001
0.001
0.001
0.001
0.001
0.001
0.001
0.001
0.001
0.001
0.028
0.001
CONCLUSIONS:
concentrations more than twice the levels observed in healthy controls. The moderate association of
combined sFLCS with eGFR indicates that both kidney dysfunction and increased production
contribute to the elevated levels. sFLC levels correlated with several other risk factors associated with
CKD progression and survival. Long term follow-up will further elucidate these associations.