Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis
Open accessAbstract
Background Chronic kidney disease is characterised by low estimated glomerular filtration rate (eGFR) and high albuminuria, and is associated with adverse outcomes. Whether these risks are modified by diabetes is unknown. Methods We did a meta-analysis of studies selected according to Chronic Kidney Disease Prognosis Consortium criteria. Data transfer and analyses were done between March, 2011, and June, 2012. We used Cox proportional hazards models to estimate the hazard ratios (HR) of mortality and end-stage renal disease (ESRD) associated with eGFR and albuminuria in individuals with and without diabetes. Findings We analysed data for 1 024 977 participants (128 505 with diabetes) from 30 general population and high-risk cardiovascular cohorts and 13 chronic kidney disease cohorts. In the combined general population and high-risk cohorts with data for all-cause mortality, 75 306 deaths occurred during a mean follow-up of 8·5 years (SD 5·0). In the 23 studies with data for cardiovascular mortality, 21 237 deaths occurred from cardiovascular disease during a mean follow-up of 9·2 years (SD 4·9). In the general and high-risk cohorts, mortality risks were 1·2–1·9 times higher for participants with diabetes than for those without diabetes across the ranges of eGFR and albumin-to-creatinine ratio (ACR). With fixed eGFR and ACR reference points in the diabetes and no diabetes groups, HR of mortality outcomes according to lower eGFR and higher ACR were much the same in participants with and without diabetes (eg, for all-cause mortality at eGFR 45 mL/min per 1·73 m2 [νs 95 mL/min per 1·73 m2], HR 1·35; 95% CI 1·18–1·55; νs 1·33; 1·19–1·48 and at ACR 30 mg/g [νs 5 mg/g], 1·50; 1·35–1·65 νs 1·52; 1·38–1·67). The overall interactions were not significant. We identified much the same findings for ESRD in the chronic kidney disease cohorts. Interpretation Despite higher risks for mortality and ESRD in diabetes, the relative risks of these outcomes by eGFR and ACR are much the same irrespective of the presence or absence of diabetes, emphasising the importance of kidney disease as a predictor of clinical outcomes.
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Among people with type 1 or type 2 diabetes, the presence of CKD markedly increases cardiovascular risk and health care costs.
“In addition, among people with type 1 or type 2 diabetes, the presence of CKD markedly increases cardiovascular risk and health care costs (6).”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [6]
The Results report that cardiovascular mortality generally increased with lower eGFR and higher albuminuria in participants with diabetes. The paper does not report health care costs or distinguish findings for type 1 versus type 2 diabetes, so those parts of the claim are unsupported. (LLM, conf=0.90)
Experimental — accuracy not yet measuredAt any eGFR, the degree of albuminuria is associated with risk of cardiovascular disease, CKD progression, and mortality.
“At any eGFR, the degree of albuminuria is associated with risk of cardiovascular disease (CVD), CKD progression, and mortality (6).”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [6]
The Results report that all-cause and cardiovascular mortality generally increased with higher albuminuria categories across eGFR categories. The Discussion also identifies albuminuria as a predictor of end-stage renal disease. The study measured cardiovascular mortality and end-stage renal disease, not cardiovascular disease generally or all forms of CKD progression. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThe risks of progression towards kidney failure and cardiovascular events increase with severity and stage of chronic kidney disease.
“and the risks of progression towards kidney failure and cardiovascular events increase with severity and stage of CKD.6”
From Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis (2022) · cites this paper as [6]
The Results (page not available in our copy) report that ESRD risk rose with worsening kidney measures and that cardiovascular mortality generally increased with lower eGFR and higher albuminuria categories. The paper analyzes cardiovascular death, not cardiovascular events more broadly, so that part of the claim exceeds its findings. (LLM, conf=0.87)
Experimental — accuracy not yet measuredAmong people with type 1 or type 2 diabetes, the presence of CKD markedly increases cardiovascular risk and health care costs.
“In addition, among people with type 1 or type 2 diabetes, the presence of CKD markedly increases cardiovascular risk and health care costs (6).”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [6]
The Introduction and Discussion report increased cardiovascular mortality risk in people with diabetes and CKD. The paper does not report health care costs or separate findings for type 1 and type 2 diabetes; its measured cardiovascular outcome is mortality, not cardiovascular risk more broadly. The supplied passages have no page numbers. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAt any eGFR, the degree of albuminuria is associated with risk of cardiovascular disease, CKD progression, and mortality.
