Elevated urinary kidney injury molecule 1 at discharge strongly predicts early mortality following an episode of acute decompensated heart failure.

INTRODUCTION: Hospitalization for acute decompensation of heart failure (ADHF) is a frequent event associated with long­term adverse effects. Prognosis is even worse if acute kidney injury (AKI) occurs during hospitalization. OBJECTIVES: The study aimed to determine whether kidney damage biomarkers neutrophil gelatinase­associatedlipocalin (NGAL), kidney injury molecule 1 (KIM­1), and interleukin18 (IL­18) might predict AKI and have prognostic value in ADHF. PATIENTS AND METHODS: Serum NGAL on admission and urine NGAL, KIM­1, and IL­18 on discharge were determined in 187 ADHF patients enrolled in a prospective, observational, unblinded study. AKI was diagnosed using the Kidney Disease: Improving Global Outcomes criteria. Patients were followedfor 12 months to record all­cause mortality. RESULTS: A total of 22% patients died during the follow­up, with 52.5% dying within 4 months after discharge. Serum NGAL (P <0.001), urine NGAL (P = 0.047), and urinary KIM­1 (P = 0.014) levels were significantly higher in the deceased patients at discharge. After adjustment for estimated glomerular filtration rate (eGFR), only urinary KIM­1 independently predicted mortality at month 4 (hazard ratio [HR], 3.166; 95% CI, 1.203-8.334; P = 0.020) and month 12 (HR, 1.969; 95% CI, 1.123-3.454; P = 0.018) in Cox regression models. In receiver operating characteristic (ROC) analysis urinary KIM­1 (area under the ROC curve [AUC] = 0.830) outperformed other markers of renal function. The Kaplan-Meier survival analysis showed KIM­1 predictive value as additive to that of AKI incidence and admission eGFR. Admission serum NGAL was higher in AKI patients (P ≤0.001) with a modest diagnostic performance (AUC = 0.667), below that of urea (AUC = 0.732), creatinine (AUC = 0.696), or cystatin C (AUC = 0.676). CONCLUSIONS: Discharge urinary KIM­1 was a strong and independent predictor of mortality, particularly during the most vulnerable period shortly after hospitalization. Admission serum NGAL was inferior to conventional renal function parameters in predicting AKI during ADHF.

Prevalence, predictors and clinical outcome of residual congestion in acute decompensated heart failure.

BACKGROUND: Congestion is the main reason for hospital admission for acute decompensated heart failure (ADHF). A better understanding of the clinical course of congestion and factors associated with decongestion are therefore important. We studied the clinical course, predictors and prognostic value of congestion in a cohort of patients admitted for ADHF by including different indirect markers of congestion (residual clinical congestion, brain natriuretic peptides (BNP) trajectories, hemoconcentration or diuretic response). METHODS AND RESULTS: We studied the prognostic value of residual clinical congestion using an established composite congestion score (CCS) in 1572 ADHF patients. At baseline, 1528 (97.2%) patients were significantly congested (CCS ≥ 3), after 7 days of hospitalization or discharge (whichever came first), 451 (28.7%) patients were still significantly congested (CCS ≥ 3), 751 (47.8%) patients were mildly congested (CCS = 1 or 2) and 370 (23.5%) patients had no signs of residual congestion (CCS = 0). The presence of significant residual congestion at day 7 or discharge was independently associated with increased risk of re-admissions for heart failure by day 60 (HR [95%CI] = 1.88 [1.39-2.55]) and all-cause mortality by day 180 (HR [95%CI] = 1.54 [1.16-2.04]). Diuretic response provided added prognostic value on top of residual congestion and baseline predictors for both outcomes, yet gain in prognostic performance was modest. CONCLUSION: Most patients with acute decompensated heart failure still have residual congestion 7 days after hospitalization. This factor was associated with higher rates of re-hospitalization and death. Decongestion surrogates, such as diuretic response, added to residual congestion, are still significant predictors of outcomes, but they do not provide meaningful additive prognostic information.

Cystatin C-based CKD-EPI equations and N-terminal pro-B-type natriuretic peptide for predicting outcomes in acutely decompensated heart failure.

BACKGROUND: In patients with acute decompensated heart failure (ADHF), both natriuretic peptides and renal impairment predict adverse outcomes. Our aim was to evaluate the complementary prognosis role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and the newly developed Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations based on cystatin C (CysC) for glomerular filtration rate (GFR) estimation in ADHF patients. HYPOTHESIS: Renal impairment assessed by CysC-based CKD-EPI equations and natriuretic peptides have complementary prognostic value in ADHF patients. METHODS: The study included 613 consecutive patients presenting with ADHF. At admission, plasma levels of NT-proBNP and CysC were determined. The GFR was estimated using CysC-based CKD-EPI equations. The primary endpoint was death from any cause and heart failure readmission. RESULTS: During the median follow-up of 365 days (interquartile range, 227-441 days), 323 patients (0.65 %patient-year) died or were readmitted for heart failure. After multivariate adjustment, estimated GFR <60 mL/min/1.73 m(2) and NT-proBNP >3251 pg/mL were independent predictors of adverse outcomes (P < 0.01). The combination of GFR <60 mL/min/1.73 m(2) and NT-proBNP >3251 pg/mL was associated with the highest risk of adverse outcomes. Furthermore, reclassification analyses demonstrated that use of both NT-proBNP and CysC-based CKD-EPI equations resulted in improving the accuracy for adverse outcomes prediction. CONCLUSIONS: In patients with ADHF, the combination of NT-proBNP with estimated GFR using CysC-based CKD-EPI equations better predicts outcomes than either parameter alone and adds valuable complementary prognosis information to other established risk factors.

