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JAMA. 2012 Dec 12;308(22):2349-60.

Age and association of kidney measures with mortality and end-stage renal disease.

Collaborators (178)

Wright JT Jr, Appel LJ, Greene T, Astor BC, Chalmers J, MacMahon S, Woodward M, Arima H, Yatsuya H, Yamashita K, Toyoshima H, Tamakoshi K, Tonelli M, Hemmelgarn BR, Bello A, James MT, Coresh J, Astor BC, Matsushita K, Sang Y, Atkins RC, Polkinghorne KR, Chadban S, Shankar A, Klein R, Klein BE, Lee KE, Wang H, Wang F, Zhang L, Zuo L, Levin A, Djurdjev O, Tonelli M, Sacks FM, Curhan GC, Shlipak M, Peralta C, Katz R, Fried LF, Iso H, Kitamura A, Ohira T, Yamagishi K, Jafar TH, Islam M, Hatcher J, Poulter N, Chaturvedi N, Landray MJ, Emberson J, Townend JN, Wheeler DC, Rothenbacher D, Brenner H, Müller H, Schöttker B, Fox CS, Hwang SJ, Meigs JB, Perkins RM, Fluck N, Clark LE, Prescott GJ, Marks A, Black C, Cirillo M, Hallan S, Aasarød K, Øien CM, Radtke M, Irie F, Iso H, Sairenchi T, Yamagishi K, Smith DH, Weiss JW, Johnson ES, Thorp ML, Collins AJ, Vassalotti JA, Li S, Chen SC, Lee BJ, Wetzels JF, Blankestijn PJ, van Zuilen AD, Sarnak M, Levey AS, Inker LA, Menon V, Shlipak M, Sarnak M, Peralta C, Katz R, Kramer HJ, Kronenberg F, Kollerits B, Ritz E, Roderick P, Nitsch D, Fletcher A, Bulpitt C, Ishani A, Neaton JD, Froissart M, Stengel B, Metzger M, Haymann JP, Houillier P, Flamant M, Astor BC, Coresh J, Matsushita K, Ohkubo T, Metoki H, Nakayama M, Kikuya M, Imai Y, Iseki K, Nelson RG, Knowler WC, Gansevoort RT, de Jong PE, Mahmoodi BK, Heerspink HJ, Jassal SK, Barrett-Connor E, Bergstrom J, Heerspink HJ, Brenner BE, de Zeeuw D, Warnock DG, Muntner P, Judd S, McClellan W, Jee SH, Kimm H, Jo J, Mok Y, Lim JE, Rossing P, Parving HH, Tangri N, Naimark D, Wen CP, Wen SF, Tsao CK, Tsai MK, Ärnlöv J, Lannfelt L, Larsson A, Bilo HJ, Joosten H, Kleefstra N, Groenier KH, Drion I, Astor BC, Coresh J, Gansevoort RT, Hemmelgarn BR, de Jong PE, Levey AS, Levin A, Matsushita K, Wen CP, Woodward M, Ballew SH, Coresh J, Grams M, Mahmoodi BK, Matsushita K, Sang Y, Woodward M, Camarata L, Hui X, Seltzer J, Winegrad H.

Author information

1
Division of Nephrology, Department of Medicine, St Olav University Hospital, and Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.

Abstract

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.

PMID:
23111824
PMCID:
PMC3936348
DOI:
10.1001/jama.2012.16817
[Indexed for MEDLINE]
Free PMC Article

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