Cardiovascular-Kidney-Metabolic Syndrome: Association with Adverse Events After Major Noncardiac Surgery.

BACKGROUND: The American Heart Association (AHA) recently defined the cardiovascular-kidney-metabolic syndrome (CKM) as a new entity to address the complex interactions between heart, kidneys, and metabolism. The aim of this study was to assess the outcome impact of CKM syndrome in patients undergoing noncardiac surgery. METHODS: This is a secondary analysis of a prospective international cohort study including patients aged ≥45 years with increased cardiovascular risk undergoing noncardiac surgery. Main exposure was CKM syndrome according to the AHA definition. The primary end point was a composite of major adverse cardiovascular events (MACE) 30 days after surgery. Secondary end points included all-cause mortality and non-MACE complications (Clavien-Dindo class ≥3). RESULTS: This analysis included 14,634 patients (60.8% male, mean age = 72±8 years). MACE occurred in 308 patients (2.1%), and 335 patients (2.3%) died. MACE incidence by CKM stage was as follows: CKM 0: 5/367 = 1.4% (95% confidence interval [CI], 0.4%-3.2%); CKM 1: 3/367 = 0.8% (95% CI, 0.2%-2.4%); CKM 2: 102/7440 = 1.4% (95% CI, 1.1%-1.7%); CKM 3: 27/953 = 2.8% (95% CI, 1.9%-4.1%); CKM 4a: 164/5357 = 3.1% (95% CI, 2.6%-3.6%); CKM 4b: 7/150 = 4.7% (95% CI, 1.9%-9.4%). In multivariate logistic regression, CKM stage ≥3 was independently associated with MACE, mortality, and non-MACE complications, respectively (MACE: OR 2.26 [95% CI, 1.78-2.87]; mortality: OR 1.42 [95% CI: 1.13 -1.78]; non-MACE complications: OR 1.11 [95% CI: 1.03-1.20]). CONCLUSION: The newly defined CKM syndrome is associated with increased morbidity and mortality after non-cardiac surgery. Thus, cardiovascular, renal, and metabolic disorders should be regarded in mutual context in this setting.

Intra-abdominal pressure and its relationship with markers of congestion in patients admitted for acute decompensated heart failure.

Systemic congestion is one of the mechanisms involved in acute decompensated heart failure (ADHF). Increased intra-abdominal pressure (IAP), elicited by abdominal congestion, has been related to acute kidney injury and prognosis. Nonetheless, the link between diuretic response, surrogate markers of congestion and renal function remains poorly understood. We measured IAP in 43 patients from a non-interventional, exploratory, prospective, single center study carried out in patients admitted for ADHF. IAP was measured with a calibrated electronic manometer through a catheter inserted in the bladder. Normal IAP was defined as < 12 mmHg. At baseline, median IAP was 15 mmHg, with a reduction over the next 72 h to a median of 12 mmHg. A higher IAP at admission was associated with higher baseline blood urea (83 mg/dL [62-138] vs. 50 mg/dL [35-65]; p = 0.007) and creatinine (1.30 mg/dL vs. 0.95 mg/dL; p = 0.027), and with poorer diuretic response 72 h after admission, either measured by diuresis (14.4 mL/mg vs. 21.6 mL/mg; [p = 0.005]) or natriuresis (1.2 mEqNa/mg vs. 2.0 mEqNa/mg; [p = 0.008]). A higher incidence for 1-year all-cause mortality (45.0% vs. 16.7%; log-rank test = 0.041) was observed among those patients with IAP > 12 mmHg at 72 h. In patients with ADHF, higher IAP at admission is associated with poorer baseline renal function and impaired diuretic response. The persistence of IAP at 72 h above 12 mmHg associates to longer length of hospital stay and higher 1-year all-cause mortality.

Association of Optimal Blood Pressure With Critical Cardiorenal Events and Mortality in High-Risk and Low-Risk Patients Treated With Antihypertension Medications.

