Performance of new and panel CKD‐EPI equations in European adults with type 2 diabetes

Chronic kidney disease (CKD) is a common complication of type 2 diabetes (T2D) characterized by albuminuria and a progressive decline in the glomerular filtration rate (GFR).1 CKD in the setting of T2D can be the result of diabetic nephropathy, non-diabetic renal disease, or a combination of these factors.2 Regardless of the aetiology, early diagnosis of CKD enables interventions to slow GFR decline, including the discontinuation of nephrotoxic medications and the initiation of renoprotective medications.3, 4 Reduced GFR also necessitates dose adjustments for renally excreted medications, including several antidiabetic agents.5 Improper dose adjustment can lead to adverse drug reactions, which are a common but largely preventable cause of hospitalization.6 Therefore, accurate GFR assessment is crucial for effective diagnosis and management of CKD in people with T2D. Kidney Disease Improving Global Outcomes (KDIGO) guidelines from 2012 recommend using estimated GFR (eGFR) equations based on creatinine and/or cystatin C for evaluation and management of CKD.7 Creatinine is the least expensive option and the biomarker of choice in most clinical settings. Cystatin C is less common, but some clinical settings (notably Sweden) have incorporated it into routine care. The main limitation of these endogenous filtration markers is that their concentration is influenced by factors other than kidney function. As these ‘non-renal factors’ are unique to each filtration marker, combining multiple markers in a single equation reduces the influence of non-renal factors. Unsurprisingly, eGFR equations that combine creatinine and cystatin C have been shown to outperform equations based on either filtration marker alone in the general population,8 although this may not be true for people with T2D.9 The most common eGFR equations in clinical practice are those developed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). The original CKD-EPI equations based on creatinine (2009 CKD-EPIcre), cystatin C (2012 CKD-EPIcys), or their combination (2012 CKD-EPIcomb) have largely replaced alternative equations in both the United States and Europe.10, 11 In response to criticisms of including race as a variable, the CKD-EPI group revised their equations to exclude race, yielding 2021 CKD-EPIcre and 2021 CKD-EPIcomb.12 Similarly, the 2012 CKD-EPIcys equation was revised to exclude sex as a variable, yielding 2023 CKD-EPIcys.13 National renal societies in the United States now recommend 2021 CKD-EPIcre and 2021 CKD-EPIcomb over their earlier counterparts.14 However, there is an ongoing debate about whether this recommendation is appropriate for European populations, and most clinical settings in Europe continue to use 2009 CKD-EPIcre. Given the apparent success of combining creatinine and cystatin C, it has been suggested that incorporating additional filtration markers could further reduce the impact of non-renal factors. In 2020, the CKD-EPI group developed an equation based on a panel of filtration markers (2020 CKD-EPIpanel), which includes creatinine, cystatin C, β-trace protein (BTP) and β2-microglobulin (B2M).15 Importantly, the authors found that the inclusion of BTP and B2M resulted in strong performance across patient subgroups without the explicit inclusion of race. The purpose of the present study was to compare the performance of these different CKD-EPI equations to identify the most accurate equation(s) among European adults with T2D.