In Stockholm, 6,174 adults held a quiet key to solving a decades-old medical puzzle: whether the thresholds doctors use to diagnose kidney disease actually predict who will get sicker. Now, researchers from Karolinska Institutet and Leiden University Medical Center have confirmed they do—and they've found a way to predict risk even more accurately.
Chronic kidney disease silently affects between 10 and 14 percent of adults worldwide, yet it often goes undetected until significant damage has occurred. The challenge is that doctors cannot easily measure kidney function directly; instead, they rely on blood tests to estimate how well the kidneys are filtering waste. These estimates have long been used to stage the disease and guide treatment decisions, but a nagging question persisted: were those diagnostic cutoffs truly reflecting the actual health risks, or were they simply statistical associations obscured by other factors like muscle mass, inflammation, and body weight?
To answer this question, Juan-Jesus Carrero, a professor at Karolinska Institutet's Department of Medical Epidemiology and Biostatistics, and his team studied adults who underwent iohexol clearance testing—a precise measurement of kidney function involving injected contrast agents tracked over time. Between 2011 and 2021, these 6,174 participants were followed for nearly six years while researchers tracked serious health outcomes: death, kidney failure, heart failure, acute kidney injury, and cardiovascular disease.
The findings, published in JAMA in 2026, were striking. Lower measured kidney function was associated with progressively higher risk across every outcome examined. Consider the specific threshold currently used to diagnose moderate-to-severe chronic kidney disease: a glomerular filtration rate of 60 ml/min/1.73m². Adults at this level faced a 21 percent higher risk of death and nearly three times the risk of kidney failure compared to those with a filtration rate of 90.
Beyond confirming that existing diagnostic thresholds reflect real danger, the research revealed an actionable improvement to clinical practice. When doctors combined two routine blood tests—creatinine and cystatin C—they achieved the most accurate risk assessment for mortality. Neither test alone captured the full picture; together, they provided what Carrero describes as "a more reliable picture of patient risk than with either test alone."
This matters profoundly. Chronic kidney disease progresses silently, often without symptoms until substantial kidney function has been lost. Early detection and intervention can slow progression and prevent the cascade of complications that follow. By validating that the established diagnostic framework identifies patients truly at risk, this research provides clinicians with scientific confirmation that the effort invested in screening, diagnosing, and treating kidney disease saves lives.
"By confirming that the clinical framework for CKD care truly identifies patients at higher risk of adverse outcomes, we hope clinicians renew their emphasis on screening, diagnosing and treating this disease," Carrero said. The message is clear: the thresholds that seemed arbitrary to some are, in fact, anchored in measurable harm. And the simple act of ordering two blood tests instead of one can refine that clarity further, helping doctors protect their patients before kidney disease becomes irreversible.