The Association of Serum Free Light Chains With Mortality and Progression to End-Stage Renal Disease in Chronic Kidney Disease: Systematic Review and Individual Patient Data Meta-analysis.
Fraser SDS., Fenton A., Harris S., Shardlow A., Liabeuf S., Massy ZA., Burmeister A., Hutchison CA., Landray M., Emberson J., Kalra PA., Ritchie JP., Cockwell P., Taal MW.
OBJECTIVE: To clarify the associations between polyclonal serum free light chain (sFLC) levels and adverse outcomes in patients with chronic kidney disease (CKD) by conducting a systematic review and individual patient data meta-analyses. PATIENTS AND METHODS: On December 28, 2016, we searched 4 databases (MEDLINE, Embase, CINAHL, and PubMed) and conference proceedings for studies presenting independent analyses of associations between sFLC levels and mortality or progression to end-stage renal disease (ESRD) in patients with CKD. Study quality was assessed in 5 domains: sample selection, measurement, attrition, reporting, and funding. RESULTS: Five prospective cohort studies were included, judged moderate to good quality, involving 3912 participants in total. In multivariable meta-analyses, sFLC (kappa+lambda) levels were independently associated with mortality (5 studies, 3680 participants; hazard ratio [HR], 1.04 [95% CI, 1.03-1.06] per 10 mg/L increase in sFLC levels) and progression to ESRD (3 studies, 1848 participants; HR, 1.01 [95% CI, 1.00-1.03] per 10 mg/L increase in sFLC levels). The sFLC values above the upper limit of normal (43.3 mg/L) were independently associated with mortality (HR, 1.45 [95% CI, 1.14-1.85]) and ESRD (HR, 3.25 [95% CI, 1.32-7.99]). CONCLUSION: Higher levels of sFLCs are independently associated with higher risk of mortality and ESRD in patients with CKD. Future work is needed to explore the biological role of sFLCs in adverse outcomes in CKD, and their use in risk stratification.