The kidney function thresholds currently used to diagnose chronic kidney disease reflect an actual increase in the risk of serious disease, according to 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 (CKD) affects approximately 10–14 percent of the adult population globally. Because direct measurement of kidney function, i.e. measured glomerular filtration rate (mGFR), is rarely available, doctors 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 renal function (such as muscle mass, inflammation, and obesity), raising questions about whether these thresholds reflect the risk attributable to renal impairment per se. The aim of the new study was therefore to investigate whether the established diagnostic framework for CKD corresponds to a true increase in risk when renal function is measured directly.

Examined how efficient the kidneys were

The study includes 6,174 adults in Stockholm who underwent mGFR determination using the iohexol clearance test, where a contrast agent is injected and tracked over time to measure how effectively the kidneys filter the blood, between 2011 and 2021. The participants were then followed for almost 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 a higher risk of all outcomes. For example, an mGFR of 60 mL/min/1.73 m2 ^, a threshold that diagnoses moderate to severe CKD, was associated with a 21 percent higher risk of death and a nearly three-fold higher risk of kidney failure compared with 90 mL/min/1.73 ^m2 .

“By confirming that the clinical framework for CKD care does indeed identify patients at higher risk of adverse outcomes, we hope that clinicians will once again place greater emphasis on screening, diagnosis and treatment of this disease,” says Juan-Jesus Carrero , professor at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, and the 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 therefore provides a more reliable picture of the patient’s risk than using only one test, which suggests that they should be used together in clinical decisions, says Juan-Jesus Carrero.

See the study for information about research funders and possible conflicts of interest.

Publication

“Measured and estimated glomerular filtration rates and risk of adverse health outcomes”, Edouard L. Fu, Antoine Créon, Morgan E. Grams, Josef Coresh, Arvid Sjölander, Anne-Laure Faucon, Michelle M. Estrella, Friedo W. Dekker, Michael G. Shlipak, Lesley A. Inker, Andrew S. Levey, Juan-Jesus Carrero, JAMA , online 4 June 2026, doi: 10.1001/jama.2026.9639.

Source https://ki.se/