Original InvestigationPathogenesis and Treatment of Kidney DiseaseProteinuria and Stroke: A Meta-analysis of Cohort Studies
Section snippets
Search Strategy and Selection Criteria
The Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines for the conduct of meta-analyses of observational cohort studies14 were followed. Relevant studies published between 1966 and November 2006 were identified from MEDLINE, EMBASE, and CINAHL by using relevant text words and medical subject headings that included all spellings of “proteinuria,” “albuminuria,” “microalbuminuria,” and “macroalbuminuria” and combined these with all spellings of “stroke,” “apoplexy,”
Literature Search
The literature search yielded 3,028 articles, of which 220 were reviewed in full. Ten published studies5, 6, 7, 8, 9, 10, 11, 16, 19, 20 including information for 140,231 participants and 3,266 stroke events (37.0% fatal) were eligible for inclusion in the analysis. A flow chart detailing the process of study identification and selection is shown in Fig 1, and characteristics of the included studies are listed in Table 2. Two studies5, 19 reported the effects of macroalbuminuria compared with
Discussion
The key finding from this systematic overview, which included data for more than 3,000 stroke events in 140,000 participants, is that the presence of proteinuria confers a 50% to 70% greater risk of stroke. This association was uniformly consistent across important subgroups characterized by sex, ethnicity, and diabetes status and was apparent in studies that had adjusted for known cardiovascular risk factors, most notably blood pressure. Although the potential for residual confounding remains,
Acknowledgements
Support: None.
Financial Disclosure: Toshiharu Ninomiya holds a Banyu Life Science Foundation Fellowship and International Society of Hypertension Visiting Postdoctoral Award from the Foundation for High Blood Pressure Research in Australia; Vlado Perkovic holds a fellowship of Heart Foundation of Australia and the Royal Australasian College of Physicians Pfizer Cardiovascular Research fellowship; Alan Cass holds a Senior Research Fellowship from the NHMRC of Australia; and Craig Anderson holds
References (37)
- et al.
The relationships of proteinuria, serum creatinine, glomerular filtration rate with cardiovascular disease mortality in Japanese general population
Kidney Int
(2006) - et al.
Mortality from coronary heart disease and cerebrovascular disease and associated risk factors in diabetic patients in Osaka District, Japan
Diabetes Res Clin Pract
(1995) - et al.
Prevalence of albuminuria in Australia: The AusDiab Kidney Study
Kidney Int Suppl
(2004) - et al.
The relationship of cardiovascular risk factors to microalbuminuria in older adults with or without diabetes mellitus or hypertension: The Cardiovascular Health Study
Am J Kidney Dis
(2004) - et al.
Association between high-normal albuminuria and risk factors for cardiovascular and renal disease in essential hypertensive men
Am J Kidney Dis
(2002) - et al.
Urine albumin/creatinine ratio and echocardiographic left ventricular structure and function in hypertensive patients with electrocardiographic left ventricular hypertrophy: The LIFE StudyLosartan Intervention for Endpoint Reduction
Am Heart J
(2002) - et al.
Relation between albumin in the urine and electrocardiographic markers of myocardial ischemia in patients without diabetes mellitus
Am J Cardiol
(2001) WHO in collaboration with the US Centers for Disease Control and Prevention: The Atlas of Heart Disease and StrokeGlobal Burden of Stroke
Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)
JAMA
(2001)Joint effects of systolic blood pressure and serum cholesterol on cardiovascular disease in the Asia Pacific region
Circulation
(2005)
The effects of diabetes on the risks of major cardiovascular diseases and death in the Asia-Pacific region
Diabetes Care
The risk of cardiovascular disease mortality associated with microalbuminuria and gross proteinuria in persons with older-onset diabetes mellitus
Arch Intern Med
Proteinuria predicts stroke and other atherosclerotic vascular disease events in nondiabetic and non-insulin-dependent diabetic subjects
Stroke
Proteinuria and risk for stroke and coronary heart disease during 27 years of follow-up: the Honolulu Heart Program
Arch Intern Med
A 15.5-year follow-up study of stroke in a Japanese provincial city: The Shibata Study
Stroke
Proteinuria as a biomarker: Risk of subsequent morbidity and mortality
Environ Res
Albuminuria and renal insufficiency prevalence guides population screening: Results from the NHANES III
Kidney Int
Meta-analysis of Observational Studies in Epidemiology: A proposal for reportingMeta-analysis Of Observational Studies in Epidemiology (MOOSE) group
JAMA
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2021, Kidney InternationalCitation Excerpt :Risk appears to be greater for patients treated with hemodialysis, compared with those on peritoneal dialysis.7 Patients with proteinuria also represent a high-risk subgroup, with a previous meta-analysis showing that such individuals were at a 71% higher risk of stroke compared with those without proteinuria.8 Recent data suggest that proteinuria may be a better predictor of stroke risk in CKD than estimated glomerular filtration rate (eGFR), possibly as an indicator of microvascular disease.9
Originally published online as doi:10.1053/j.ajkd.2008.08.032 on December 15, 2008.