Heart failure mortality according to acute variations in N-terminal pro B-type natriuretic peptide and cystatin C levels.

AIM: Changes in N-terminal pro B-type natriuretic peptide (NT-proBNP) levels and cystatin C (CysC) are predictors of adverse outcomes in acute heart failure. This study assess whether NT-proBNP variations might provide independent information in addition to that obtained from CysC levels. METHODS: NT-proBNP levels were assessed in patients admitted due to acute heart failure using an observational study. Patients were classified as follows: group 1, those with a decrease in NT-proBNP levels of at least 30% from admission to 4 weeks after discharge; group 2, those with no significant changes in levels; and group 3, those who showed an increase in NT-proBNP of 30%. A multivariable Cox regression model and c-statistics were used. The primary end-point was all-cause mortality at 1-year follow-up. RESULTS: A total of 195 patients completed the follow-up. The mortality rate reached 20.5% (40 patients); 14 out of the 32 in group 3. The cumulative incidence of death, according to the change in NT-proBNP and Kaplan-Meier analysis, showed a significant increase in group 3 (log-rank P = 0.004). In the multivariable analysis, NT-proBNP variation for group 3 (hazard ratio 4.27; P <0.001) and for group 2 (hazard ratio 2.19; P = 0.043) in comparison with group 1 were independently associated with all-cause mortality, as well as anemia, hyponatremia, and admission CysC levels. Patients in group 3, and those with levels of serum CysC above the median, were also associated with slight increase in mortality. CONCLUSION: An increase of at least 30% in NT-proBNP levels after hospitalization is related to all-cause mortality in patients with acute heart failure and provides supplementary prognostic information in patients with high levels of CysC. A decrease in NT-proBNP of at least 30% is a desirable target to achieve.

Comparison of risk prediction with the CKD-EPI and MDRD equations in acute decompensated heart failure.

BACKGROUND: Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations estimate glomerular filtration rate (eGFR) more accurately than the Modification of Diet in Renal Disease (MDRD) equation. The aim of this study was to evaluate whether CKD-EPI equations based on serum creatinine and/or cystatin C (CysC) predict risk for adverse outcomes more accurately than the MDRD equation in a hospitalized cohort of patients with acute decompensated heart failure (ADHF). METHODS AND RESULTS: A total of 526 subjects with ADHF were studied. Blood was collected within 48 hours from admission. eGFR was calculated with the use of MDRD and CKD-EPI equations. The occurrences of mortality and heart failure (HF) hospitalization were recorded. Over the study period (median 365 days [interquartile range 238-370]), 305 patients (58%) died or were rehospitalized for HF. Areas under the receiver operator characteristic curves for CKD-EPI CysC and CKD-EPI creatinine-CysC equations were significantly higher than that for the MDRD equation, especially in patients with >60 mL min(-1) 1.73 m(-2). After multivariate adjustment, all eGFR equations were independent predictors of adverse outcomes (P < .001). However, only CKD-EPI CysC and CKD-EPI creatinine-CysC equations were associated with significant improvement in reclassification analyses (net reclassification improvements 10.8% and 12.5%, respectively). CONCLUSIONS: In patients with ADHF, CysC-based CKD-EPI equations were superior to the MDRD equation for predicting mortality and/or HF hospitalization especially in patients with >60 mL min(-1) 1.73 m(-2), and both CKD-EPI equations improved clinical risk stratification.

Differential prognostic utility of NTproBNP and Cystatin C in patients with acute exacerbation of chronic pulmonary disease.

OBJECTIVES: To determine whether serum Cystatin C (CysC) and NTproBNP have prognostic value among patients with long-standing chronic lung disease. DESIGN: Prospective, observational, non-interventional study. SETTING: CysC and NTproBNP are prognostic markers in several cardiac conditions. In addition, CysC acts as an antiprotease following Cathepsin activation, which has been involved in the pathogenesis of chronic obstructive pulmonary disease. PARTICIPANTS: Patients with a basal functional status of II-IV (NYHA), admitted for an acute exacerbation of chronic pulmonary diseases and no previous history of symptoms related to pulmonary hypertension or heart failure. MAIN OUTCOME MEASURES: NTproBNP and CysC were determined at admission in 107 patients with acute exacerbation of chronic lung disease. During 12-month follow-up, mortality, new hospital admissions and prescription of diuretics were recorded. RESULTS: During follow-up there were eight patient deaths (7.5%). Mean NTproBNP among the deceased was 1510.20 pg/mL (95% CI 498.44-4628.55) vs 502.70 pg/mL (95% CI 395.44-645.48) among survivors (p = 0.01). Twenty-seven patients (25%) were prescribed loop diuretics. Mean concentration of CysC was 1.45 mg/dL (95% CI 1.21-1.69 mg/dL) vs 1.17 mg/dL (95% IC 1.09-1.25 mg/dL) in those not prescribed (p = 0.004). NTproBNP concentration was 837.14 pg/mL (95% CI 555.57-1274.10 pg/mL) in patients prescribed diuretics vs 473.42 pg/mL (95% CI 357.80-632.70 pg/mL) in those not prescribed (p = 0.03). Kaplan-Meier analysis revealed a significant difference between death and diuretic prescription during follow-up when cut-off value for NTproBNP was 550 pg/mL (p = 0.03 and p = 0.02, respectively). For 1.16mg/dL of CsysC, a significant difference was only observed in diuretic prescription (p = 0.007). CONCLUSIONS: In patients with chronic respiratory diseases NTproBNP has predictive value in terms of mortality whereas CysC does not. However, it is still possible that both can contribute to the early identification of patients at risk of developing clinical ventricular dysfunction.