Role of heme oxygenase in the regulation of the renal hemodynamics in a model of sex-dependent programmed hypertension by maternal diabetes.

Intrauterine programming of cardiovascular and renal function occurs in diabetes because of the adverse maternal environment. Heme oxygenase 1 (HO-1) and -2 (HO-2) exert vasodilatory and antioxidant actions, particularly in conditions of elevated HO-1 expression or deficient nitric oxide levels. We evaluated whether the activity of the heme-HO system is differentially regulated by oxidative stress in the female offspring of diabetic mothers, contributing to the improved cardiovascular function in comparison with males. Diabetes was induced in pregnant rats by a single dose of streptozotocin (STZ, 50 mg/kg ip) in late gestation. Three-month-old male offspring from diabetic mothers (MODs) exhibited higher blood pressure (BP), higher renal vascular resistance (RVR), worse endothelium-dependent response to acetylcholine (ACH), and an increased constrictor response to phenylephrine (PHE) compared with those in age-matched female offspring of diabetic mothers (FODs), which were abolished by chronic tempol (1 mM) treatment. In anesthetized animals, stannous mesoporphyrin (SnMP; 40 µmol/kg iv) administration, to inhibit HO activity, increased RVR in FODs and reduced glomerular filtration rate (GFR) in MODs, without altering these parameters in control animals. When compared with MODs, FODs showed lower nitrotirosyne levels and higher HO-1 protein expression in renal homogenates. Indeed, chronic treatment with tempol in MODs prevented elevations in nitrotyrosine levels and the acute renal hemodynamics response to SnMP. Then, maternal diabetes results in sex-specific hypertension and renal alterations associated with oxidative stress mainly in adult male offspring, which are reduced in the female offspring by elevation in HO-1 expression and lower oxidative stress levels.

Circulating levels of calprotectin, a signature of neutrophil activation in prediction of severe respiratory failure in COVID-19 patients: a multicenter, prospective study (CalCov study).

OBJECTIVE: Severe COVID-19 is characterized by a dysregulated immune response in which neutrophils play a critical role. Calprotectin reflects neutrophil activation and is involved in the self-amplifying thrombo-inflammatory storm in severe COVID-19. We aimed to evaluate the role of calprotectin in early prediction of severity in COVID-19 patients. METHODS: This was a multicenter prospective observational study enrolling consecutive adult COVID-19 patients. On arrival to emergency department, blood samples were collected for laboratory tests, including serum calprotectin. The primary outcome was severe respiratory failure requiring invasive mechanical ventilation and the secondary outcome was need for Intensive Care Unit (ICU) admission. RESULTS: Study population included 395 patients, 57 (14.4%) required invasive mechanical ventilation and 100 (25.3%) were admitted to ICU. Median serum calprotectin levels were significantly higher in intubated (3.73 mg/L vs. 2.63 mg/L; p < 0.001) and ICU patients (3.48 mg/L vs. 2.60 mg/L; p = 0.001). Calprotectin showed a significant accuracy to predict the need for invasive mechanical ventilation (ROC AUC 0.723) and ICU admission (ROC AUC 0.650). In multivariate analysis, serum calprotectin was an independent predictor of invasive mechanical ventilation (OR 1.161) and ICU admission (OR 1.068). CONCLUSION: Serum calprotectin can be used as an early predictor of severity in COVID-19 patients.

Role of Pancreatic Stone Protein as an Early Biomarker for Risk Stratification of Acute Pancreatitis.

