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.
Conflict of interest statement
Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis.Lancet. 2012 Nov 10;380(9854):1662-73. doi: 10.1016/S0140-6736(12)61350-6. Epub 2012 Sep 24. Lancet. 2012. PMID: 23013602 Free PMC article. Review.
Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without hypertension: a meta-analysis.Lancet. 2012 Nov 10;380(9854):1649-61. doi: 10.1016/S0140-6736(12)61272-0. Epub 2012 Sep 24. Lancet. 2012. PMID: 23013600 Free PMC article. Review.
Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality.JAMA. 2014 Jun 25;311(24):2518-2531. doi: 10.1001/jama.2014.6634. JAMA. 2014. PMID: 24892770 Free PMC article.
Comparison of risk prediction using the CKD-EPI equation and the MDRD study equation for estimated glomerular filtration rate.JAMA. 2012 May 9;307(18):1941-51. doi: 10.1001/jama.2012.3954. JAMA. 2012. PMID: 22570462 Free PMC article.
Lower estimated glomerular filtration rate and higher albuminuria are associated with mortality and end-stage renal disease. A collaborative meta-analysis of kidney disease population cohorts.Kidney Int. 2011 Jun;79(12):1331-40. doi: 10.1038/ki.2010.550. Epub 2011 Feb 2. Kidney Int. 2011. PMID: 21289598 Free PMC article.
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