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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



      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.


      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]).


      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.

      Abbreviations and Acronyms:

      CKD (chronic kidney disease), CVD (cardiovascular disease), DM (diabetes mellitus), eGFR (estimated glomerular filtration rate), ESRD (end-stage renal disease), HR (hazard ratio), MDRD (modification of diet in renal disease formula), hsCRP (high-sensitivity C-reactive protein), MGUS (monoclonal gammopathy of uncertain significance), NT-proBNP (N-terminal pro–B-type natriuretic peptide), PCR (protein to creatinine ratio), PWV (pulse wave velocity), RAAS (renin-angiotensin-aldosterone system), RRT (renal replacement therapy), SBP (systolic blood pressure), sFLC (serum free light chain), uACR (urine albumin to creatinine ratio)
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      • Correction
        Mayo Clinic ProceedingsVol. 92Issue 12
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          In the Original Article entitled, “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” published in the November 2017 issue of Mayo Clinic Proceedings (Mayo Clin Proc. 2017;92(11):1671-1681), the middle initial was not included for one of the authors. His name should be listed as Phil A. Kalra.
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