BACKGROUND: Early risk stratification of acute pancreatitis is crucial to improve clinical outcomes. The objective of this study was to evaluate the ability of pancreatic stone protein (PSP) to predict acute pancreatitis severity and to compare it with the biomarkers and severity scores currently used for that purpose. PATIENTS AND METHODS: Prospective single-center observational study enrolling 268 adult patients with acute pancreatitis. Biomarkers including PSP were measured upon admission to the Emergency Department and severity scores as SOFA, PANC-3, and BISAP were computed. Patients were classified into mild-moderate (non-severe) and severe acute pancreatitis according to the Determinant-Based Classification Criteria. Area under the curve (AUC) and regression analysis were used to analyze the discrimination abilities and the association of biomarkers and scores with severity. RESULTS: Two hundred and thirty-five patients (87.7%) were classified as non-severe and 33 (12.3%) as severe acute pancreatitis. Median [IQR] PSP was increased in patients with severe acute pancreatitis (890 µg/L [559-1142] vs. 279 µg/L [141-496]; p < 0.001) and it was the best predictor (ROC AUC: 0.827). In multivariate analysis, PSP and urea were the only independent predictors for severe acute pancreatitis and a model combining them both ("biomarker model") showed an AUC of 0.841 for prediction of severe acute pancreatitis, higher than the other severity scores. CONCLUSIONS: PSP is a promising biomarker for predicting the severity of acute pancreatitis upon admission. A model combining PSP and urea might further constitute a potential tool for early risk stratification of this disease.

MR-proADM as marker of endotheliitis predicts COVID-19 severity.

BACKGROUND: Early identification of patients at high risk of progression to severe COVID-19 constituted an unsolved challenge. Although growing evidence demonstrates a direct association between endotheliitis and severe COVID-19, the role of endothelial damage biomarkers has been scarcely studied. We investigated the relationship between circulating mid-regional proadrenomedullin (MR-proADM) levels, a biomarker of endothelial dysfunction, and prognosis of SARS-CoV-2-infected patients. METHODS: Prospective observational study enrolling adult patients with confirmed COVID-19. On admission to emergency department, a blood sample was drawn for laboratory test analysis. Primary and secondary endpoints were 28-day all-cause mortality and severe COVID-19 progression. Area under the curve (AUC) and multivariate regression analysis were employed to assess the association of the biomarker with the established endpoints. RESULTS: A total of 99 patients were enrolled. During hospitalization, 25 (25.3%) cases progressed to severe disease and the 28-day mortality rate was of 14.1%. MR-proADM showed the highest AUC to predict 28-day mortality (0.905; [CI] 95%: 0.829-0.955; P < .001) and progression to severe disease (0.829; [CI] 95%: 0.740-0.897; P < .001), respectively. MR-proADM plasma levels above optimal cut-off (1.01 nmol/L) showed the strongest independent association with 28-day mortality risk (hazard ratio [HR]: 10.470, 95% CI: 2.066-53.049; P < .005) and with progression to severe disease (HR: 6.803, 95% CI: 1.458-31.750; P = .015). CONCLUSION: Mid-regional proadrenomedullin was the biomarker with highest performance for prognosis of death and progression to severe disease in COVID-19 patients and represents a promising predictor for both outcomes, which might constitute a potential tool in the assessment of prognosis in early stages of this disease.

Analyzing the capability of PSP, PCT and sCD25 to support the diagnosis of infection in cancer patients with febrile neutropenia.

Background Early diagnosis of infection is essential for the initial management of cancer patients with chemotherapy-associated febrile neutropenia (FN). In this study, we have evaluated two emerging infection biomarkers, pancreatic stone protein (PSP) and soluble receptor of interleukin 2, known as soluble cluster of differentiation 25 (sCD25), for the detection of an infectious cause in FN, in comparison with other commonly used infection biomarkers, such as procalcitonin (PCT). Methods A total of 105 cancer patients presenting to the emergency department were prospectively enrolled. We observed 114 episodes of chemotherapy-associated FN. At presentation, a blood sample was collected for the measurement of PCT, PSP and sCD25. In order to evaluate the discriminatory ability of these markers for the diagnosis of infection, the area under the curve (AUC) of the receiver operating characteristic curves was calculated. Results Infection was documented in 59 FN episodes. PCT, PSP and sCD25 levels were significantly higher in infected patients. PCT was the biomarker with the highest diagnostic accuracy for infection (AUC: 0.901), whereas PSP and sCD25 showed a similar performance, with AUCs of 0.751 and 0.730, respectively. In a multivariable analysis, PCT and sCD25 were shown to be independently associated with infection. Conclusions Two novel biomarkers, PSP and sCD25, correlated with infection in cancer patients with chemotherapy-associated FN, but neither PSP nor sCD25 improved the performance of PCT. Based on the results obtained, the introduction of these novel biomarkers as a tool for the diagnosis of infection in this patient group is not recommended.