“At any eGFR, the degree of albuminuria is associated with risk of cardiovascular disease (CVD), CKD progression, and mortality (6).”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [6]
The Results (page not available in our copy) associate higher albuminuria with greater all-cause and cardiovascular mortality across eGFR–albuminuria categories; they also report increasing ESRD risk with higher albuminuria. The paper examines cardiovascular mortality rather than cardiovascular disease generally, and ESRD rather than CKD progression more broadly, so those parts of the claim exceed its reported outcomes. (LLM, conf=0.85)
Experimental — accuracy not yet measured
CKD markedly amplifies risks of ASCVD, heart failure, cardiovascular death, and all-cause mortality among people with diabetes.
“Moreover, CKD markedly amplifies risks of ASCVD, heart failure (HF), cardiovascular death, and all-cause mortality among people with diabetes (7,8).”
From Diabetes management in chronic kidney disease: a consensus report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO) (2022) · cites this paper as [8]
The Introduction and Discussion state that people with diabetes and CKD have increased risks of cardiovascular and all-cause mortality. The Methods list heart failure and myocardial infarction among causes of cardiovascular death, but the paper does not report separate risks of heart failure or ASCVD. No page numbers are available in our copy. (LLM, conf=0.89)
Experimental — accuracy not yet measuredPeople with diabetes and CKD are at high risk for kidney failure, atherosclerotic cardiovascular disease, heart failure, and premature mortality.
“People with diabetes and chronic kidney disease (CKD) are at high risk for kidney failure, atherosclerotic cardiovascular disease, heart failure, and premature mortality.”
From Diabetes management in chronic kidney disease: a consensus report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO) (2022) · cites this paper as [8]
The Introduction states that people with diabetes and CKD have greatly increased risks of kidney failure, cardiovascular mortality, and all-cause mortality; the Discussion also reports higher absolute risks of ESRD and death in this group. The Methods (Procedures; page not provided) define cardiovascular mortality to include deaths from myocardial infarction, heart failure, and stroke, but the paper does not establish separate risks of developing atherosclerotic cardiovascular disease or heart failure. (LLM, conf=0.88)
Experimental — accuracy not yet measuredChronic kidney disease is often progressive, with decreased glomerular filtration rate and albuminuria as key risk factors for subsequently developing kidney failure.
“Chronic kidney disease (CKD) is often progressive, with decreased glomerular filtration rate (GFR) and the presence of albuminuria representing key risk factors for subsequently developing kidney failure.1”
From Empagliflozin in Patients with Chronic Kidney Disease (2023) · cites this paper as [1]
UACR is a continuous measurement, and differences within the normal and abnormal ranges are associated with kidney and cardiovascular outcomes.
“However, UACR is a continuous measurement, and differences within the normal and abnormal ranges are associated with kidney and cardiovascular outcomes (6,10,11).”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [6]
UACR is a continuous measurement, and differences within the normal and abnormal ranges are associated with kidney and cardiovascular outcomes.
“However, UACR is a continuous measurement, and differences within the normal and abnormal ranges are associated with kidney and cardiovascular outcomes (6,11,12).”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [6]
The risk of patients developing cardiovascular and renal events increases as DM and CKD progresses, potentially reaching renal and cardiac endpoint events such as ESRD, heart failure, MI and stroke.
“Moreover, the risk of patients developing cardiovascular and renal events increase as DM and CKD progresses, potentially reaching renal and cardiac endpoint events such as ESRD, heart failure, myocardial infarction (MI) and stroke [11–14].”
Both reduced eGFR and presence of albuminuria are independently associated with increased risk of cardiovascular disease and mortality in a graded fashion.
“Both a reduction in eGFR and the presence of albuminuria are independently associated with an increased risk of CVD and mortality in a graded fashion [8,9].”
From Glucagon-like peptide-1 receptor agonists in diabetic kidney disease: a review of their kidney and heart protection (2023) · cites this paper as [9]
Albuminuria is an early marker of nephropathy and predicts both risk of kidney failure and cardiovascular disease independently of eGFR.
“Albuminuria is an early marker of nephropathy and predicts both risk of kidney failure and CVD independently of eGFR.43,682”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [43]
An eGFR <60 mL/min/1.73 m2 is associated with increased risk of chronic kidney disease progression and cardiovascular disease.
