In a study of 8.7 million Canadian adults, subclinical kidney dysfunction significantly linked with a higher rate of major adverse cardiovascular events (MACE) in people aged 18-39 years, a finding that supports routine renal screening in people as young as age 18 with low or very low risk.
Researchers conducted a retrospective analysis of 8.7 million adults aged 18-65 years residing in Ontario, Canada, who underwent estimated glomerular filtration rate (eGFR) measurements during 2008-2020 in a provincial health insurance database with at least 1 year follow-up and no history of kidney disease.
Primary outcome was time to MACE, a composite of first events of cardiovascular death, acute coronary syndrome including myocardial infarction, and ischemic stroke.
Cox regression models assessed the association between categorized index eGFR and time to each MACE outcome, with follow-up beginning from date of index eGFR. Analysis used separate models for each age group to estimate hazard ratios relative to age-specific reference eGFR categories with adjustments for sex, income, residence location, comorbidities, and other variables.
Approximately 4.4 million (51%) participants had two or more index eGFR measures, and 746,948 (9%) had an albumin-to-creatinine ratio measure within 1 year of index.
Prevalence of eGFR below age-specific referents at index was 17.3% for those aged 18-39 years, 18.7% for those patients aged 40-49 years, and 17.1% for those aged 50-65 years.
The 18-39 years-old subgroup had 42,372 MACE events during follow-up, the 40-49 years-old subgroup had 102,039 MACE events, and the oldest subgroup had 342,197 MACE events.
Adjusted hazard ratios for MACE events (and for MACE plus heart failure events) were highest, although crude incidence rates were lowest, in the 18-39 years-old subgroup. For example, those 18-39 years old with an eGFR of 70-79 mL/min/1.73 m2 had a significant 31% increased rate of MACE events compared with similarly aged people in the study with an eGFR that fell within the reference range for this age group (100-109 mL/min/1.73 m2). Those 40-49 years old with an eGFR of 70-79 mL/min/1.73 m2 had an adjusted hazard ratio for MACE events that was 9% above the reference range for this age stratum, and those 50-65 years old in this eGFR range had an adjusted hazard ratio 7% above the reference group.
Findings suggest that eGFR values above the current definition of advanced-stage chronic kidney disease (eGFR below 60 mL/min/1.73 m2) but below age-specific mean values are an important, underrecognized marker for elevated cardiovascular disease risk and that subclinical eGFR declines to less than 100 mL/min/1.73 m2 in young adults link to a significant cardiovascular risk.
An editorial accompanying the report called it a “landmark,” and concluded that evidence now exists “to support that routine screening for eGFR and urinary albumin excretion in people as young as 18 years old with very low or low risk is generally helpful, as it can offer effective early support to young adults who are at risk of future poor clinical outcomes.”
The study was published online today in the Journal of the American College of Cardiology by researchers at the Ottawa Hospital, the University of Ottawa, the University of Calgary, and the University of Manitoba, all in Canada. The accompanying editorial was written by two researchers from the University of Minnesota in Minneapolis.
The study used ICD-10 diagnostic codes to define the endpoints and the outcomes were not adjudicated by an external committee, allowing for potential misclassifications.
Residual confounding and alternative explanations for observed associations are possible, but the cohort’s large size and consistency across additional analyses and the preexisting literature strengthen the findings. Some data were missing for income and residence location but these gaps were uncommon and there were no gaps in the data on exposure or outcomes.
The findings did not provide insight into the mechanism of eGFR reduction, nor the risk of a particular etiology or subtype of CV outcome. Only some of the cohort had repeated measures of eGFR, albumin-to-creatinine ratio, or both.
The study received no commercial funding. The study’s corresponding author, Manish Sood, MD, has been a consultant to AstraZeneca, Bayer, Otsuka, and GlaxoSmithKline. Most of the co-authors had no disclosures. Full disclosure information is available with the original article. Neither of the editorialists had relevant disclosures.
Mitchel L. Zoler is a reporter with Medscape and MDedge based in the Philadelphia region. @mitchelzoler
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