In vitro stability of B-type natriuretic peptide (BNP) in plasma stored under different conditions when measured with the Lumipulse® assay.

Natriuretic peptides are a laboratory tool with significant implications for the diagnosis and prognosis of heart failure (HF). The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) recommended that assays must be examined for sample stability because there appears to be assay dependent. We aimed to evaluate the in vitro stability of B-type natriuretic peptide (BNP) under different handling conditions and using a BNP assay from Fujirebio Diagnostics (Tokyo, Japan). BNP concentrations were measured in plasma EDTA samples from 11 subjects to evaluate the in vitro stability at room temperature and at 4 °C and in 10 subjects to check the in vitro stability of samples stored at -20 °C during 1 and 3 months. Stability limit was defined according to Spanish Society of Laboratory Medicine (SEQC-ML) recommendations. At room temperature and 4 °C, BNP concentrations decreased progressively in samples collected in both groups, remaining stable within four hours from collection. BNP concentrations also were stable within four hours from collection in whole blood at room temperature. Finally, at -20 °C, BNP concentrations remained stable in both groups at 1 and 3 months, respectively. According to our results, BNP, stored at room temperature or at 4 °C, should be assayed in the first four hours after collection. Besides, BNP was shown to be stable in whole blood for at least four hours at room temperature. If the testing cannot be performed within the first four hours, the plasma should be frozen and kept at -20 °C for up to 3 months.

Pancreatic stone protein and soluble CD25 for infection and sepsis in an emergency department.

BACKGROUND: Infection is a common problem in emergency departments (EDs) and is associated with high mortality, morbidity and costs. Identifying infection in ED patients can be challenging. Biomarkers can facilitate its diagnosis, enabling an early management and improving outcomes. In the critical care setting, two emerging biomarkers, pancreatic stone protein (PSP) and soluble CD25 (sCD25), have demonstrated to be useful for diagnosis of sepsis. We aimed to assess the diagnostic value of these biomarkers, in comparison with procalcitonin (PCT), for infection and sepsis in an ED population with suspected infection. MATERIALS AND METHODS: Through a prospective, observational study, we investigated the utility of serum PCT, PSP and sCD25 levels, measured on admission, for diagnosis of infection and sepsis, defined according to the recently updated for sepsis (Sepsis-3), in patients presenting to the ED for suspected infection. Diagnostic accuracy was evaluated by using receiver operating characteristic curves (ROC) analysis. RESULTS: Of the 152 patients enrolled in this study, 129 had a final diagnosis of infection, including 82 with noncomplicated infection and 47 with sepsis. Median PCT, PSP and sCD25 levels were significantly higher in patients with infection and sepsis. The ROC curve analysis revealed a similar diagnostic accuracy for infection (ROC area under the curve (AUC) PCT: 0·904; sCD25: 0·869 and PSP: 0·839) and for sepsis (ROC AUC: PCT: 0·820; sCD25: 0·835 and PSP: 0·872). CONCLUSIONS: Pancreatic stone protein and sCD25 perform well as infection and sepsis biomarkers, with a similar performance than PCT, in ED patients with suspected infection. Further larger studies investigating use of PSP and sCD25 are needed.

Value of lipopolysaccharide binding protein as diagnostic marker of infection in adult cancer patients with febrile neutropenia: comparison with C-reactive protein, procalcitonin, and interleukin 6.

