Worsening Renal Function and Mortality in Heart Failure
Causality or Confounding?
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- cardio-renal syndrome
- glomerular filtration rate
- heart failure
- renin-angiotensin system
- worsening renal function
Worsening renal function (WRF) is common during the treatment of heart failure (HF) and has been associated with decreased survival, hospitalization, and disease progression.1 There are several hypothetical mechanisms, including inflammation, oxidant stress, or induction of apoptosis by uremic toxins, by which a reduction in renal function could directly lead to mortality.2,3 However, patients who experience WRF also often exhibit multiple markers of increased HF disease severity and are less likely to respond to diuretics.4,5 As a result, it is difficult to determine whether the frequently observed association between WRF and adverse outcomes results directly from the reduction in glomerular filtration rate (GFR) or is merely serving as a marker of greater HF disease severity.
See Article by Beldhuis et al
Over the past several years, it been described that not all forms of WRF are prognostically equivalent and WRF that occurs in the setting of otherwise beneficial HF therapies, like renin–angiotensin–aldosterone system (RAAS) antagonists or aggressive diuresis, seems to have a negligible impact on outcomes.6–10 RAAS antagonists, a cornerstone of guideline-based medical therapy for HF with reduced ejection fraction (HFrEF), can lead to perturbations in glomerular hemodynamics, secondary to a more pronounced vasodilation of the efferent arteriole, yielding a decrease in filtration fraction and thus at times GFR.11 As a result, it is not surprising that WRF is commonly observed during treatment with these medications.7,12 Despite the increased frequency of WRF, we and others have found that WRF in the setting of HFrEF treated with RAAS antagonists is relatively benign compared with WRF unprovoked by RAAS antagonism.7,9,12 So although the evidence for prognostic subtypes of WRF is well established, questions remain as to what causes the difference in prognosis. Is …