Fast track — ArticlesAssociation of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis
Introduction
Chronic kidney disease is recognised as a major global public health problem.1, 2 The disease affects 10–16% of the adult population in Asia, Australia, Europe, and the USA,3, 4, 5, 6 and increases the risk of all-cause mortality, cardiovascular disease, and progression to kidney failure, even after accounting for traditional risk factors such as hypertension and diabetes mellitus.1, 7
The 2002 Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines2 define chronic kidney disease as persistent kidney damage, usually marked by albuminuria or reduced glomerular filtration rate (GFR), and assign disease stages on the basis of GFR. The KDOQI guidelines have encouraged research into the prognostic effect of chronic kidney disease and have contributed to increased awareness of it.8, 9 However, substantial controversy surrounds the use of GFR and albuminuria to define and assign stages to chronic kidney disease. Some investigators have proposed a lower GFR threshold (eg, GFR <45 mL/min/1·73 m2 vs <60 mL/min/1·73 m2) or age-specific or sex-specific GFR thresholds to define chronic kidney disease, use of higher urine albumin-to-creatinine ratio (ACR) as a marker of kidney damage (ACR ≥33·9 mg/mmol [≥300 mg/g] vs ≥3·4 mg/mmol [≥30 mg/g]), combining chronic kidney disease stages 1 and 2 (GFR 60 mL/min/1·73 m2 or more), or adding albuminuria within each stage determined by GFR.2, 8, 9, 10, 11
Several studies have reported the association between estimated GFR (eGFR) or albuminuria and clinical outcomes in the general population. However, most of these studies investigated only one measure at a time, did not investigate age-specific associations, and analysed broad eGFR categories (eg, <60 mL/min/1·73 m2 or ≥60 mL/min/1·73 m2). A few studies have dealt with some, but not all, of these issues.3, 12, 13, 14, 15, 16 Thus, there is a need for a comprehensive examination that adjusts for each measure, tests for their interactions on risk with narrow categories, and examines the association separately in younger and older individuals.
Kidney Disease: Improving Global Outcomes (KDIGO)17 has taken the lead in establishing the Chronic Kidney Disease Prognosis Consortium. The Consortium is tasked with compiling and meta-analysing the best available data to provide a more comprehensive assessment of the independent and combined associations of eGFR and albuminuria with mortality and kidney outcomes. The results of these assessments will have clear implications for improving the definition and staging of chronic kidney disease. The Consortium currently consists of 45 cohorts, which arise from general, high-risk, or chronic kidney disease populations. Separate reports will describe mortality and kidney outcomes by population type. This report describes the findings from a collaborative meta-analysis of the 21 general population cohorts for all-cause and cardiovascular mortality.
Section snippets
Search strategy and selection criteria
We searched PubMed on Aug 6, 2009, for studies published between 1966 and July, 2009, using the following combination of terms: (eGFR OR GFR OR glomerular filtration rate OR kidney function OR renal function) AND (albuminuria OR albumin to creatinine ratio OR ACR OR urinary albumin concentration OR UAC OR dipstick) AND (mortality OR ESRD OR end stage renal disease OR progressive chronic kidney disease OR acute kidney injury) AND (adult[MeSH]) AND (Humans[MeSH]). No language restrictions were
Results
Figure 1 shows the flow diagram of study selection for the analysis. Of the 21 studies included in the analysis, nine were from North America, six from Europe, five from Asia, and one from Australia. Characteristics of included studies are shown in table 1. Median follow-up time was 7·9 years (range 2·1–11·6). Overall, 1 234 182 participants (ACR studies, 105 872 participants; dipstick studies, 1 128 310 participants) were followed up for 5 462 687 person-years (ACR studies, 730 577
Discussion
This meta-analysis, which included more than 100 000 individuals with ACR measurements and 1·1 million participants with dipstick measurements from 21 general population cohorts, showed that eGFR and albuminuria were associated with all-cause mortality and cardiovascular mortality independently of each other and traditional cardiovascular risk factors. The consistency in both continuous and categorical models for eGFR and ACR shows that our findings are robust. With 21 studies from 14 countries
References (50)
- et al.
Chronic kidney disease as a global public health problem: approaches and initiatives—a position statement from Kidney Disease Improving Global Outcomes
Kidney Int
(2007) - et al.
All-cause mortality attributable to chronic kidney disease: a prospective cohort study based on 462 293 adults in Taiwan
Lancet
(2008) - et al.
Dissecting and refining the staging of chronic kidney disease
Kidney Int
(2009) - et al.
Definition and classification of CKD: the debate should be about patient prognosis—a position statement from KDOQI and KDIGO
Am J Kidney Dis
(2009) - et al.
Risk implications of the new CKD-EPI equation as compared to the MDRD Study equation for estimated glomerular filtration rate: the Atherosclerosis Risk in Communities (ARIC) Study
Am J Kidney Dis
(2010) - et al.
Comparison of the prevalence and mortality risk of CKD in Australia using the CKD Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) Study GFR estimating equations: The AusDiab (Australian Diabetes, Obesity and Lifestyle) Study
Am J Kidney Dis
(2010) - et al.
Chronic kidney disease as a predictor of cardiovascular disease (from the Framingham Heart Study)
Am J Cardiol
(2008) - et al.
Cystatin C and carotid intima-media thickness in asymptomatic adults: the Multi-Ethnic Study of Atherosclerosis (MESA)
Am J Kidney Dis
(2009) - et al.
Epidemiology of chronic kidney disease: results from a population of older adults in Germany
Prev Med
(2009) - et al.
CKD and mortality risk in older people: a community-based population study in the United Kingdom
Am J Kidney Dis
(2009)
Estimating GFR using serum cystatin C alone and in combination with serum creatinine: a pooled analysis of 3418 individuals with CKD
Am J Kidney Dis
K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification
Am J Kidney Dis
Prevalence of kidney damage in Australian adults: the AusDiab kidney study
J Am Soc Nephrol
International comparison of the relationship of chronic kidney disease prevalence and ESRD risk
J Am Soc Nephrol
Prevalence of chronic kidney disease in the United States
JAMA
Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention
Circulation
Staging of chronic kidney disease: time for a course correction
J Am Soc Nephrol
The case for using albuminuria in staging chronic kidney disease
J Am Soc Nephrol
Early identification and management of chronic kidney disease: summary of NICE guidance
BMJ
Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization
N Engl J Med
Age affects outcomes in chronic kidney disease
J Am Soc Nephrol
Association of kidney function and albuminuria with cardiovascular mortality in older vs younger individuals: the HUNT II Study
Arch Intern Med
Glomerular filtration rate, albuminuria, and risk of cardiovascular and all-cause mortality in the US population
Am J Epidemiol
Relation between kidney function, proteinuria, and adverse outcomes
JAMA
Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate
Ann Intern Med
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