Dataset Information

Serum free light chains and the risk of ESRD and death in CKD.

ABSTRACT:

Background 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).

Results

After 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).

Conclusions

Associations 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.

SUBMITTER: Haynes R

PROVIDER: S-EPMC3255360 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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Publications

Serum free light chains and the risk of ESRD and death in CKD.

Haynes Richard R Hutchison Colin A CA Emberson Jonathan J Dasgupta Tanaji T Wheeler David C DC Townend John N JN Landray Martin J MJ Cockwell Paul P

Clinical journal of the American Society of Nephrology : CJASN 20111027 12

<h4>Background and objectives</h4>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).<h4>Design, setting, participants, & measurements</h4>Three hundred sixty-four patients selecte ...[more]

PMID: 22034503

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Project description:Background and objectivesHigh levels of serum polyclonal combined Ig free light chains are associated with inflammation and decreased excretory kidney function, and they are an independent risk factor for mortality. Whether combined Ig free light chain predicted mortality and progression to ESRD in a stages 3-5 CKD cohort was assessed.Design, setting, participants, & measurementsThis was a prospective cohort study of 872 patients with stages 3-5 CKD (nondialysis) recruited into the Chronic Renal Insufficiency Standards Implementation Study. Patients were recruited to the Chronic Renal Insufficiency Standards Implementation Study in an unselected manner from secondary care nephrology clinics between 2004 and 2010. Combined Ig free light chain was measured at recruitment and analyzed by quartiles. The cohort was followed up for a median of 41.4 months (interquartile range =28.3-68.0 months). Cox regression analysis was undertaken to determine the variables associated with mortality and progression to ESRD.ResultsCombined Ig free light chain quartiles were <49.4, 49.4-68.8, 68.9-100.7, and >100.7 mg/L. An independent association with death and progression to ESRD was associated with the third and fourth combined Ig free light chain quartiles (quartile 3: death: hazard ratio, 1.49; 95% confidence interval, 1.02 to 2.18; P=0.04; ESRD: hazard ratio, 1.72; 95% confidence interval, 1.0 to 2.97; P=0.05; quartile 4: death: hazard ratio, 1.99; 95% confidence interval, 1.34 to 2.93; P<0.001; ESRD: hazard ratio, 3.73; 95% confidence interval, 2.1 to 6.3; P<0.001). The other independent risk factors were (1) preexisting cardiovascular disease, age >65 years old, and eGFR=15-30 ml/min per 1.73 m(2) for death and (2) age ?65 years old, eGFR<30 ml/min per 1.73 m(2), urinary protein-to-creatinine ratio >30 mg/mmol, and serum phosphate level >4.65 mg/dl for progression to ESRD.ConclusionsAn elevated serum combined Ig free light chain level is an independent risk factor for mortality and progression to ESRD in patients with stages 3-5 CKD managed in secondary care.

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Project description:BACKGROUND AND OBJECTIVES: Rising prevalence of CKD requires active involvement of general practitioners to limit ESRD and mortality risk. However, the outcomes of patients with CKD exclusively managed by general practitioners are ill defined. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We prospectively evaluated 30,326 adult patients with nondialysis CKD stages 1-5 who had never received consultation in tertiary nephrology care recruited from 700 general practitioner offices in Italy during 2002 and 2003. CKD stages were classified as stages 1 and 2 (GFR ? 60 ml/min per 1.73 m(2) and either albuminuria or an International Classification of Diseases, Ninth Revision, Clinical Modification code for kidney disease), stage 3a (GFR=59-45), stage 3b (GFR=44-30), stage 4 (GFR=29-15), and stage 5 (GFR<15). Primary outcome was the risk of ESRD (dialysis or transplantation) or all-cause death. RESULTS: Overall 64% of patients were in stage 3a, and 4.5% of patients were in stages 3b-5. Patients with stages 1 and 2 were younger, were predominantly men, more frequently had diabetes, and had lower prevalence of previous cardiovascular disease than patients with stages 3a-5. Hypertension was frequent in all CKD stages (80%-94%), whereas there was a lower prevalence of dyslipidemia, albuminuria, and obesity associated with more advanced CKD. During the follow-up (median=7.2 years; interquartile range=4.7-7.7), 6592 patients died and 295 started ESRD. Compared with stages 1 and 2 (reference), mortality risk (hazard ratio, 95% confidence interval) was higher in stages 3b-5 (1.66, 1.49-1.86, 2.75, 2.41-3.13 and 2.54, 2.01-3.22, respectively) but not stage 3a (1.11, 0.99-1.23). Similarly, ESRD risk (hazard ratio, 95% confidence interval) was not higher at stage 3a (1.44, 0.79-2.64) but was greater in stages 3b-5 (11.0, 6.3-19.5, 91.2, 53.2-156.2 and, 122.8, 67.9-222.0, respectively). Among modifiable risk factors, anemia and albuminuria significantly predicted either outcome, whereas hypertension only predicted mortality. CONCLUSIONS: In patients with CKD not referred to nephrology, risks of ESRD and mortality were higher in those with CKD stages 3b-5.

Dataset Information

Serum free light chains and the risk of ESRD and death in CKD.

Background and objectives

Design, setting, participants, & measurements

Results

Conclusions

Publications

Serum free light chains and the risk of ESRD and death in CKD.

Similar Datasets

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