Serum Free Light Chains and the Risk of ESRD and Death in CKD

Abstract

SummaryBackground and objectives Associations between inflammation and ESRD and death in chronic kidney disease are well established. However, the potential role of the adaptive immune system is uncertain. We aimed to prospectively study the relevance of the adaptive immune system to ESRD and mortality by measuring monoclonal and polyclonal excesses of highly sensitive serum free light chains (sFLCs).Design, setting, participants, & measurements Three hundred sixty-four patients selected from a nephrology outpatient clinic had kappa and lambda sFLCs concentrations and serum immunofixation electrophoresis measured. Cox regression was used to assess the relevance of monoclonal and polyclonal excess of sFLCs to the incidence of ESRD and death (mean follow-up for death 6.0 years). ResultsAfter adjustment for baseline eGFR, there was no significant association between monoclonal excess of sFLCs and risk of ESRD or mortality. Baseline log and log concentrations were positively associated with ESRD risk, but these associations seemed to be due to correlations with eGFR (per 1 SD higher concentration: adjusted hazard ratio 1.05 [95% confidence interval 0.88 to 1.26] and 0.99 [0.83 to 1.19], respectively). For mortality, after adjustment for eGFR plus markers of cardiac damage, there was weak evidence of an association with , but not , sFLC concentration (fully adjusted hazard ratio 1.33 [95% confidence interval 1.05 to 1.67] per 1 SD higher concentration). ConclusionsAssociations between monoclonal and polyclonal excess of sFLCs and risk of ESRD are explained by the correlation between these measures and renal function. We found only weak evidence of an association between polyclonal excess of sFLC concentration and mortality.

Association of Serum Ig Free Light Chains with Mortality and ESRD among Patients with Nondialysis-Dependent CKD

“…This stronger association of FLC than CRP with clinical outcomes has also been shown in other studies that have used CRP and cFLC (14,15). We have recently shown that the kinetics of CRP and cFLC levels in disease states differ, with CRP levels more closely associated with acute inflammation and FLC associated with chronic inflammation (28).…”

“…In an analysis of the Chronic Renal Impairment in Birmingham Study data, there was a weak independent association with polyclonal lFLC in a multivariable model that included troponin and N-terminal pro brain natriuretic peptide (14). However, this cohort included patients with a higher degree of comorbidity and more advanced CKD (mean eGFR=21.9 ml/min per 1.73 m 2 ) compared with this study population.…”

“…Previous studies have reported variable associations between cFLC and nontraditional risk factors for poor outcomes in CKD, including CRP and phosphate (14,16). Figure 1.…”

“…They all show an association between elevated FLC and mortality (14)(15)(16). However, the predictive strength of this association has not been defined, and there have been no studies of the relationship between cFLC and risk of progression to ESRD as well as mortality in a secondary care cohort comprising patients with stages 3-5 predialysis CKD.…”

“…However, the predictive strength of this association has not been defined, and there have been no studies of the relationship between cFLC and risk of progression to ESRD as well as mortality in a secondary care cohort comprising patients with stages 3-5 predialysis CKD. The previous studies of cFLC in patients with moderate to advanced CKD represented relatively small patient numbers and a low prevalence of patients with diabetes (14,15). The largest and most recent study included patients with preserved renal function and did not consider progression of renal failure (16).…”