Measured GFR Validates CKD Threshold and Predicts Adverse Outcomes: JAMA
Sweden: A large Swedish study found that lower measured glomerular filtration rate (mGFR) was associated with increased risks of all-cause mortality, kidney failure requiring replacement therapy, heart failure hospitalization, acute kidney injury, and major adverse cardiovascular events.
An mGFR of 60 mL/min/1.73 m² was linked to substantially worse outcomes than an mGFR of 90 mL/min/1.73 m², supporting the current CKD diagnostic threshold of 60 mL/min/1.73 m². Among estimated GFR methods, eGFR based on both creatinine and cystatin C (eGFRcr-cys) most accurately reflected mortality risk, while creatinine-only eGFR underestimated risk and cystatin C–only eGFR overestimated it.
The findings were published in JAMA by Edouard L. Fu from the Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden, and colleagues.
Glomerular filtration rate (GFR) is a key indicator of kidney function, but the relationship between directly measured GFR (mGFR) and long-term health outcomes is not fully understood. To investigate this, researchers examined the association between mGFR and adverse clinical outcomes and compared its performance with commonly used estimated GFR (eGFR) equations.
The retrospective cohort study included 6,174 adults in Stockholm, Sweden, from 2011 to 2021. Measured GFR was assessed using iohexol plasma clearance, while eGFR was calculated using creatinine alone, cystatin C alone, and a combined creatinine-cystatin C equation. Participants were followed for a median of 5.9 years.
The median age was 59 years, 60% of participants were men, and during follow-up, 1,977 participants died while 426 progressed to kidney failure requiring replacement therapy.
The study reported the following findings:
- A lower measured glomerular filtration rate was associated with a higher risk of adverse health outcomes.
- An mGFR of 60 mL/min/1.73 m² was linked to higher all-cause mortality rates than an mGFR of 90 mL/min/1.73 m² (27.6 vs 22.4 per 1,000 person-years).
- An mGFR of 60 mL/min/1.73 m² was associated with a 21% higher risk of all-cause mortality (HR 1.21).
- The rate of kidney failure requiring replacement therapy was higher at an mGFR of 60 mL/min/1.73 m² than at 90 mL/min/1.73 m² (1.2 vs 0.4 per 1,000 person-years).
- An mGFR of 60 mL/min/1.73 m² was associated with nearly a threefold higher risk of kidney failure requiring replacement therapy (HR 2.85).
- Lower mGFR was also associated with increased risks of heart failure hospitalization, acute kidney injury, and major adverse cardiovascular events.
- Among estimated GFR methods, eGFR based on both creatinine and cystatin C (eGFRcr-cys) most closely matched the mortality risk observed with measured GFR.
- Creatinine-based eGFR underestimates mortality risk.
- Cystatin C–based eGFR overestimated mortality risk.
The findings highlight declining kidney function as a strong predictor of mortality, kidney failure, and cardiovascular complications.
The researchers noted limitations, including potential variability in mGFR measurements, specialist-driven patient selection, limited generalizability beyond Stockholm, insufficient power for albuminuria subgroup analyses, and the absence of race-related data.
Overall, the results support the current CKD diagnostic threshold of 60 mL/min/1.73 m² and indicate that eGFR based on both creatinine and cystatin C (eGFRcr-cys) most closely reflects mortality risk when direct GFR measurement is not available.
Reference:
Fu EL, Créon A, Grams ME, et al. Measured and Estimated Glomerular Filtration Rates and Risk of Adverse Health Outcomes. JAMA. Published online June 04, 2026. doi:10.1001/jama.2026.9639
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