PURPOSE: Early detection of infection is essential for initial management of cancer patients with chemotherapy-associated febrile neutropenia in the emergency department. In this study, we evaluated lipopolysaccharide binding protein (LBP) as predictor for infection in febrile neutropenia and compared with other biomarkers previously studied: C-reactive protein (CRP), procalcitonin (PCT), and interleukin (IL)-6. METHODS: A total of 61 episodes of chemotherapy-associated febrile neutropenia in 58 adult cancer patients were included. Serum samples were collected on admission at emergency department and CRP, LBP, PCT, and IL-6 were measured. Patients were classified into fever of unknown origin and infection, including microbiologically and clinically documented infection, groups. Receiver operating characteristic (ROC) curve analysis was performed for each biomarker for the diagnosis of infection. RESULTS: Thirty-two of the 61 episodes were classified as infection. On admission, CRP, PCT, IL-6, and LBP were significantly increased in patients with infection compared to fever of unknown origin group. Area under the ROC curve (AUC ROC) of CRP, PCT, IL-6, and LBP for discriminating both groups was 0.77, 0.88, 0.82, and 0.82, respectively, without significant difference between them. The combination of IL-6 and PCT or LBP did not lead to a significant improvement of the diagnostic accuracy of PCT or LBP alone. CONCLUSIONS: On admission, LBP has a similar diagnostic accuracy than PCT or IL-6 for the diagnosis of infection and might be used as additional diagnostic tool in adult cancer patients with chemotherapy-associated febrile neutropenia.

Mortality prediction model from combined serial lactate, procalcitonin and calprotectin levels in critically ill patients with sepsis: A retrospective study according to Sepsis-3 definition.

OBJECTIVE: 1) To evaluate the ability of baseline and on 24 h serum calprotectin, in comparison to canonical biomarkers (lactate and procalcitonin), for prognosis of 28-day mortality in critically ill septic patients; and 2) To develop a predictive model combining the three biomarkers. DESIGN: A single-center, retrospective study. SETTING: Intensive Care Unit of a university hospital. PATIENTS OR PARTICIPANTS: One hundred and seventy three septic pacientes were included. INTERVENTIONS: Measurement of baseline lactate, procalcitonin and calprotectin level and procalcitonin and calprotectin levels on 24 h. MAIN VARIABLES OF INTEREST: Demographics and comorbidities, SOFA score on ICU admission, baseline lactate, procalcitonin and calprotectin on admission and on 24 h and 28-day mortality. RESULTS: 1) On ICU admission, lactate was the only biomarker achieving a significant accuracy (AUC: 0.698); 2) On 24 h, no differences were found on procalcitonin and calprotectin levels. Procalcitonin and calprotectin clearances were significantly lower in non-survivors and both achieved a moderate performance (AUCs: 0.668 and 0.664, respectively); 3) A biomarker based-model achieved a significant accuracy (AUC: 0.766), trending to increase (AUC: 0.829) to SOFA score alone; y 4) Baseline lactate levels and procalcitonin and calprotectin clearance were independent predictors for the outcome. CONCLUSIONS: 1) Baseline and on 24 h calprotectina and procalcitonin levels lacked ability in predicting 28-day mortality; 2) Accuracy of clearance of both biomarkers was moderate; and 3) Combination of SOFA score and the predictive biomarker based-model showed a high prognostic accuracy.

Observational study of lipid profile and LDL particle size in patients with metabolic syndrome.

