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Creatinine-Cystatin C eGFR More Accurately Predicts Outcomes in Older Patients With CKD – Renal and Urology News

Estimated glomerular filtration rate (GFR) based on both creatinine and cystatin C (eGFRcr-cys) more accurately predicts adverse outcomes in older adults compared with creatinine-based eGFR (eGFRcr) alone, a new study finds.

Current guidelines define a GFR less than 60 ml/min/1.73 m2 for 3 months as moderate to severe chronic kidney disease (CKD), even without albuminuria criteria. That threshold has been associated with greater risks of kidney failure, all-cause mortality, and other outcomes. eGFRcr is usually used in routine clinical practice.

Using concurrent eGFRcr and eGFRcr-cys data from a Swedish cohort of 82,154 real-world patients aged 65 years or older, investigators assessed 8 outcomes, including all-cause mortality, cardiovascular mortality, kidney failure requiring replacement therapy (KFRT), all-cause hospitalization, hospitalization with infection, myocardial infarction or stroke, heart failure, and acute kidney injury (AKI).

Using eGFRcr-cys rather than eGFRcr reclassified 31.2% older adults, predominantly to a more severe GFR category, Shoshana H. Ballew, PhD, of New York University Grossman School of Medicine in New York, New York, and colleagues reported in the Annals of Internal Medicine.

“Compared with low eGFRcr in older patients, low eGFRcr-cys was more strongly associated with adverse outcomes and the associations were more uniform [and biologically plausible],” they wrote. The associations between eGFRcr and outcomes, by contrast, were U-shaped.

For example, at an eGFR of 60 vs 80 mL/min/1.73m2, eGFRcr failed to reveal increased death risks. The risks for all-cause mortality were increased 1.0- and 1.2-fold using eGFRcr and eGFRcr-cys, respectively. For cardiovascular mortality, those risks were increased 1.0- and 1.3-fold, respectively.

KFRT risks were 1.4- and 2.6-fold higher and AKI risks were 1.6- and 2.3-fold higher at an eGFR of 60 vs 80 mL/min/1.73m2 using eGFRcr and eGFRcr-cys, respectively. Heart failure risks were 1.2- and 1.5-fold higher, respectively.

Absolute incidence rates for all outcomes progressively increased with lower eGFRcr-cys categories. For example, rates of recurrent hospitalizations at age 70 years were 39, 44, and 65 per 100 person-years at eGFRcr-cys levels of 80, 60, and 30 mL/min/1.73 m2, respectively. Rates of myocardial infarction or stroke at the same age were 2.0, 2.6, and 4.8 per 100 person-years, respectively. Rates of heart failure were 3.2, 5.6, and 15.0 per 100 person-years, respectively.

Using an eGFRcr value of 80 mL/min/1.73m2 rather than eGFRcr-cys likely captures more older adults with low muscle mass and poor health status, the investigators noted.

“The broad range of risks associated with CKD at older age is better appreciated when cystatin C is included in GFR estimation,” Dr Ballew’s team concluded.

The findings are in step with a proposed age-adapted classification of CKD.

Among the study’s limitations, the investigators were unable to adjust for muscle mass, diet, obesity status or body mass index, smoking, and inflammation. Although it is the most accurate, measured GFR was not available.

In an accompanying editorial, Georges N. Nakhoul, MD, MEd, and Crystal A. Gadegbeku, MD, of Cleveland Clinic Health System, Department of Kidney Medicine, in Cleveland, Ohio commented:

“The significance of this study is that it sheds light on the possibility that we are measuring more than kidney function with CKD staging. As we have more tools in the toolbox to consider management within the framework of cardiovascular-kidney-metabolic syndrome, it is timely to gain insight on the appropriate use of kidney biomarkers in what is likely multisystemic disease, particularly in the aging population.”


Fu EL, Carrero JJ, Sang Y, et al. Association of low glomerular filtration rate with adverse outcomes at older age in a large population with routinely measured cystatin C. Ann Intern Med. Published online January 30, 2024. doi:10.7326/M23-1138

Nakhoul GN and Gadegbeku CA. Glomerular filtration estimating equations and clinical outcomes: What are we measuring? Ann Intern Med. Published online January 30, 2024. doi:10.7326/M23-1138