Implications of the 2021 CKD-EPI cystatin C/creatinine eGFR equation for eligibility for therapy in HFrEF: insights from PARADIGM-HF

Estimated glomerular filtration rate (eGFR) is a key determinant of eligibility for many life-saving therapies in HFrEF. Recently, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) provided new equations based on creatinine (CKD-EPIcr), cystatin C (CKD-EPIcys) or both (CKD-EPIcyscr) that do not include race. These new equations may reclassify individuals, irrespective of race, from one eGFR category to another, with implications for eligibility for HFrEF treatments.

To assess the difference between eGFR estimation using the 2021 CKD-EPIcyscr equation and the 2009 CKD-EPIcr and Modification of Diet in Renal Disease Study (MDRD)-4 equations which are still standard in many European laboratories.

We included patients from PARADIGM-HF with cystatin C and creatinine values available at the time of randomization. For each patient, baseline eGFRs were calculated using the 3 equations described. Our focus was on patients with chronic kidney disease (CKD) stages III–V.

Overall, 1910 patients were eligible. Mean age was 67.3 (10.1) year and 385 (18.7%) were female. Using 2009 CKD-EPIcr, 779 patients were in CKD stages 3–5, of which 233 (30%) were reclassified to a better CKD stage (higher eGFR) with the 2021 CKD-EPIcyscr equation (Table 1). Similar reclassification was seen when comparing MDRD-4 with the 2021 CKD-EPIcyscr equation: 277 (33%) of 831 patients in CKD stages 3–5 were reclassified to a better CKD stage (Figure 1).

The 2021 CKD-EPIcyscr equation favourably reclassified CKD stage in a large percentage of patients with HFrEF and a low eGFR, potentially increasing the proportion of these patients considered eligible for guideline-recommended therapies.

Type of funding sources: None.