BACKGROUND: The atherogenic lipoprotein phenotype is characterized by an increase in plasma triglycerides, a decrease in high-density lipoprotein cholesterol (HDLc), and the prevalence of small, dense-low density lipoprotein cholesterol (LDLc) particles. The aim of this study was to establish the importance of LDL particle size measurement by gender in a group of patients with Metabolic Syndrome (MS) attending at a Cardiovascular Risk Unit in Primary Care and their classification into phenotypes. SUBJECTS AND METHODS: One hundred eighty-five patients (93 men and 92 women) from several areas in the South of Spain, for a period of one year in a health centre were studied. Laboratory parameters included plasma lipids, lipoproteins, low-density lipoprotein size and several atherogenic rates were determinated. RESULTS: We found differences by gender between anthropometric parameters, blood pressure and glucose measures by MS status. Lipid profile was different in our two study groups, and gender differences in these parameters within each group were also remarkable, in HDLc and Apo A-I values. According to LDL particle size, we found males had smaller size than females, and patients with MS had also smaller than those without MS. We observed inverse relationship between LDL particle size and triglycerides in patients with and without MS, and the same relationship between all atherogenic rates in non-MS patients. When we considered our population in two classes of phenotypes, lipid profile was worse in phenotype B. CONCLUSION: In conclusion, we consider worthy the measurement of LDL particle size due to its relationship with lipid profile and cardiovascular risk.

An opportunity to emphasize the relevance of laboratory medicine.

Objectives: Clinical practice guidelines (CPGs) are recommendations based on a systematic review of scientific evidence that are intended to help healthcare professionals and patients make the best clinical decisions. CPGs must be evidence-based and are designed by multidisciplinary teams. The purpose of this study is to assess the topics related to the clinical laboratory addressed in CPGs and evaluate the involvement of laboratory professionals in the CPG development process. Methods: A total of 16 CPGs recommended by the Spanish Society of Laboratory Medicine and/or retrieved from PubMed-Medline were included. A review of the information provided in CPGs about 80 topics related to the clinical laboratory was performed. The authorship of laboratory professionals was assessed. Results: On average, the 16 CPGs addressed 49% (standard deviation [SD]: 11%) of the topics evaluated in relation to the clinical laboratory. By order of frequency, CPGs contained information about 69% of postanalytical variables (SD: 20%); 52% of preanalytical variables (SD: 11%); and 43% of the analytical variables studied (SD: 18%). Finally, half the CPGs included a laboratory professional among its authors. Conclusions: CPGs frequently failed to provide relevant laboratory-related information. Laboratory professionals were co-authors in only half the CPGs. There is scope for improvement, and laboratory professionals should be included in multidisciplinary teams involved in the development of CPGs.

[LDL concentration and particle size after treatment with rosiglitazone in patients with diabetes mellitus type 2]. / Concentración y tamaño de las partículas de LDL tras el tratamiento con rosiglitazona en pacientes con diabetes mellitus tipo 2.

BACKGROUND AND OBJECTIVE: The effects of rosiglitazone on the lipid profile are controversial, with related increases in the concentration of total and LDL cholesterol. Our objective is to evaluate the evolution of the concentration and size of LDL particles in a group of patients with type 2 diabetes mellitus taking rosiglitazone. PATIENTS AND METHODS: We studied 30 patients under treatment with oral antidiabetics to whom rosiglitazone was added to their initial therapy. The following tests were determined before and after 6 months of treatment: glucose, total cholesterol, HDL, LDL, triglycerides, C reactive protein, lipoprotein (a) and glycosylated haemoglobin. The average diameter of the particles LDL was also estimated, as well as the probability of cardiovascular events up to ten years, according to the Framingham and SCORE model. RESULTS: Statistically significant reductions of glucose, HbA(1C) and CRP levels, and an increase of total cholesterol, cholesterol LDL and triglycerides concentrations were observed, with statistical significance for total cholesterol. A significant increase in the estimation of cardiovascular risk up to ten years was found. No modifications either in the concentrations of HDL-c and Lp (a) or in the average size of LDL particles were detected. CONCLUSIONS: After treatment with rosiglitazone, there is an increase of total cholesterol concentrations without variation in the mean size of LDL particles. Nevertheless, the reduction of CRP, and thus of inflammation is clear, with prevention of the progression of atherosclerosis.

