title: Age and association of kidney measures with mortality and end-stage renal disease.
abstract: BACKGROUND
  Chronic kidney disease (CKD) is prevalent in older individuals, but the risk implications of low estimated glomerular filtration rate (eGFR) and high albuminuria across the full age range are controversial.
  
  
  OBJECTIVE
  To evaluate possible effect modification (interaction) by age of the association of eGFR and albuminuria with clinical risk, examining both relative and absolute risks.
  
  
  METHODS
  Individual-level meta-analysis including 2,051,244 participants from 33 general population or high-risk (of vascular disease) cohorts and 13 CKD cohorts from Asia, Australasia, Europe, and North/South America, conducted in 1972-2011 with a mean follow-up time of 5.8 years (range, 0-31 years).
  
  
  METHODS
  Hazard ratios (HRs) of mortality and end-stage renal disease (ESRD) according to eGFR and albuminuria were meta-analyzed across age categories after adjusting for sex, race, cardiovascular disease, diabetes, systolic blood pressure, cholesterol, body mass index, and smoking. Absolute risks were estimated using HRs and average incidence rates.
  
  
  RESULTS
  Mortality (112,325 deaths) and ESRD (8411 events) risks were higher at lower eGFR and higher albuminuria in every age category. In general and high-risk cohorts, relative mortality risk for reduced eGFR decreased with increasing age; eg, adjusted HRs at an eGFR of 45 mL/min/1.73 m2 vs 80 mL/min/1.73 m2 were 3.50 (95% CI, 2.55-4.81), 2.21 (95% CI, 2.02-2.41), 1.59 (95% CI, 1.42-1.77), and 1.35 (95% CI, 1.23-1.48) in age categories 18-54, 55-64, 65-74, and ≥75 years, respectively (P <.05 for age interaction). Absolute risk differences for the same comparisons were higher at older age (9.0 [95% CI, 6.0-12.8], 12.2 [95% CI, 10.3-14.3], 13.3 [95% CI, 9.0-18.6], and 27.2 [95% CI, 13.5-45.5] excess deaths per 1000 person-years, respectively). For increased albuminuria, reduction of relative risk with increasing age was less evident, while differences in absolute risk were higher in older age categories (7.5 [95% CI, 4.3-11.9], 12.2 [95% CI, 7.9-17.6], 22.7 [95% CI, 15.3-31.6], and 34.3 [95% CI, 19.5-52.4] excess deaths per 1000 person-years, respectively by age category, at an albumin-creatinine ratio of 300 mg/g vs 10 mg/g). In CKD cohorts, adjusted relative hazards of mortality did not decrease with age. In all cohorts, ESRD relative risks and absolute risk differences at lower eGFR or higher albuminuria were comparable across age categories.
  
  
  CONCLUSIONS
  Both low eGFR and high albuminuria were independently associated with mortality and ESRD regardless of age across a wide range of populations. Mortality showed lower relative risk but higher absolute risk differences at older age.
authors.affiliation: Division of Nephrology, Department of Medicine, St Olav University Hospital, and Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Stein I
authors.initials: SI
authors.lastname: Hallan
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Matsushita
authors.forename: Yingying
authors.initials: Y
authors.lastname: Sang
authors.forename: Bakhtawar K
authors.initials: BK
authors.lastname: Mahmoodi
authors.forename: Corri
authors.initials: C
authors.lastname: Black
authors.forename: Areef
authors.initials: A
authors.lastname: Ishani
authors.forename: Nanne
authors.initials: N
authors.lastname: Kleefstra
authors.forename: David
authors.initials: D
authors.lastname: Naimark
authors.forename: Paul
authors.initials: P
authors.lastname: Roderick
authors.forename: Marcello
authors.initials: M
authors.lastname: Tonelli
authors.forename: Jack F M
authors.initials: JF
authors.lastname: Wetzels
authors.forename: Brad C
authors.initials: BC
authors.lastname: Astor
authors.forename: Ron T
authors.initials: RT
authors.lastname: Gansevoort
authors.forename: Adeera
authors.initials: A
authors.lastname: Levin
authors.forename: Chi-Pang
authors.initials: CP
authors.lastname: Wen
authors.forename: Josef
authors.initials: J
authors.lastname: Coresh
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000419:Albuminuria; D015331:Cohort Studies; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D007676:Kidney Failure, Chronic / Q000401:mortality* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D012306:Risk; D055815:Young Adult