Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis
Open accessAbstract
Background Substantial controversy surrounds the use of estimated glomerular filtration rate (eGFR) and albuminuria to define chronic kidney disease and assign its stages. We undertook a meta-analysis to assess the independent and combined associations of eGFR and albuminuria with mortality.Methods In this collaborative meta-analysis of general population cohorts, we pooled standardised data for all-cause and cardiovascular mortality from studies containing at least 1000 participants and baseline information about eGFR and urine albumin concentrations. Cox proportional hazards models were used to estimate hazard ratios (HRs) for all-cause and cardiovascular mortality associated with eGFR and albuminuria, adjusted for potential confounders.Findings The analysis included 105,872 participants (730,577 person-years) from 14 studies with urine albumin-to-creatinine ratio (ACR) measurements and 1,128,310 participants (4,732,110 person-years) from seven studies with urine protein dipstick measurements. In studies with ACR measurements, risk of mortality was unrelated to eGFR between 75 mL/min/1.73 m(2) and 105 mL/min/1.73 m(2) and increased at lower eGFRs. Compared with eGFR 95 mL/min/1.73 m(2), adjusted HRs for all-cause mortality were 1.18 (95% CI 1.05-1.32) for eGFR 60 mL/min/1.73 m(2), 1.57 (1.39-1.78) for 45 mL/min/1.73 m(2), and 3.14 (2.39-4.13) for 15 mL/min/1.73 m(2). ACR was associated with risk of mortality linearly on the log-log scale without threshold effects. Compared with ACR 0.6 mg/mmol, adjusted HRs for all-cause mortality were 1.20 (1.15-1.26) for ACR 1.1 mg/mmol, 1.63 (1.50-1.77) for 3.4 mg/mmol, and 2.22 (1.97-2.51) for 33.9 mg/mmol. eGFR and ACR were multiplicatively associated with risk of mortality without evidence of interaction. Similar findings were recorded for cardiovascular mortality and in studies with dipstick measurements.Interpretation eGFR less than 60 mL/min/1.73 m(2) and ACR 1.1 mg/mmol (10 mg/g) or more are independent predictors of mortality risk in the general population. This study provides quantitative data for use of both kidney measures for risk assessment and definition and staging of chronic kidney disease.Funding Kidney Disease: Improving Global Outcomes (KDIGO), US National Kidney Foundation, and Dutch Kidney Foundation.
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A reduction in heart failure hospitalizations and a small reduction in myocardial infarction were observed in a pooled analysis of the CORONA and GISSI-HF trials.
“a reduction in HF hospitalizations [218,471], as well as a small reduction in MI, was observed in a pooled analysis of the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) and GISSI-HF trials [472].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [471]
In the adult population, decreasing GFR is associated with increased CVD risk, independent of other CV risk factors.
“In the adult population, a decreasing GFR is associated with an increased CVD risk, independent of other CV risk factors. 388-391”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [391]
CV mortality in patients with stage 3 and stage 4 CKD is two-fold and three-fold higher, respectively, compared with patients with normal renal function.
“The CV mortality in patients with stage 3 and stage 4 CKD is two-fold and three-fold higher, respectively, when compared with patients with normal renal function. 391”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [391]
Patients with stage 3-5 chronic kidney disease are at high or very high cardiovascular risk.
“Patients with stage 3-5 CKD have to be considered at high or very high CV risk.”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [391]
Cardiovascular mortality in patients with stage 3 and stage 4 chronic kidney disease is two-fold and three-fold higher, respectively, compared with patients with normal renal function.
“The CV mortality in patients with stage 3 and stage 4 CKD is two-fold and three-fold higher, respectively, when compared with patients with normal renal function.391”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [391]
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- Authors
- ‡
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- ‡
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2010-06
- Volume
- 375
- Issue
- 9731
- Pages
- 2073-2081
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- PMC
- PMC3993088
- OpenAlex
- W1570583414
- Cited by
- 4,200
- References
- 52
- Citations by year
- 2026: 188 · 2025: 250 · 2024: 296 · 2023: 286 · 2022: 298 · 2021: 280 · 2020: 270 · 2019: 238 · 2018: 230 · 2017: 273 · 2016: 273 · 2015: 265 · 2014: 282 · 2013: 264 · 2012: 231
- FWCI
- 34.26
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (submittedVersion)
- Funders
- Johns Hopkins University
- Nierstichting
- National Institutes of Health (n01hc045133-001, n01hc085079-024, n01hc015103-009, n01hc095169-003, n01hc085086-022, n01hc25195-41-0-1, n01hc55222-0-0-0, n01hc95159-40-0-1, n01hc075150-004, n01hc035129-010)
- National Institute on Aging (R01AG020098, R01AG007181, R01AG023629, R01AG028507, R01AG015928, R01AG027058)
- National Heart, Lung, and Blood Institute (HHSN268201 100012C, N01 HC085086, HHSN268201100007C, N01-HC095169, HHSN2682 01100008C, HH-SN-268201100006C, HHSN268201100011C, N01 HC085079, HHSN268201100005C, R01HL068140, N01 HC035129, HHSN268201100010C, N01-HC-095159, N01 HC015103, N01-HC-025195, HHSN268201200036C, HHSN26820 1100009C, N01 HC055222, R01HL043232, R01HL080295, N01 HC075150, N01 HC045133)
- National Eye Institute (U10EY006594)
- National Institute of Diabetes and Digestive and Kidney Diseases (K23DK067303, R01DK031801, K23DK002904, R01DK073217, U01DK035073)
- National Institute of Neurological Disorders and Stroke (U01NS041588)
- Topics
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Health Sciences › Medicine › Nephrology › Dialysis and Renal Disease Management
- Keywords
- estimated glomerular filtration rate, albuminuria, chronic kidney disease, all-cause mortality, cardiovascular mortality, albumin-creatinine ratio, general population cohort, CKD staging, kidney disease screening
- MeSH terms
- Aged, Albuminuria, Cardiovascular Diseases, Chronic Disease, Creatinine, Female, Glomerular Filtration Rate, Humans, Kidney Diseases, Male, Middle Aged, Mortality, Proportional Hazards Models
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