P148
POLYCLONAL IMMUNOGLOBULIN FREE LIGHT CHAINS PREDICT PATIENT
SURVIVAL AND RENAL DECLINE IN CHRONIC KIDNEY DISEASE
Hutchison, C, Mead, G, Harding, S, Basnayake, K, Stringer, S, Ferro, C, Bradwell, A,
Cockwell, P
Renal Institute of Birmingham, Queen Elizabeth Hospital, Birmingham and Department of Infection and Immunity, University of Birmingham
PROBLEMS: Chronic kidney disease (CKD) is associated with a greatly increased morbidity and mortality. The currently available tools for identifying CKD patients at ‘high-risk’ of future events are inadequate. Polyclonal immunoglobulin free light chains (FLC) combine the established risk factors of renal function and inflammation and may represent a sensitive biomarker for this population.
PURPOSES: To evaluate serum polyclonal immunoglobulin FLCs as an independent marker of patient survival and progressive disease in CKD.
DESIGN: A prospective cohort of 1394 patients with CKD was recruited from our institution.
Baseline assessment included patient demographics, renal diagnosis, medications, renal function by eGFR, and CKD stage. Patients were followed up for survival and progression of CKD.
FINDINGS: The population was predominately male (54%) with a median age of 58 (range
18-92). The median eGFR at assessment was 44 ml/min/1.73m2 (0-145), the median urinary
ACR was 9.4 mg/mmol (0-1318). Twenty-four patients had evidence of a monoclonal protein and were therefore excluded from further analysis. During a median follow-up of 32 months (0-
64) there were 184 deaths. By Cox-regression analysis, age, gender, eGFR and total serum FLC concentration were survival determinants (all: P<0.001). In multi-variant analysis only age, gender and total FLCs independently predicted survival, HR (95% CI): 1.76 (1.57-1.99),
P<0.0001; 1.39 (1.01-1.91), P=0.04; 2.25 (1.81-2.8), P<0.001, respectively. Total FLCs predicted patients at risk of cardiovascular, infectious and cancer deaths. For renal function, Age
(P<0.001), total FLC (P=0.02) were independent predictors of a decline in renal function with time (by delta eGFR).
CONCLUSION: In this prospective study total serum concentrations of polyclonal FLCs were an independent marker of death and deterioration of renal function. These findings now need to be validated in other populations and possible interventions explored.
RELEVANCE: The tools for identifying patients with renal diseases who are at high risk of adverse events remain inadequate. The measurement of serum FLCs has great promise as a novel biomarker for identifying patients with CKD at high risk of poor clinical outcomes.