A Comparison of the 2009 CKD-EPI and EKFC Equations for Estimating GFR in a Large Italian Outpatient Cohort, and the Potential Consequences for Patients’ Management

IntroductionAn accurate estimation of the glomerular filtration rate (eGFR) is essential for chronic kidney disease (CKD)management and clinical decision-making. The CKD-EPI 2009 has long been the standard but it is currently beingreplaced by new equations designed to correct some of its shortcomings. Specifically, in 2021 the European KidneyFunction Consortium (EKFC) developed a full age spectrum equation aimed at improving accuracy by introducing agespecificparameters. Unlike the CKD-EPI equation, which applies a single fixed age coefficient, the EKFC equationtheory supports a non-linear decline of kidney function, where GFR remains quite stable until 40 years of age beforeprogressively decreasing with ageing.ObjectivesTo understand how eGFR estimates obtained by CKD-EPI and EKFC differ according to age and sex, and to assess theimpact of CKD categories reclassification and subsequent clinical decision making induced by shifting from the CKD-EPI2009 to the EKFC equation.MethodsData were retrospectively collected from the Emilia-Romagna regional PIRP registry of individuals with chronic kidneydisease, which was established in 2004 and includes data from patients attending the 12 hospital nephrology units of theregion. For this analysis, we selected patients who entered PIRP from 2009 onwards and medical records with creatininerange 0.45-5.54 mg/dl to ensure compatibility with creatinine calibration methods used by EKFC. After excluding recordswith known data quality issues, we obtained a cohort of 127,876 medical records from 30,549 patients. Calculated eGFRwas grouped into categories (G1 to G5) according to the KDIGO CKD guidelines. Statistical analyses were alldescriptive and included gender-specific scatterplots to compare the delta between formulae (CKD-EPI - EKFC) andpatients’ age.ResultsThe EKFC equation provided lower eGFR estimates than CKD-EPI in 80.7% of records. This was particularly evident inyounger and older age groups, while higher estimates from EKFC concentrated around 40 years of age. Groupingaccording to the baseline eGFR placed 87.9% of patients in the same category. EKFC estimation using baseline dataclassified 254 patients (0.8%) in a less advanced CKD group and 3418 patients (11.2%) in a more advanced CKD group.Dialysis initiation was disproportionately lower (2.5% vs. 8.9% overall) and higher (36.2%) in patients assigned to a moreor less advanced CKD group by EKFC, respectively. Deaths were disproportionately lower when EKFC assignedpatients to a less advanced CKD group (10.2% vs. 30.6% overall).ConclusionsConsistent with previous literature, our results showed that EKFC equation tend to attribute lower eGFR values thanCKD-EPI equation. However, this was not uniformly distributed across all age brackets, due to the age dependency ofGFR hypothesized in the EKFC equation. For 10% of patients, switching to the EKFC estimate would have resulted in achange of CKD grouping, which could have impacted disease management. Assuming that the hypothesis of age-GFRrelationship made in EKFC is more accurate than that underlying CKD-EPI, this figure indicates that in absolute terms agreat number of patients would benefit from the switch. Nevertheless, the observed discrepancies in clinical outcomeswarrant careful further investigation.