title: Variability in estimated glomerular filtration rate values is a risk factor in chronic kidney disease progression among patients with diabetes.
abstract: BACKGROUND
  It is unknown whether variability of estimated Glomerular Filtration Rate (eGFR) is a risk factor for dialysis or death in patients with chronic kidney disease (CKD). This study aimed to evaluate variability of estimated Glomerular Filtration Rate (eGFR) as a risk factor for dialysis or death to facilitate optimum care among high risk patients.
  
  
  METHODS
  A longitudinal retrospective cohort study of 70,598 Veterans Health Administration veteran patients with diabetes and CKD (stage 3-4) in 2000 with up to 5 years of follow-up. VHA and Medicare files were linked to derive study variables. We used Cox proportional hazards models to evaluate association between time to initial dialysis/death and key independent variables: time-varying eGFR variability (measured by standard deviation (SD)) and eGFR means and slopes while adjusting for prior hospitalizations, and comorbidities.
  
  
  RESULTS
  There were 76.7% older than 65 years, 97.5% men, and 81.9% Whites. Patients were largely in early stage 3 (61.2%), followed by late stage 3 (28.9%), and stage 4 (9.9%); 29.1%, 46.8%, and 73.3%, respectively, died or had dialysis during the follow-up. eGFR SDs (median: 5.8, 5.1, and 4.0 ml/min/1.73 m(2)) and means (median: 54.1, 41.0, 27.2 ml/min/1.73 m(2)) from all two-year moving intervals decreased as CKD advanced; eGFR variability (relative to the mean) increased when CKD progressed (median coefficient of variation: 10.9, 12.8, and 15.4). Cox regressions revealed that one unit increase in a patient's standard deviation of eGFRs from prior two years was significantly associated with about 7% increase in risk of dialysis/death in the current year, similarly in all three CKD stages. This was after adjusting for concurrent means and slopes of eGFRs, demographics, prior hospitalization, and comorbidities. For example, the hazard of dialysis/death increased by 7.2% (hazard ratio:1.072; 95% CI = 1.067, 1.080) in early stage 3.
  
  
  CONCLUSIONS
  eGFR variability was independently associated with elevated risk of dialysis/death even after controlling for eGFR means and slopes.
authors.affiliation: Department of Veteran Affairs-New Jersey Health Care System, 385 Tremont Avenue, Mail Stop#15, East Orange, NJ, 07018, USA. chin-lin.tseng@va.gov.|Department of Preventive Medicine and Community Health, Rutgers University, New Jersey Medical School, Newark, NJ, USA. chin-lin.tseng@va.gov.
authors.forename: Chin-Lin
authors.initials: CL
authors.lastname: Tseng
authors.affiliation: Department of Medicine, University of Montreal, Montreal, QC, Canada. jean-philippe.lafrance@umontreal.ca.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Lafrance
authors.affiliation: Department of Biostatistics, Rutgers School of Public Health, Piscataway, NJ, USA. sl1020@sph.rutgers.edu.
authors.forename: Shou-En
authors.initials: SE
authors.lastname: Lu
authors.affiliation: Department of Veteran Affairs-New Jersey Health Care System, 385 Tremont Avenue, Mail Stop#15, East Orange, NJ, 07018, USA. Orysya.soroka@va.gov.
authors.forename: Orysya
authors.initials: O
authors.lastname: Soroka
authors.affiliation: Bedford VA Medical Center, Center for Health Quality, Outcomes and Economic Research, Bedford, MA, USA. drmiller@bu.edu.|Boston University, School of Public Health, Boston, MA, USA. drmiller@bu.edu.
authors.forename: Donald R
authors.initials: DR
authors.lastname: Miller
authors.affiliation: Department of Veteran Affairs-New Jersey Health Care System, 385 Tremont Avenue, Mail Stop#15, East Orange, NJ, 07018, USA. Miriam.maney@va.gov.
authors.forename: Miriam
authors.initials: M
authors.lastname: Maney
authors.affiliation: Department of Veteran Affairs-New Jersey Health Care System, 385 Tremont Avenue, Mail Stop#15, East Orange, NJ, 07018, USA. leonard.pogach@va.gov.|Department of Preventive Medicine and Community Health, Rutgers University, New Jersey Medical School, Newark, NJ, USA. leonard.pogach@va.gov.
authors.forename: Leonard M
authors.initials: LM
authors.lastname: Pogach
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002423:Cause of Death; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000175:diagnosis / Q000401:mortality / Q000628:therapy; D003928:Diabetic Nephropathies / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis* / Q000401:mortality* / Q000628:therapy; D012189:Retrospective Studies; D018570:Risk Assessment; D012737:Sex Factors; D015996:Survival Rate; D016896:Treatment Outcome