Current chronic kidney disease diagnostic thresholds reflect true patient risk

The thresholds for kidney function currently used to diagnose chronic kidney disease (CKD) reflect a true increase in the risk of serious illness. This is shown by a study from Karolinska Institutet and Leiden University Medical Center published in the journal JAMA. The researchers also show that risk assessment becomes more accurate when two common blood tests, creatinine and cystatin C, are combined to estimate kidney function.

Chronic kidney disease affects about 10-14 percent of the adult population globally. Because direct measurement of kidney function, i.e. measured glomerular filtration rate, (mGFR), is rarely available, clinicians rely on blood tests to estimate it as estimated glomerular filtration rate (eGFR).

Current diagnostic thresholds and staging are based on associations between eGFR and adverse outcomes. However, serum creatinine and cystatin C are influenced by factors other than kidney function (such as muscle mass, inflammation, and obesity), raising questions about whether these thresholds reflect risk attributable to reduced kidney function itself.

The rationale behind the new study was therefore to investigate whether the established diagnostic framework for CKD corresponds to a true increase in risk when kidney function is measured directly.

The study includes 6,174 adults in Stockholm who, between 2011 and 2021, underwent mGFR determination using iohexol clearance testing, where a contrast agent is injected and tracked over time to measure how effectively the kidneys filter the blood. The participants were then followed for nearly six years to assess the risk of, among other things, death, kidney failure, heart failure, acute kidney injury, and cardiovascular disease.

The researchers found that lower mGFR was associated with progressively higher risk across all outcomes. For example, a mGFR of 60 ml/min/1.73m², a threshold that diagnoses moderate-to-severe CKD, was associated with a 21 percent higher risk of death and nearly threefold higher risk of kidney failure compared with 90 ml/min/1.73m².

By confirming that the clinical framework for CKD care truly identifies patients at higher risk of adverse outcomes, we hope clinicians renew their emphasis in screening, diagnosing and treating this disease." 

Juan-Jesus Carrero, Professor, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, and study's corresponding author

The researchers also compared mGFR with eGFR equations used in routine clinical practice. The most accurate risk assessment for mortality was achieved when eGFR was calculated using both creatinine and cystatin C.

"Using both blood tests thus provides a more reliable picture of patient risk than with either test alone, supporting their combined use in clinical-decision making"," says Juan-Jesus Carrero.