Editorial: The evolution of glomerular filtration rate estimation: Embracing the new EKFC equation

Abstract

Addressing the accurate staging of chronic kidney disease (CKD) represents a formidable challenge worldwide, resonating deeply within Ukraine's healthcare landscape. The intricacies of estimating CKD stages often result in the dilemma of its under- or overestimation, magnifying the urgency for precise assessment methods [1, 2]. The estimation of glomerular filtration rate (GFR) is a cornerstone in the assessment of kidney function, guiding diagnosis, management, and therapeutic decisions in patients with kidney disease. Traditional approaches, such as the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, though widely utilized, grapple with inherent limitations, potentially compromising diagnostic accuracy [3]. To confront this critical issue, the European Kidney Function Consortium (EKFC) has introduced new equations for GFR estimation using both creatinine and cystatin C, which promise to enhance the precision and applicability of kidney function assessment. Moreover, a recent KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease has recommended using the combination of creatinine and cystatin C (creatinine and cystatin C–based estimated glomerular filtration rate [eGFRcr-cys]) for assessment GFR category (1B) [4]. However, the successful integration of the EKFC equation into clinical practice necessitates widespread awareness and adoption among healthcare professionals. This editorial aims to introduce the Ukrainian nephrology community, as well as a broad readership of the journal, to this innovative approach to kidney health assessment. The limitations of creatinine-based GFR estimation. Serum creatinine, a byproduct of muscle metabolism, has been the backbone of GFR estimation for decades. However, its utility is marred by significant limitations. Creatinine production varies with muscle mass, diet, and other physiological processes, leading to inaccuracies in GFR estimation, especially in individuals with atypical body compositions or dietary habits [5, 6]. Creatinine-based GFR estimation can also be less accurate in specific populations, such as the elderly, individuals with extreme body compositions, and those with acute kidney injury [3]. In these cases, the equations may not accurately reflect kidney function, leading to potential misclassification of CKD stages. Moreover, creatinine clearance exceeds GFR because creatinine is not only filtered by the glomeruli but also secreted by the proximal tubule. This can lead to an overestimation of GFR. Conversely, in conditions where muscle mass is reduced, such as in elderly or malnourished individuals, GFR may be underestimated [3, 5]. Lastly, some medications can inhibit tubular secretion of creatinine, thereby increasing serum creatinine levels without a corresponding decrease in GFR, leading to an overestimation of CKD severity [7]. The role of cystatin C in enhancing GFR estimation. Cystatin C, a low molecular weight protein produced at a constant rate by all nucleated cells, offers a promising alternative or complementary biomarker for GFR estimation [8]. One of the key advantages of cystatin C is its independence from muscle mass, making it particularly valuable in populations where muscle mass may vary significantly, such as the elderly, individuals with malnutrition, or those with muscle wasting conditions [9]. This independence from muscle mass confers cystatin C with greater accuracy in estimating GFR, especially in patients with early-stage kidney disease where changes in muscle mass may not yet significantly affect creatinine levels [8, 9].  Studies have demonstrated that cystatin C has a higher diagnostic sensitivity for abnormal GFR compared to creatinine [10]. This means that cystatin C is more likely to identify patients with reduced kidney function. Introducing the EKFC equation. The EKFC has developed a new equation that incorporates both serum creatinine and cystatin C levels, aiming to overcome the limitations of previous formulas. This innovative approach is grounded in extensive research and validation across various populations [11–13]. The EKFC equation is race- and sex-free, addressing ethical concerns associated with previous equations and promoting a more inclusive and equitable assessment of kidney function. By combining both markers, the EKFC equation offers a more reliable estimate of GFR, particularly in individuals where discrepancies between creatinine-based and cystatin C-based estimates exist. This approach aligns with the principles of personalized medicine, emphasizing tailored healthcare interventions based on individual patient characteristics. However, the successful integration of the EKFC equation into clinical practice requires widespread awareness and adoption among healthcare professionals. To facilitate this, the EKFC has made a calculator available online at ekfccalculator.pages.dev, and there are ongoing efforts to develop additional tools to improve the implementation of these equations. These tools are crucial for enabling healthcare providers to easily apply the EKFC equation in their clinical practice, ensuring that patients benefit from the most accurate and equitable assessment of kidney function available. In conclusion, the development of the EKFC equation marks a pivotal moment in the evolution of GFR estimation. As the medical community continues to embrace the EKFC equation, it is crucial to familiarize healthcare providers with its application and implications. We sincerely believe that the evidence, as outlined above, and this editorial support the widespread adoption of the EKFC eGFR equations in Ukraine.