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Worsening renal function in acute heart failure in the context of diuretic response.

ABSTRACT:

Background

For patients with acute heart failure (AHF), substantial diuresis after administration of loop diuretics is generally associated with better clinical outcomes but may cause creatinine to rise, suggesting renal function decline. We investigated the interaction between diuretic response and worsening renal function (WRF) on clinical outcomes in patients with AHF.

Methods and results

In two AHF cohorts (PROTECT, n = 1698 and RELAX-AHF-2, n = 5586 in current analysis), the prognostic impact of WRF (creatinine ≥0.3 mg/dl increase baseline-day 4; sensitivity analyses incorporated baseline renal function) by diuretic response (kg weight loss/40 mg furosemide equivalent baseline-day 4) was investigated with regard to (cardiovascular) death or cardiovascular/renal hospitalization using subpopulation treatment effect pattern plots (STEPP) and survival analyses. WRF occurred in 286 (16.8%) and 1031 (18.5%) patients in PROTECT and RELAX-AHF-2, respectively. Patients with WRF had higher left ventricular ejection fraction and lower estimated glomerular filtration rate at baseline (p < 0.05), and received higher doses of loop diuretics and had a worse diuretic response (p < 0.001). In patients with a poor diuretic response (≤0.35 kg weight loss/40 mg furosemide equivalent as identified by STEPP), WRF was associated with higher risk of (cardiovascular) death or cardiovascular/renal hospitalization (p < 0.001 both cohorts), but this was not the case for patients with a good diuretic response (p = 0.900 both cohorts).

Conclusion

In two large cohorts of patients with AHF, WRF in the first 4 days was not associated with worse outcomes when patients had a good diuretic response. The occurrence of WRF in patients with AHF should therefore be considered in the context of diuretic response.

SUBMITTER: Emmens JE

PROVIDER: S-EPMC9300008 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Despite the fact that loop diuretics are a landmark in acute heart failure (AHF) treatment, few trials exist that evaluate whether the duration and timing of their administration and drug amount affect outcome. In this study, we sought to evaluate different loop diuretic infusion doses in relation to outcome and to diuretic response (DR), which was serially measured during hospitalization. METHODS:This is a post-hoc analysis of a DIUR-HF trial. We divided our sample on the basis of intravenous diuretic dose during hospitalization. Patients taking less than 125 mg of intravenous furosemide (median value) were included in the low dose group (LD), patients with a diuretic amount above this threshold were inserted in the high dose group (HD). The DR formula was defined as weight loss/40 mg daily of furosemide and it was measured during the first 24 h, 72 h, and over the whole infusion period. Outcome was considered as death due to cardiovascular causes or heart failure hospitalization. RESULTS:One hundred and twenty-one AHF patients with reduced ejection fractions (EF) were evaluated. The cardiovascular (CV) death/heart failure (HF) re-hospitalization rate was significantly higher in the HD group compared to the LD group (75% vs. 22%; p < 0.001). Both low DR, measured during the entire infusion period (HR 3.25 (CI: 1.92-5.50); p < 0.001) and the intravenous diuretic HD (HR 5.43 [CI: 2.82-10.45]; p < 0.001) were related to outcome occurrence. Multivariable analysis showed that DR (HR 3.01 (1.36-6.65); p = 0.006), intravenous diuretic HD (HR 2.83 (1.24-6.42); p=0.01) and worsening renal function (WRF) (HR 2.21 (1.14-4.28); p = 0.01) were related to poor prognosis. CONCLUSIONS:HD intravenous loop diuretic administration is associated with poor prognosis and less DR. Low DR measured during the whole intravenous administration better predicts outcome compared to DR measured in the early phases. ClinicalTrials.gov Acronym and Identifier Number: DIUR-HF; NCT01441245; registered on 23 September 2011.

Project description:AimsThe importance of true worsening renal failure (WRF), which is associated with a poor prognosis, had been suggested in patients with acute heart failure (AHF). The aim of the present study was to establish the biomarker strategy for the prediction of true WRF in AHF.Methods and resultsTwo hundred eighty-one patients with AHF were analysed. Their biomarkers were measured within 30 min of admission. Patients were assigned to the non-WRF (n = 168), pseudo-WRF (n = 56), or true-WRF (n = 57) groups using the criteria of both acute kidney injury on admission and increasing serum creatinine value during the first 7 days. A Kaplan-Meier curve showed that the survival and heart failure event rate of the true-WRF group within 1000 days was significantly lower than that of the non-WRF and pseudo-WRF groups (P ≤ 0.001). The multivariate Cox regression model also indicated that true WRF was an independent predictor of 1000 day mortality and heart failure events [hazard ratio: 4.315, 95% confidence interval (CI): 2.466-7.550, P ≤ 0.001, and hazard ratio: 2.834, 95% CI: 1.893-4.243, P ≤ 0.001, respectively]. The serum heart-type fatty acid-binding protein (s-HFABP) levels were significantly higher in the true-WRF group than in the non-WRF and pseudo-WRF groups (P ≤ 0.001). The multivariate logistic regression model indicated that the predictive biomarker for the true-WRF group was the s-HFABP level (odds ratio: 5.472, 95% CI: 2.729-10.972, P ≤ 0.001). The sensitivity and specificity for indicating the presence of true WRF were 73.7% and 76.8% (area under the curve = 0.831) for s-HFABP in whole patients, respectively, and 94.7% and 72.7% (area under the curve = 0.904) in non-chronic kidney disease (CKD) patients, respectively.ConclusionsCardiac biomarkers, especially the s-HFABP, might predict the development of true WRF in AHF patients. Furthermore, the predictive value was higher in AHF patients without CKD than in those with CKD.