Impact of GDMT implementation on albuminuria in HFrEF

Background Heart failure with reduced ejection fraction (HFrEF) and chronic kidney disease (CKD) are closely linked. Albuminuria is an independent risk marker for worse outcomes in both diseases. While guideline-directed medical therapy (GDMT) often leads to an initial, acceptable rise in serum creatinine, it helps stabilize kidney function over time. However, the effects of GDMT on albuminuria vary. The dynamics of estimated glomerular filtration rate (eGFR) and albuminuria during dedicated GDMT up-titration remains poorly characterized. Purpose This study aimed to assess the impact of GDMT up-titration on eGFR and albuminuria in patients with HFrEF over the course of one year. Methods A total of 247 patients with HFrEF with complete baseline (BL), i.e. first presentation, and 1-year follow-up data were included from our outpatient HFrEF registry. Patient characteristics, medications and laboratory parameters were documented. Patients were categorized according to the 2024 KDIGO CKD classification based on eGFR and urine albumin-creatinine ratio (UACR). Changes in eGFR and UACR were analyzed during GDMT up-titration. Results Up-titration of HF medications was successful; target doses (TDs) of all recommended HF medications increased significantly during follow-up (BL vs 1-year, p<0.001 for all) whereas the majority of patients received ≥50% of the recommended TDs at 1-year (86% for BB, 89% for RASi and 89% for MRA) (Figure 1A). GDMT implementation was accompanied by a significant decrease in NT-proBNP (BL vs 1-year: 1968 [702-5014] vs 882 [234-3083] pg/ml, p<0.001) and an increase in renin (BL vs 1-year: 163 [30-673] vs 194 [37-751] µlU/ml, p=0.012). Overall, eGFR but also UACR decreased significantly (eGFR: BL vs 1-year: 59 [39-74] vs 56 [35-73] ml/min/1.73m2, p=0.003; UACR: BL vs 1-year: 29 [12-101] vs 25 [10-75] mg/g, p=0.011) (Figure 1B). Figure 2 depicts the estimated risk categories and changes of eGFR and UACR according to the CKD categories. A decrease in eGFR was most evident in the subgroup of patients with high eGFR (p=0.001 for G1 and p=0.007 for G2) or mild albuminuria, while an improvement in albuminuria was observed for both moderate and severe albuminuria (p=0.032 for A2 and p<0.001 for A3) and worse eGFR (Figure 2B). With the combination of effects patient´s risk categories according to the KDIGO 2024 classification did not change significantly after the implementation of GDMT (Figure 2A). Conclusions GDMT implementation in HFrEF results in a decline in eGFR alongside an improvement in UACR. The eGFR reduction is most pronounced in patients with mild CKD, while albuminuria improves in both moderate and severe albuminuria. However, these combined effects do not lead to a lower KDIGO risk classification. The effect on kidney and cardiovascular outcomes needs to be assessed for subgroups.