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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
Authors:Simon DS Fraser  Anthony Fenton  Scott Harris  Adam Shardlow  Sophie Liabeuf  Ziad A Massy  Anne Burmeister  Colin A Hutchison  Martin Landray  Jonathan Emberson  Phil Kalra  James P Ritchie  Paul Cockwell  Maarten W Taal
Institution:1. Academic Unit of Primary Care and Population Science, Faculty of Medicine, University of Southampton, Southampton, United Kingdom;2. Department of Renal Medicine, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom;3. Centre for Kidney Research and Innovation, Division of Medical Sciences and Graduate Entry Medicine, School of Medicine, University of Nottingham, Royal Derby Hospital, Derby, United Kingdom;4. Clinical Research Centre and INSERM U1018, Amiens University Hospital, Amiens, France;5. The Binding Site Group Ltd, Birmingham, United Kingdom;6. Hawke''s Bay District Health Board, Hastings, New Zealand;7. Nuffield Department of Population Health, Oxford, United Kingdom;8. Department of Renal Medicine, Salford Royal Hospital, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom
Abstract:

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.
Keywords: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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