Improving renal function during diuresis: useful information or just noise?

This article refers to ‘Decongestion discriminates risk for one-year mortality in patients with improving renal function acute heart failure’ by N. Wettersten et al., published this issue on pages 1122–1130. Researchers and clinicians continue attempts at decoding the meaning of changes creatinine during treatment decompensated failure (ADHF). Over past two decades, data have accumulated indicating that, a population level, worsening (WRF) is associated reduced survival.1, 2 Based these consistent observations, many us assumed causal relationship between reduction kidney worse outcomes. However, recent challenged assumptions demonstrating that WRF setting beneficial therapies, such as effective decongestion or neurohormonal antagonist titration, neutral even improved outcomes.3-5 Two potential explanations paradox are (1) therapeutic benefit intervention overwhelms direct negative effect WRF, (2) ADHF primarily serve marker disease severity haemodynamic perturbations, without WRF. The more observation (IRF) worsened outcomes strong indicator #2 primary factor.6 While theories animal experiments support hypotheses why could effect, it hard postulate how improvement directly worsen survival. We also know we can improve expense overall (HF) status. In clever study illustrating point, had all HF medications suspended 48 h. Here saw significantly came doubling natriuretic peptides New York Heart Association class.7 emerging narrative from presence directionality small moderate sized provides minimal actionable information. Rather, clinical context underlying paramount determining outcome change. Journal, al. 8 adds discussion. Evaluating 760 enrolled into AKINESIS trial, authors sought understand incomplete IRF. IRF was defined ≥20% increase estimated glomerular filtration rate, which occurred 22% population. Adequate ≥40% B-type peptide (BNP), approximately 44% Similar prior studies, appeared largely product pre-admission higher rate post-discharge mortality. appear share similar trajectories different categorization based clinician's perspective baseline (Figure 1). When outpatient several months unknown, selection serum admission ‘baseline creatinine’ alters diagnosis threefold compared other definitions function.9 new important entirely dependent level achieved hospital. Notably, inadequate dramatically increased death their well decongested non-IRF counterparts. adequate decongestion, there no statistically significant These observations reenforce concept critical treatment, should not modify therapy creatinine. To end, bump isolation dissuade continued diuresis congested patient. Additionally, current findings somewhat counterintuitive notion an may imply substantial residual congestion need additional diuresis. Of 166 study, 109 (66%) did achieve least 40% BNP. surprising since will lead clearance peptides, thus further lowering BNP levels independent any change congestion. would speculation remaining most help explain majority explainable Although limited numbers, analysis transient vs. persistent allows some intersection function. met criteria time hospitalization, 60 longer discharge. previous our group IRF, length stay.6 Thus, one assume either (i.e. titration antagonists) (e.g. refill intravascular compartment extravascular space) leading re-worsening substantially greater (6.9 4.8 L, P = 0.004) 30% better long-term survival patients.6 found opposite; having than By definition IRF–mortality associations confounding; marker, cause, outcomes, be contradictory. upon close inspection subgroups congestion, potentially signal emerges. Specifically, (n 45), 38%, cohort. speculate in-hospital deterioration 15), only 7% very 274, 9%). has repeatedly been so surprising. number, once again line creatinine, whether post IRF-WRF, interpreted within Despite fact relatively message now emerged large observational literature ADHF, if anything rather fewer questions respond clinically. For example, clear occurs aggressive itself free prognostic significance. suggest when decrease absence But what do information? Does mean ignore diuresis? Is threshold point becomes too severe, starts significance? enter completely zone. reality conclusions drawn generated era physicians were working preserve As result nephroprotective approach treating sparse happens dramatic rules abandon concern about modest same hold up? Just like shooting ended up somewhere around one-third admissions increase, shoot assuredly end accidentally causing 2). How ultimately impact unknowable. Short waiting another 20 years see ‘permissive hypercreatininaemia’ produce, randomized trials evaluating strategies required gain definitive understanding ADHF. Conflict interest: J.M.T. reports grants personal fees 3ive Labs, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Astra Zeneca, Novartis, Cardionomic, MagentaMed, Reprieve Inc., FIRE1, W.L. Gore, Sanofi, Sequana Medical, Otsuka, Abbott, Merck, Windtree Therapeutics, Lexicon pharmaceuticals, Precardia. addition, patent Treatment diuretic resistance issued Yale Corvidia Therapeutics Inc, Methods measuring renalase Yale, resistance. All nothing disclose.