Prognostic value of procalcitonin and lipopolysaccharide binding protein in cancer patients with chemotherapy-associated febrile neutropenia presenting to an emergency department.

INTRODUCTION: Cancer patients with chemotherapy-induced febrile neutropenia are a heterogeneous group with a significant risk of serious medical complications. In these patients, the Multinational Association for Supportive Care in Cancer (MASCC) score is the most widely used tool for risk-stratification. The aim of this prospective study was to analyse the value of procalcitonin (PCT) and lipopolysaccharide binding protein (LBP) to predict serious complications and bacteraemia in cancer patients with febrile neutropenia, compared with MASCC score. MATERIALS AND METHODS: Data were collected from 111 episodes of febrile neutropenia admitted consecutively to the emergency department. In all of them, MASCC score was calculated and serum samples were collected for measurement of PCT and LBP by well-established methods. The main and secondary outcomes were the development of serious complications and bacteraemia, respectively. RESULTS: A serious complication occurred in 20 (18%) episodes and in 16 (14%) bacteraemia was detected. Areas under the receiver operating characteristic curve (ROC AUC) of MASCC score, PCT and LBP to select low-risk patients were 0.83 (95% confidence interval (CI): 0.74 - 0.89), 0.85 (95% CI: 0.77 - 0.91) and 0.70 (95% CI: 0.61 - 0.78), respectively. For bacteraemia, MASCC score, PCT and LBP showed ROC AUCs of 0.74 (95% CI: 0.64 - 0.82), 0.86 (95% CI: 0.78 - 0.92) and 0.76 (95% CI: 0.67 - 0.83), respectively. CONCLUSION: A single measurement of PCT performs similarly as MASCC score to predict serious medical complications in cancer patients with febrile neutropenia and can be a useful tool for risk stratification. Besides, low PCT concentrations can be used to rule-out the presence of bacteraemia.

Prognostic performance of pancreatic stone protein in critically ill patients with sepsis.

Aim: To assess the prognostic value for 28-day mortality of PSP in critically ill patients with sepsis. Material & methods: 122 consecutive patients with sepsis were enrolled in this study. Blood samples were collected on admission and day 2. Results: On admission, the combination of PSP and lactate achieved an area under the receiver operating characteristic (AUC-ROC) of 0.796, similar to sequential organ failure assessment score alone (AUC-ROC: 0.826). On day 2, PSP was the biomarker with the highest performance (AUC-ROC: 0.844), although lower (p = 0.041) than sequential organ failure assessment score (AUC-ROC: 0.923). Conclusion: The combination of PSP and lactate and PSP alone, on day 2, have a good performance for prognosis of 28-day mortality and could help to identify patients who may benefit most from tailored intensive care unit management.

Diagnostic accuracy of lipopolysaccharide-binding protein for sepsis in patients with suspected infection in the emergency department.

Background Biomarkers can facilitate the diagnosis of sepsis, enabling early management and improving outcomes. Lipopolysaccharide-binding protein (LBP) has been reported as a biomarker for the detection of infection, but its diagnostic value is controversial. In this study, we assessed the diagnostic accuracy of LBP for sepsis in the emergency department (ED) patients, comparing it with more established biomarkers of sepsis, including procalcitonin (PCT) and C-reactive protein (CRP). Methods LBP and other sepsis biomarkers, including PCT and CRP, were measured on admission in 102 adult patients presenting with suspected infection . Classification of patients was performed using the recently updated definition for sepsis (Sepsis-3). The diagnostic accuracy of LBP, CRP and PCT for sepsis was evaluated by using receiver operating characteristic curve (ROC) analysis. Results A total of 49 patients were classified as having sepsis. In these patients, median (interquartile range) LBP (41.8 [41.1] µg/dL vs. 26.2 [25] µg/dL), CRP (240 [205] mg/L vs. 160 [148] mg/dL) and PCT (5.19 [13.68] µg/L vs. 0.39 [1.09] µg/L) were significantly higher than in patients classified as not having sepsis ( P < 0.001 for all three biomarkers). ROC curve analysis and area under curve (AUC) revealed a value of 0.701 for LBP, similar to CRP (0.707) and lower than that for PCT (0.844) ( P = 0.012). Conclusion In adult ED patients with suspected infection, the diagnostic accuracy for sepsis of LBP is similar to that of CRP but lower than that of PCT.

