Effect of GDMT optimization on KDIGO risk categories in HFrEF

Background

Heart failure with reduced ejection fraction (HFrEF) often coexists with chronic kidney disease (CKD). While changes in estimated glomerular filtration rate (eGFR) are monitored during up-titration of guideline-directed medical therapy (GDMT), the added value of urine albumin-to-creatinine ratio (UACR) and the Kidney Disease: Improving Global Outcomes (KDIGO) risk categories remains less studied.

Purpose

To evaluate changes in eGFR, UACR, and KDIGO risk categories during GDMT up-titration in HFrEF and their association with renal and HF outcomes.

Methods

We analyzed 234 HFrEF outpatients from a tertiary care center with baseline and 12-month follow-up. The association of KDIGO trajectories with adverse renal and HF outcomes was evaluated by Kaplan–Meier analyses.

Results

Over 12 months, GDMT was intensified, with most patients achieving ≥50% of target doses. eGFR declined significantly (60 to 56 mL/min/1.73m²; p=0.007), whereas UACR improved (31 to 24 mg/g; p=0.003). 55.6, 23.9 and 20.5% of patients showed stable, worsening or improved KDIGO trajectory. UACR was the sole responsible biomarker for KDIGO reclassification in 35% of cases (Figure 1).

Event rates increased stepwise across baseline KDIGO risk classes [renal events: 4% vs 12% vs 15% vs 27%, p<0.001 for trend; HF hospitalization or death 19% vs 29% vs 37% vs 56%, p<0.001 for trend, 2-years estimate, respectively]. Similarly, improving, stable, and worsening KDIGO trajectories were associated with progressively worse outcomes [renal events: 6% vs 15% vs 21%, p=0.034 for trend; HF hospitalization or death: 11% vs 43% vs 46%; p=0.007 for trend, 2-year estimate, respectively] (Figure 2).

Conclusions

There is a considerable variability in KDIGO-risk trajectories upon GDMT optimization in

HFrEF. UACR provides complementary information beyond eGFR and improves risk

stratification for renal and HF outcomes.Figure 1.KDIGO during GDMTFor image description, please refer to the figure legend and surrounding text.Figure 2.KDIGO and outcomesFor image description, please refer to the figure legend and surrounding text.