“This level of eGFR is associated with increased risk of CKD progression and CVD.43,679,680”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [43]
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Self-citation2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes.
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Self-citation2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization
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Self-citationKidney disease and increased mortality risk in type 2 diabetes
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Liraglutide and renal outcomes in type 2 diabetes
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Diabetic kidney disease: a report from an ADA Consensus Conference
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“( 54–56) As patients with decreased eGFR are at the highest absolute risk of kidney disease progression, (57) our findings should encourage the initiation of SGLT2 inhibitors in patients with CKD down to an eGFR of 20 mL/min/1·73m 2 with continued use below this level.”
Self-citationCystatin C versus Creatinine in Determining Risk Based on Kidney Function
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Self-citationGlomerular hyperfiltration in diabetes: mechanisms, clinical significance, and treatment
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Self-citationDiabetic Kidney Disease: A Report From an ADA Consensus Conference
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“As well as indicating increased cardiovascular risk in both T1DM and T2DM,20,21 the traditional paradigm is that the onset of moderately increased albuminuria (A2), previously termed microalbuminuria, predicts the onset of established DN.22-25 A number of studies have reported this relationship in both T1DM and T2DM.”
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Self-citationEpidemiology and risk of cardiovascular disease in populations with chronic kidney disease
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Cardiovascular disease in dialysis patients
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2021 ESC Guidelines on cardiovascular disease prevention in clinical practice
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“Manhattan plots for CKD, eGFRcys, and eGFRcrea in diabetes are shown in Figure 1B, Figure 1C, and Supplementary Fig.”
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11. Microvascular Complications and Foot Care: <i>Standards of Medical Care in Diabetes—2021</i>
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CKD: A Call for an Age-Adapted Definition
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“Compared with other types of diabetic patients, DN patients have a higher mortality rate, and most of the deaths are due to cardiovascular events [8].”
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Self-citationObservational research--opportunities and limitations
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SGLT2 Inhibitors: A Review of Their Antidiabetic and Cardioprotective Effects
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“CKD increases CV risk in people with and without DM [83].”
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Lifetime Incidence of CKD Stages 3–5 in the United States
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Finerenone and cardiovascular outcomes in patients with chronic kidney disease and type 2 diabetes
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Self-citation11. Chronic Kidney Disease and Risk Management: <i>Standards of Medical Care in Diabetes—2022</i>
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Cardiovascular Complications of Diabetic Kidney Disease
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11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2023
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“These patients are at high risk of CKD progression and cardiovascular disease (CVD).(4,5) Comprehensive management includes a foundation of lifestyle intervention and risk factor management, with additional pharmacotherapy in selected patients (Figure 2).”
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11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2024
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Complications of chronic kidney disease: current state, knowledge gaps, and strategy for action
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“Cardiovascular complications: CVD represents the leading cause of mortality in CKD patients, and the prevalence and burden of this complication increases with declining kidney function (Figures 1 and 2).(8,14) For example, the risk of mortality from CVD is 8.”
BackgroundDiabetic kidney disease: a clinical update from Kidney Disease: Improving Global Outcomes
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Self-citation11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025
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“Comorbidities are important because they may impact on treatment burden, medications management, quality of life, and survival [4–6].”
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“CKD can often be a progressive condition, with proteinuria representing a significant risk factor for more rapid decline in kidney function [6].”
Early chronic kidney disease–mineral bone disorder stimulates vascular calcification
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“Impaired renal function, as determined from the estimated glomerular filtration rate (eGFR), is also associated with cardiovascular events and mortality (Fox et al. 2012; Go et al. 2004; Sarnak et al. 2003).”
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Oxidative Stress and Inflammation in Renal and Cardiovascular Complications of Diabetes
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“Individuals with diabetes and kidney disease have an increased risk of CVD and premature death [67].”
BackgroundThe double challenge of resistant hypertension and chronic kidney disease
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The Rehabilitation Role in Chronic Kidney and End Stage Renal Disease
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Rationale and design of the Kidney Precision Medicine Project
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Inflammation and Oxidative Stress in Chronic Kidney Disease and Dialysis Patients
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Roles of Nrf2 in Protecting the Kidney from Oxidative Damage
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“Since then, CDDO-ME has been investigated to develop novel medicines against diabetic nephropathy, for which no effective medicine has been established despite its high morbidity [113,114].”
