Combined serum free light chain levels in patients with chronic kidney disease stage 3

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	0.255	0.001
sFLCs vs serum albumin	-0.27	0.001
sFLCs vs eGFR	-0.491	0.001
sFLCs vs HSCRP	0.195	0.001
sFLCs vs haemoglobin	-0.22	0.001
sFLCs vs bicarbonate	-0.137	0.001
sFLCs vs cholesterol	-0.247	0.001
sFLCS vs uric acid	0.322	0.001
sFLCs vs pulsewave velocity	0.112	0.001
sFLCs vs urine ACR	0.322	0.001
sFLCs vs systolic blood pressure	0.053	0.028
sFLCs vs diastolic blood pressure	-0.134	0.001

Conclusions: sFLCS are polyclonally elevated in patients with CKD stage 3 with free  chain 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.