Heart Failure Therapies and Renal Effects. A Critical Reevaluation of Clinical Data

Background: Recent advancements in heart failure (HF) therapy have significantly enhanced the management of patients across all phenotypes of left ventricular ejection fraction. However, these multidrug regimens frequently induce alterations in renal function by influencing intrarenal hemodynamics, thereby modifying glomerular ca-pillary pressures. This phenomenon could result in a mild to moderate decline in esti-mated glomerular filtration rate (eGFR), often classified as “worsening kidney function.” This nomenclature stems from consistent observations of eGFR reductions recorded during HF treatment in clinical trials. This review aims to clarify the implications of renal function changes linked to therapies that modify glomerular hemodynamics, and their relationship with patient outcomes. Methods: By a comprehensive re-examination of data from HF clinical trials conducted with various classes of medications, all affecting eGFR, we sought to provide evidence that the decline in eGFR is associated with the activation of specific mechanisms that collectively contribute to a reduction in glomerular filtration pressure, a prominent factor in maladaptive neurohormonal responses. Results: Since the investigation of angiotensin-converting enzyme inhibitors to the more recent non-steroidal mineralocorticoid receptor antagonist, the renal effects of these therapeutic regimens correlate with improvements in patient outcomes. The data consistently indicate that an early decline in eGFR, when coupled with an enhancement in HF outcomes, is associated with a more gradual decline in eGFR during long-term follow-up. Conclusion: Clinicians should recognize early declines in eGFR as indicators of favorable intra-glomerular hemodynamic adjustments that mitigate maladaptive neurohormonal re-sponses and contribute to improved long-term outcomes in patients with HF