Simon D S Fraser1, Anthony Fenton2, Scott Harris3, Adam Shardlow4, Sophie Liabeuf5, Ziad A Massy5, Anne Burmeister6, Colin A Hutchison7, Martin Landray8, Jonathan Emberson8, Phil A Kalra9, James P Ritchie9, Paul Cockwell2, Maarten W Taal4. 1. Academic Unit of Primary Care and Population Science, Faculty of Medicine, University of Southampton, Southampton, United Kingdom. Electronic address: s.fraser@soton.ac.uk. 2. Department of Renal Medicine, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom. 3. Academic Unit of Primary Care and Population Science, Faculty of Medicine, University of Southampton, Southampton, United Kingdom. 4. 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. 5. Clinical Research Centre and INSERM U1018, Amiens University Hospital, Amiens, France. 6. The Binding Site Group Ltd, Birmingham, United Kingdom. 7. Hawke's Bay District Health Board, Hastings, New Zealand. 8. Nuffield Department of Population Health, Oxford, United Kingdom. 9. 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.
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.
Authors: Daniel E Weiner; Luke Falzon; Line Skoufos; Angelito Bernardo; Werner Beck; Mengqi Xiao; Ha Tran Journal: Clin J Am Soc Nephrol Date: 2020-08-25 Impact factor: 8.237