Proenkephalin and Renal Dysfunction in Acute Heart Failure

Study Questions:

What is the prognostic value of proenkephalin in acute heart failure (HF) in predicting renal dysfunction?


The authors in this multicenter study measured proenkephalin in 1,908 acute HF patients (1,186 males; mean age, 75.66 ± 11.74 years). The primary endpoint was 1-year all-cause mortality; secondary endpoints were in-hospital mortality, all-cause mortality or HF rehospitalization within 1 year, and in-hospital worsening renal function, defined as a rise in serum creatinine ≥0.3 mg/dl or 50% above the admission value within 5 days of presentation.


During 1-year follow-up, 518 patients died and proenkephalin levels independently predicted worsening renal function (odds ratio, 1.58; 95% confidence interval [CI], 1.24-2.00; p < 0.0005) with a model receiver operating characteristic (ROC) area of 0.69 (95% CI, 0.65-0.73) compared to 0.67 (95% CI, 0.63-0.71) for a model without proenkephalin (p value for difference in ROC areas = 0.054). Proenkephalin was associated with the degree of worsening renal function. Using multivariable Cox regression models, the study investigators found that proenkephalin level was an independent predictor of 1-year mortality (p < 0.0005) and 1-year death and/or HF (hazard ratio, 1.27; 95% CI, 1.10-1.45; p = 0.001). Moreover, proenkephalin levels independently predicted outcomes at 3 or 6 months and were independent predictors of in-hospital mortality, predominantly down-classifying risk in survivors when added to clinical scores; levels <133.3 pmol/L and >211.3 pmol/L detected low- and high-risk patients, respectively.


The authors found that proenkephalin levels reflect cardiorenal status in acute HF and are prognostic for worsening renal function and in-hospital mortality as well as mortality during follow-up.


This is an important study because it suggests that proenkephalin is an important biomarker in predicting worsening renal function in patients with acute decompensated HF. Further studies are needed to validate these findings, discern whether these findings can be reproduced in all ethnic groups, and most importantly, result in therapeutic changes that actually improve patient outcomes.

Clinical Topics: Anticoagulation Management, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Acute Kidney Injury, Biological Markers, Creatinine, Enkephalins, Geriatrics, Heart Failure, Hospital Mortality, Prognosis, Protein Precursors, ROC Curve, Renal Insufficiency, Risk, Survival

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