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    1 Comment for this article
    RE: Association of glomerular hyperfiltration and cardiovascular risk in middle-aged healthy individuals
    Tomoyuki Kawada, MD | Nippon Medical School
    Dupuis et al. conducted a prospective study to determine the association between glomerular hyperfiltration and increased cardiovascular risk in 9515 healthy individuals, aged 40 to 69 years (1). Individuals with glomerular hyperfiltration (estimated glomerular filtration rate (eGFR) >95th percentile after stratification for sex and age) were compared with individuals with normal filtration rate (eGFR 25th-75th percentiles). Cardiovascular mortality and morbidities were defined as adverse cardiovascular events. Adjusted hazard ratio (HR) (95% confidence interval [CI]) of glomerular hyperfiltration for cardiovascular events was 1.88 (1.30-2.74), and the risk was similar to stage 3a chronic kidney disease. I have some concerns.

    hyperfiltration, defined as an increased eGFR, might be associated with early stages of chronic kidney disease in healthy and comorbid populations such as diabetes mellitus and established cardiovascular disease. Kanbay et al. conducted a systematic review to evaluate the implications of having renal hyperfiltration for cardiovascular disease and mortality risk (2). Although they speculated the mechanism of the association, there need further prospective/interventional studies for conducting a meta-analysis of the association.

    Regarding the first query, Reboldi et al. conducted a prospective study to investigate the effect of glomerular hyperfiltration on the risk of adverse cardiovascular outcome in 8794 participants, having mainly hypertension (3). Adjusted HRs (95% CIs) of high eGFR and low eGFR for cardiovascular events were 1.5 (1.2-2.1) and 2.0 (1.5-2.6), respectively. They clarified that there was a U-shaped relationship between eGFR and adverse cardiovascular outcome.

    Second, metabolic syndrome (MetS) is a major risk factor of cardiovascular disease. In addition, renal hyperfiltration (early-stage kidney damage) and hypofiltration (late-stage kidney damage) are common in patients with chronic renal disease. Raikou and Gavriil assessed the association between MetS and chronic renal disease (4). Odds ratios (ORs) (95% CIs) of MetS for low eGFR and albuminuria were 5.3 (1.6-17.8) and 3.2 (1.2-8.8), respectively. In patients with diabetes mellitus, OR (95% CIs) of MetS for albuminuria was 3.5 (1.1-11.3). They clarified that MetS was closely associated with chronic renal disease, but causal association and the significance of hyperfiltration should be specified by further study.

    Regarding the second query, Okada et al. investigated the association between renal hyperfiltration and hypofiltration with the number of metabolic syndrome (MetS) components (5). OR of the number of MetS components, from one to five, for hyperfiltration were 1.20, 1.40, 1.42, 1.41, and 1.77, respectively. In addition, OR of the number of MetS components, from one to five, for hypofiltration were 1.07, 1.25, 1.57, 1.89, and 2.21, respectively. These data present a dose-response relationship between MetS and kidney damage, and causal association should also be specified with special reference to each component of MetS.


    1. Dupuis ME, et al. JAMA Netw Open. 2020;3(4):e202377. doi: 10.1001/jamanetworkopen.2020.2377

    2. Kanbay M, et al. Diabetes Obes Metab. 2019;21(11):2368-2383. doi: 10.1111/dom.13831

    3. Reboldi G, et al. Kidney Int. 2018;93(1):195-203. doi: 10.1016/j.kint.2017.07.013

    4. Raikou VD, et al. Diseases. 2018;6(1):E12. doi: 10.3390/diseases6010012

    5. Okada R, et al. Nutr Metab Cardiovasc Dis. 2014;24(3):277-85. doi: 10.1016/j.numecd.2013.08.004
    Original Investigation
    April 10, 2020

    Association of Glomerular Hyperfiltration and Cardiovascular Risk in Middle-Aged Healthy Individuals

    Author Affiliations
    • 1Research Centre of the Hôpital du Sacré-Cœur de Montréal, Department of Medicine, Université de Montréal, Montréal, Canada
    • 2Research Centre of the Hôpital Maisonneuve-Rosemont, Department of Medicine, Université de Montréal, Montréal, Canada
    • 3CHU de Québec, Hôtel-Dieu de Québec, Université Laval, Québec, Canada
    JAMA Netw Open. 2020;3(4):e202377. doi:10.1001/jamanetworkopen.2020.2377
    Key Points español 中文 (chinese)

    Question  Is glomerular hyperfiltration associated with future cardiovascular events in healthy individuals?

    Findings  In this cohort study of 9515 patients with health information accessed through the CARTaGENE research platform, glomerular hyperfiltration was shown to be associated with increased risk of cardiovascular events in middle-aged healthy individuals.

    Meaning  This study found an increased cardiovascular disease risk associated with glomerular hyperfiltration in middle-aged healthy individuals, suggesting that glomerular hyperfiltration could be a useful cardiovascular biomarker in this population.


    Importance  Glomerular hyperfiltration is associated with increased risk of cardiovascular disease in high-risk conditions, but its significance in low-risk individuals is uncertain.

    Objective  To determine whether glomerular hyperfiltration is associated with increased cardiovascular risk in healthy individuals.

    Design, Setting, and Participants  This was a prospective population-based cohort study, for which enrollment took place from August 2009 to October 2010, with follow-up available through March 31, 2016. Analysis of the data took place in October 2019. The cohort was composed of 9515 healthy individuals, defined as individuals without hypertension, diabetes, cardiovascular disease, estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2, or statin and/or aspirin use, identified among 20 004 patients aged 40 to 69 years with health information accessed through the CARTaGENE research platform.

    Exposures  Individuals with glomerular hyperfiltration (eGFR >95th percentile after stratification for sex and age) were compared with individuals with normal filtration rate (eGFR 25th-75th percentiles).

    Main Outcomes and Measures  Adverse cardiovascular events were defined as a composite of cardiovascular mortality, myocardial infarction, unstable angina, heart failure, stroke, and transient ischemic attack. Risk of adverse cardiovascular events was assessed using Cox and fractional polynomial regressions and propensity score matching.

    Results  From the 20 004 CARTaGENE participants, 9515 healthy participants (4050 [42.6%] male; median [interquartile range] age, 50.4 [45.9-55.6] years) were identified. Among these, 473 had glomerular hyperfiltration (median [interquartile range] eGFR, 112 [107-115] mL/min/1.73 m2) and 4761 had a normal filtration rate (median [interquartile range] eGFR, 92 [87-97] mL/min/1.73 m2). Compared with the normal filtration rate, glomerular hyperfiltration was associated with an increased cardiovascular risk (hazard ratio, 1.88; 95% CI, 1.30-2.74; P = .001). Findings were similar with propensity score matching. The fractional polynomial regression showed that only the highest eGFR percentiles were associated with increased cardiovascular risk. The cardiovascular risk of individuals with glomerular hyperfiltration was similar to that of the 597 participants with an eGFR between 45 and 60 mL/min/1.73 m2 (hazard ratio, 0.90; 95% CI, 0.56-1.42; P = .64).

    Conclusions and Relevance  These findings suggest that glomerular hyperfiltration is independently associated with increased cardiovascular risk in middle-aged healthy individuals. This risk profile appears to be similar to stage 3a chronic kidney disease.