04194nas a2200517 4500008004100000022001400041245008700055210006900142260001600211300001200227490000800239520279100247653001503038653001003053653001603063653000903079653001603088653001903104653001103123653003103134653001103165653001103176653002803187653000903215653001603224653000903240653001603249100002103265700002503286700001903311700002703330700001703357700001803374700002103392700001903413700001903432700002203451700002303473700001903496700002303515700001803538700001803556700001803574710004803592856003603640 2012 eng d a1538-359800aAge and association of kidney measures with mortality and end-stage renal disease.0 aAge and association of kidney measures with mortality and endsta c2012 Dec 12 a2349-600 v3083 a

CONTEXT: 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.

DESIGN, SETTING, AND PARTICIPANTS: 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).

MAIN OUTCOME MEASURES: 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.

10aAdolescent10aAdult10aAge Factors10aAged10aAlbuminuria10aCohort Studies10aFemale10aGlomerular Filtration Rate10aHumans10aKidney10aKidney Failure, Chronic10aMale10aMiddle Aged10aRisk10aYoung Adult1 aHallan, Stein, I1 aMatsushita, Kunihiro1 aSang, Yingying1 aMahmoodi, Bakhtawar, K1 aBlack, Corri1 aIshani, Areef1 aKleefstra, Nanne1 aNaimark, David1 aRoderick, Paul1 aTonelli, Marcello1 aWetzels, Jack, F M1 aAstor, Brad, C1 aGansevoort, Ron, T1 aLevin, Adeera1 aWen, Chi-Pang1 aCoresh, Josef1 aChronic Kidney Disease Prognosis Consortium uhttps://chs-nhlbi.org/node/7380