Impact of kidney dysfunction on plasma and urinary N-terminal pro-B-type natriuretic peptide in patients with acute heart failure.

The precise mechanism explaining the increased N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations among patients with concomitant acute heart failure (AHF) and kidney dysfunction is not fully understood. The aim of this study was to assess the impact of kidney dysfunction on simultaneous measures of plasma and urinary NT-proBNP in an unselected cohort of patients with AHF. One hundred thirty-eight consecutive hospitalized patients (median age: 74 years; interquartile range: 67-80 years; 54% male) with a diagnosis of AHF were prospectively studied. Blood and urine samples were collected on hospital arrival to determine NT-proBNP concentrations. Both plasma and urinary NT-proBNP concentrations increased with declining estimated glomerular filtration rate (eGFR; P<.001 for both). However, after multivariate adjustment, eGFR was found to be an independent predictor of plasma (but not urinary) NT-proBNP concentration (eGFR: ß=-0.19; P=.016). Indeed, plasma NT-proBNP was the main independent determinant of its urinary concentration (ß=0.42; P<.001), and the ratio of urine/plasma NT-proBNP was independent of kidney function and similar across the range of eGFR examined (P=.368). In patients with AHF and concomitant kidney dysfunction, the increased circulating NT-proBNP may be mainly related to increased cardiac secretion and not decreased renal clearance.

Complementary prognostic value of cystatin C, N-terminal pro-B-type natriuretic Peptide and cardiac troponin T in patients with acute heart failure.

The aims of this study were to compare the prognostic value of cystatin C over creatinine and the Modification of Diet in Renal Disease (MDRD) equation and to evaluate whether it provides complementary information to cardiac biomarkers in the risk stratification of an unselected cohort of patients with acute heart failure. Consecutive hospitalized patients with established diagnoses of acute heart failure were prospectively studied. Blood samples were collected on hospital arrival to determine cystatin C, cardiac troponin T, and N-terminal-pro-brain natriuretic peptide. Clinical follow-up was obtained, and the occurrence of mortality and/or heart failure readmission was registered. One hundred thirty-eight patients (median age 74 years, interquartile range 67 to 80; 54% men) were studied. During a median follow-up period of 261 days (interquartile range 161 to 449), 60 patients (43.5%) presented with adverse events. After multivariate adjustment, cystatin C, N-terminal-pro-brain natriuretic peptide, cardiac troponin T, New York Heart Association functional class III or IV, and diabetes mellitus were identified as independent predictors of mortality and/or heart failure readmission. In contrast to creatinine and the MDRD equation, the highest cystatin C tertile (>1.50 mg/L) was a significant independent risk factor for adverse events (hazard ratio 3.08, 95% confidence interval 1.54 to 6.14, p = 0.004). A multimarker approach combining cardiac troponin T, N-terminal-pro-brain natriuretic peptide, and cystatin C improved risk stratification further, showing that patients with 2 (hazard ratio 2.37, 95% confidence interval 1.10 to 5.71) or 3 (hazard ratio 3.64, 95% confidence interval 1.55 to 8.56) elevated biomarkers had a higher risk for adverse events than patients with no elevated biomarkers (p for trend = 0.015). In conclusion, in this unselected cohort, cystatin C was a stronger predictor of adverse events than conventional measures of kidney function. In addition, cystatin C offered complementary prognostic information to cardiac biomarkers and could help clinicians perform more accurate risk stratification of patients with acute heart failure.