Modest reductions in kidney function are associated with a heightened risk for adverse events, especially among younger adults, according to new research.
In a retrospective, population-based cohort study that included almost 9 million participants, modest reductions in estimated glomerular filtration rate (eGFR) were associated with a 42% increased risk of all-cause mortality, cardiovascular events, and kidney failure among adults younger than 40 years, compared with older adults.
The increased risk “is quite clear, it’s across the board, and it starts roughly as you get above 20% to 25% below what normal should be,” senior author Manish M. Sood, MD, professor of medicine at the University of Ottawa and senior scientist at the Ottawa Hospital in Ontario, Canada, told Medscape Medical News. “If we want to prevent future kidney disease, if we want to prevent heart disease, we have to pay attention to these slight decreases in kidney function in young people.”
The findings were published June 23 in The BMJ.
Serum Creatinine Measurements
Kidney function is high during youth and decreases with age. For patients of any age without albuminuria, the current threshold for chronic kidney disease (CKD) is an eGFR of <60 mL/min/1.73 m2 for at least 90 days. Using this threshold, the kidney function of a younger adult would have to be reduced by half to be diagnosed with CKD, said Sood.
Previous studies have suggested that early sustained reductions in eGFR among adults younger than 40 years are linked to premature cardiovascular disease. But those studies were too small to show definitively that adverse outcomes are linked to reduced kidney function in this age group.
The investigators examined healthcare administrative databases from the Institute for Clinical and Evaluative Sciences to obtain data on demographics, vital statistics, healthcare encounters, and laboratory tests for 8,703,871 adults in Ontario. All had at least one outpatient serum creatinine measurement. No participant had a history of kidney disease. The study spanned the period from January 1, 2008, to March 31, 2020.
The researchers categorized index serum creatinine measurements into 10-unit increments from 50 mL/min/1.73 m2 to >120 mL/min/1.73 m2. They also stratified the cohort by age, creating groups of participants aged 18–39 years, 40–49 years, and 50–65 years. The investigators stratified participants according to the following age-specific eGFR referents: 100–110 mL/min/1.73 m2 for those aged 18–39 years, 90–100 mL/min/1.73 m2 for those aged 40–49 years, and 80–90 mL/min/1.73 m2 for those aged 50–65 years.
The main study outcome was a composite of all-cause mortality, any cardiovascular outcome, or kidney failure, which was defined as initiation of dialysis or receipt of a kidney transplant.
New Research Area
The mean age of the participants was 41.3 years. The mean index eGFR was 104.2 mL/min/1.73 m2. The median follow-up duration was 9.2 years.
Modestly reduced eGFR measurements specific to age were recorded for 18.0% of participants aged 18–39 years, 18.8% of participants aged 40–49 years, and 17.0% of participants aged 50–65 years.
The younger patients were at greater risk for adverse outcomes, compared with patients in the two other older age groups. For modest reductions (defined as eGFR 70–80 mL/min/1.73 m2), the hazard ratio (HR) of adverse outcomes for those aged 18–39 years was 1.42. The HR was 1.13 for those aged 40–49 years and 1.08 for those aged 50–65 years.
“No matter what we did, we looked at it in so many ways, and the risk was always there,” said Sood. “Our study was huge, and we really looked in detail, by little increments of 10%, at young people and found this increased risk.”
The findings will open up a new area of research, said Sood. “What do we do for these people? We don’t know. It’s reasonable to at least monitor them more closely and to advise them to adopt a healthy lifestyle, not to start cigarette smoking, stay slim, eat well, exercise, all things we know reduce cardiovascular risk.”
Once CKD develops, it’s rarely reversible, Sood added. “CKD is progressive. So, the goal here is to see if we can prevent the onset of more advanced kidney disease. The number one killer of people with kidney disease is actually premature heart disease,” he said.
“Be Aware”
Commenting on this study for Medscape, Jia Hwei Ng, MD, assistant professor of medicine at Northwell/Hofstra University in Hempstead, New York, agreed that it cannot be good for patients when test results are normal and kidney function is modestly reduced.
“The test will come back in the normal range, but if their kidney function is lower than expected, this means that we are delaying detection. And that means we are not seeing them sooner, we are not checking them as often, and this could lead to worse kidney function. So, we are missing the boat,” Ng said. She did not participate in the study.
Kidney function will never return to normal, and the emphasis must be on preserving as much of it as possible, added Ng.
“The kidney is like a gas tank. We are born with a full gas tank, and it empties throughout life, and you never get to fill it up again. So, the medication we use for kidney disease is aimed at slowing down its progression, so that when you’re 80 years old, you will still have some kidney function and won’t need dialysis. This study reminds us to be aware and monitor our patients,” said Ng.
The study was supported by the Institute of Clinical Evaluative Sciences, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care. Sood reported no relevant financial relationships. Ng reported a financial relationship with Vifor Pharmaceuticals. She is the founder of PublishedMD Consulting.
BMJ. Published June 23, 2023. Full text
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