title: Detection of chronic kidney disease with creatinine, cystatin C, and urine albumin-to-creatinine ratio and association with progression to end-stage renal disease and mortality.
abstract: BACKGROUND
  A triple-marker approach for chronic kidney disease (CKD) evaluation has not been well studied.
  
  
  OBJECTIVE
  To evaluate whether combining creatinine, cystatin C, and urine albumin-to-creatinine ratio (ACR) would improve identification of risks associated with CKD compared with creatinine alone.
  
  
  METHODS
  Prospective cohort study involving 26,643 US adults enrolled in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study from January 2003 to June 2010. Participants were categorized into 8 groups defined by estimated glomerular filtration rate (GFR) determined by creatinine and by cystatin C of either <60 or ≥60 mL/min/1.73 m(2) and ACR of either <30 or ≥30 mg/g.
  
  
  METHODS
  All-cause mortality and incident end-stage renal disease with median follow-up of 4.6 years.
  
  
  RESULTS
  Participants had a mean age of 65 years, 40% were black, and 54% were women. Of 26,643 participants, 1940 died and 177 developed end-stage renal disease. Among participants without CKD defined by creatinine, 24% did not have CKD by either ACR or cystatin C. Compared with those with CKD defined by creatinine alone, the hazard ratio for death in multivariable-adjusted models was 3.3 (95% confidence interval [CI], 2.0-5.6) for participants with CKD defined by creatinine and ACR; 3.2 (95% CI, 2.2-4.7) for those with CKD defined by creatinine and cystatin C, and 5.6 (95% CI, 3.9-8.2) for those with CKD defined by all biomarkers. Among participants without CKD defined by creatinine, 3863 (16%) had CKD detected by ACR or cystatin C. Compared with participants who did not have CKD by any measure, the HRs for mortality were 1.7 (95% CI, 1.4-1.9) for participants with CKD defined by ACR alone, 2.2 (95% CI, 1.9-2.7) for participants with CKD defined by cystatin C alone, and 3.0 (95% CI, 2.4-3.7) for participants with CKD defined by both measures. Risk of incident end-stage renal disease was higher among those with CKD defined by all markers (34.1 per 1000 person-years; 95% CI, 28.7-40.5 vs 0.33 per 1000 person-years; 95% CI, 0.05-2.3) for those with CKD defined by creatinine alone. The second highest end-stage renal disease rate was among persons missed by the creatinine measure but detected by both ACR and cystatin C (rate per 1000 person-years, 6.4; 95% CI, 3.6-11.3). Net reclassification improvement for death was 13.3% (P < .001) and for end-stage renal disease was 6.4% (P < .001) after adding estimated GFR cystatin C in fully adjusted models with estimated GFR creatinine and ACR.
  
  
  CONCLUSIONS
  Adding cystatin C to the combination of creatinine and ACR measures improved the predictive accuracy for all-cause mortality and end-stage renal disease.
authors.affiliation: Department of Medicine, San Francisco VA Medical Center, San Francisco, California, USA. carmenalicia.peralta@ucsf.edu
authors.forename: Carmen A
authors.initials: CA
authors.lastname: Peralta
authors.forename: Michael G
authors.initials: MG
authors.lastname: Shlipak
authors.forename: Suzanne
authors.initials: S
authors.lastname: Judd
authors.forename: Mary
authors.initials: M
authors.lastname: Cushman
authors.forename: William
authors.initials: W
authors.lastname: McClellan
authors.forename: Neil A
authors.initials: NA
authors.lastname: Zakai
authors.forename: Monika M
authors.initials: MM
authors.lastname: Safford
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.forename: Paul
authors.initials: P
authors.lastname: Muntner
authors.forename: David
authors.initials: D
authors.lastname: Warnock
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000419:Albuminuria / Q000652:urine*; D015415:Biomarkers / Q000032:analysis; D002423:Cause of Death; D003404:Creatinine / Q000097:blood*; D055316:Cystatin C / Q000097:blood*; D018450:Disease Progression; D005260:Female; D005544:Forecasting; D005919:Glomerular Filtration Rate; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000401:mortality* / Q000473:pathology / Q000652:urine*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012306:Risk
chemical_list: D015415:Biomarkers; D055316:Cystatin C; D003404:Creatinine