title: Association of Serum Ig Free Light Chains with Mortality and ESRD among Patients with Nondialysis-Dependent CKD.
abstract: OBJECTIVE
  High 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.
  
  
  METHODS
  This 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.
  
  
  RESULTS
  Combined 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.
  
  
  CONCLUSIONS
  An 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.
authors.affiliation: Department of Renal Medicine, Salford Royal National Health Service Foundation Trust, Salford, United Kingdom;
authors.forename: James
authors.initials: J
authors.lastname: Ritchie
authors.affiliation: The Binding Site Group Ltd., Birmingham, United Kingdom;
authors.forename: Lakhvir K
authors.initials: LK
authors.lastname: Assi
authors.affiliation: The Binding Site Group Ltd., Birmingham, United Kingdom;
authors.forename: Anne
authors.initials: A
authors.lastname: Burmeister
authors.affiliation: Department of Renal Medicine, Salford Royal National Health Service Foundation Trust, Salford, United Kingdom;
authors.forename: Richard
authors.initials: R
authors.lastname: Hoefield
authors.affiliation: Department of Nephrology, Queen Elizabeth Hospital, Birmingham, United Kingdom; and Division of Immunity and Infection, College of Medical and Dental Science, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Cockwell
authors.affiliation: Department of Renal Medicine, Salford Royal National Health Service Foundation Trust, Salford, United Kingdom; philip.kalra@srft.nhs.uk.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Kalra
mesh_terms: D000367:Age Factors; D000368:Aged; D002318:Cardiovascular Diseases / Q000150:complications / Q000401:mortality; D002423:Cause of Death; D003404:Creatinine / Q000652:urine; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000097:blood*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000209:etiology / Q000652:urine; D008297:Male; D008875:Middle Aged; D010710:Phosphates / Q000097:blood; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011507:Proteinuria / Q000652:urine; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000150:complications / Q000401:mortality*; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D007147:Immunoglobulin Light Chains; D010710:Phosphates; D003404:Creatinine
keywords: CKD; ESRD; dialysis; mortality risk
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