BackgroundCongestive Nephropathy: A Neglected Entity? Proposal for Diagnostic Criteria and Future Perspectives
Husain‐Syed, F., Gröne, H., Aßmus, B., Bauer, P., Gall, H. J., Seeger, W., Ghofrani, H. A., Ronco, C., & Birk, H. (2020) · ESC Heart Failure · doi:10.1002/ehf2.13118 · Cited by 174 · see citing works
Matsushita, K., Ballew, S. H., Coresh, J., Arima, H., Ärnlöv, J., Círillo, M., Ebert, N., Hiramoto, J. S., Kimm, H., Shlipak, M. G., et al. (2017) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(17)30183-3 · Cited by 171 · see citing works
Self-citationThe link between chronic kidney disease and cardiovascular disease.
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Increased cardiovascular mortality associated with gout: a systematic review and meta-analysis
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Diabetes and CKD in the United States population, 2009-2014
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Carbamylated low-density lipoprotein induces endothelial dysfunction
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“Although mortality declined during the last years, the morbidity associated with atherosclerosis and its consequences remains high, particularly in patients with diabetes and/or chronic kidney disease (CKD).(2,3)”
BackgroundTargeting Vascular Calcification in Chronic Kidney Disease
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“Clustering of traditional risk factors such as type 2 diabetes mellitus and hypertension were originally believed to drive propensity for CVD in these patients; however, meta-analyses have consistently identified significant residual, CKDspecific risk (17,18).”
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Diabetes with early kidney involvement may shorten life expectancy by 16 years
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- Authors
- Fox, C. S., Matsushita, K., Woodward, M., Bilo, H. J., Chalmers, J., Heerspink, H. J. L., Lee, B. J., Perkins, R. M., Rossing, P., Sairenchi, T., Tonelli, M., Vassalotti, J. A., Yamagishi, K., Coresh, J., de Jong, P. E., Wen, C.-P., & Nelson, R. G.
- Affiliations
- Brigham and Women's Hospital (US)
- Johns Hopkins University (US)
- The University of Sydney (AU)
- Isala (NL)
- University of Groningen (NL)
- Kaiser Permanente (US)
- Geisinger Medical Center (US)
- Aarhus University (DK)
- Dokkyo Medical University (JP)
- University of Alberta (CA)
- National Kidney Foundation (US)
- University of Tsukuba (JP)
- National Health Research Institutes (TW)
- National Institutes of Health (US)
- Corresponding author
- Coresh, Josef
- ORCID
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2012-11
- Volume
- 380
- Issue
- 9854
- Pages
- 1662-1673
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- PMC
- PMC3771350
- OpenAlex
- W2111663222
- Semantic Scholar
- 53ede2fd1666f72bf5b06d881d692008d02a2f63
- Cited by
- 1,401
- References
- 59
- Citations by year
- 2026: 72 · 2025: 114 · 2024: 105 · 2023: 128 · 2022: 125 · 2021: 138 · 2020: 120 · 2019: 84 · 2018: 76 · 2017: 81 · 2016: 88 · 2015: 95 · 2014: 96 · 2013: 65 · 2012: 12
- FWCI
- 12.45
- Type
- journal article
- Language
- en
- Open access
- green
- research.rug.nl
- Licence
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- Amgen
- Sanofi
- Novo Nordisk
- Servier
- 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, HHSN268201100007I, N01 HC085086, HHSN268201100007C, N01-HC095169, HHSN2682 01100008C, HH-SN-268201100006C, HHSN268201100011C, HHSN2682011-00005I, N01 HC085079, HHSN2682011-00009I, HHSN268201100005C, R01HL068140, N01 HC035129, HHSN268201100005G, HHSN268201100010C, N01-HC-095159, N01 HC015103, HHSN268201100011I, N01-HC-025195, HHSN268201200036C, HHSN26820 1100009C, N01 HC055222, HHSN2682011-00008I, 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 › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Keywords
- chronic kidney disease, diabetes mellitus, estimated glomerular filtration rate, albuminuria, albumin-creatinine ratio, end-stage renal disease, all-cause mortality, cardiovascular mortality, kidney disease progression, CKD risk stratification, CKD-EPI equation
- MeSH terms
- Aged, Albuminuria, Cardiovascular Diseases, Cause of Death, Diabetic Nephropathies, Female, Glomerular Filtration Rate, Humans, Kidney Failure, Chronic, Male, Middle Aged, Risk Factors
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