Importance: There are few studies comparing the optimal level of treated blood pressure (BP) between high- and low-risk patients. Objective: To examine whether optimally treated BP is different according to risk status. Design, Setting, and Participants: Population-based cohort study using data from the National Health Information Database in Korea from 2002 to 2015 and 2006 to 2017. A total of 1 402 975 adults aged 40 to 79 years who had no known cardiorenal disease were included. Exposures: Systolic BP treated with antihypertensive medication. Main Outcomes and Measures: The yearly rates of critical cardiorenal events and all-cause death were estimated according to the levels of treated systolic BP and the presence of 5 risk factors (hypertension, diabetes, hyperlipidemia, proteinuria, and smoking). Results: During the study periods, 225 103 of 487 412 participants (54.0% male; median [interquartile range] age, 50 [44-59] years) in the primary cohort and 360 503 of 915 563 participants (50.1% male; median [interquartile range] age, 52 [46-60] years) in the secondary cohort received antihypertensive treatment. In total, 28 411 of 51 292 cardiorenal incidents and 33 102 of 72 500 deaths were noted in ever-treated participants. The absolute increase in cardiorenal and mortality risk associated with inadequately treated BP was greater in participants with multiple risk factors than in those with 1 or 0 risk factors. The hazard ratios for critical cardiorenal events increased as the treated systolic BP increased to more than 130 to 140 mm Hg. The hazard ratio for all-cause mortality for patients with 3 or more risk factors and treated systolic BP within the range of 110 to 119 mm Hg was 1.21 (95% CI, 1.07-1.37); 130 to 139 mm Hg, 1.04 (95% CI, 0.98-1.11); 140 to 149 mm Hg, 1.12 (95% CI, 1.05-1.20); 150 to 159 mm Hg, 1.21 (95% CI, 1.11-1.32); and 160 mm Hg or greater, 1.46 (95% CI, 1.32-1.62) compared with high-risk patients with BP of 120 to 129 mm Hg. For participants with 1 or 0 risk factors and treated systolic BP within the range of 110 to 119 mm Hg, the hazard ratio was 1.14 (95% CI, 1.07-1.22); 130 to 139 mm Hg, 0.97 (95% CI, 0.93-1.02); 140 to 149 mm Hg, 1.00 (95% CI, 0.91-1.09); 150 to 159 mm Hg, 1.06 (95% CI, 0.99-1.14); and 160 mm Hg or greater, 1.26 (95% CI, 1.15-1.37). However, when categorized using cardiovascular risk calculators, there was no consistent trend in mortality thresholds of BP across the risk score categories. Conclusions and Relevance: These results suggest that intensive BP control is appropriate for reducing all-cause mortality in addition to cardiorenal risk in higher- rather than lower-risk patients. However, caution may be required when determining BP targets using current risk calculators.

Use of Levosimendan in Intensive Care Unit Settings: An Opinion Paper.

Levosimendan is an inodilator that promotes cardiac contractility primarily through calcium sensitization of cardiac troponin C and vasodilatation via opening of adenosine triphosphate-sensitive potassium (KATP) channels in vascular smooth muscle cells; the drug also exerts organ-protective effects through a similar effect on mitochondrial KATP channels. This pharmacological profile identifies levosimendan as a drug that may have applications in a wide range of critical illness situations encountered in intensive care unit medicine: hemodynamic support in cardiogenic or septic shock; weaning from mechanical ventilation or from extracorporeal membrane oxygenation; and in the context of cardiorenal syndrome. This review, authored by experts from 9 European countries (Austria, Belgium, Czech republic, Finland, France, Germany, Italy, Sweden, and Switzerland), examines the clinical and experimental data for levosimendan in these situations and concludes that, in most instances, the evidence is encouraging, which is not the case with other cardioactive and vasoactive drugs routinely used in the intensive care unit. The size of the available studies is, however, limited and the data are in need of verification in larger controlled trials. Some proposals are offered for the aims and designs of these additional studies.

Toward Precision Medicine in the Cardiorenal Syndrome.

Although the field of oncology has made significant steps toward individualized precision medicine, cardiology and nephrology still often use a "one size fits all" approach. This applies to the intersection of the heart-kidney interaction and the cardiorenal syndrome as well. Recent studies have shown that the prognostic implications of worsening renal function (WRF) in acute heart failure are variable; thus, there is a need to differentiate the implications of WRF to better guide precise care. This may best be performed with biomarkers that can give the clinician a real-time evaluation of the physiologic state at the time of developing WRF. This review will summarize current cardiac and renal biomarkers and their status in the evaluation of cardiorenal syndrome. Although we have made progress in our understanding of this syndrome, further investigation is needed to bring precision medicine into routine clinical practice for the care of patients with cardiorenal syndrome.

Malnutrition is prevalent in patients with cardiorenal syndrome and negatively influences clinical outcome.

Cardiorenal syndrome (CRS) describes the concurrent failure of cardiac and renal function, each influencing the other. Malnutrition and cachexia frequently develop in patients with heart failure or kidney failure. However, no information is currently available on the prevalence of malnutrition in CRS patients. We studied CRS patients admitted to an internal medicine ward during a 5-month period and evaluated their clinical characteristics and nutritional status. Malnutrition risk was assessed by using the validated screening tool NRS-2002 whilst body composition was assessed by bioimpedance analysis and muscle function was measured by handgrip (HG) strength. Cardiac mass was also recorded. Length of stay, hospital readmission and 6-month mortality were registered. During the study period, 22 CRS patients were studied. Twenty patients were diagnosed with either CRS type 1 or CRS type 5. In CRS patients, fat-free mass showed a trend toward representing a protective factor for 6-month mortality (OR=0.904; p=0.06). Also, fat-free mass correlated with HG strength and cardiac ejection fraction. Malnutrition risk was diagnosed in 45% of the patients, whereas 8 patients met the definition of cachexia. Even without statistical significance, CRS patients with malnutrition had lower BMI (Body Mass Index) (p=0.038) and fat-free mass (p= n.s.). However, CRS malnutrition was associated to higher 6-month mortality (p= 0.05), and appears to negatively influence the outcome in CRS (OR= 9; p= 0.06). Our results show that malnutrition is prevalent in CRS patients and influences the clinical outcome. The assessment of nutritional status, and particularly body composition, should be implemented in daily practice of patients with CRS.

Impact of cardio-renal syndrome on adverse outcomes in patients with Fabry disease in a long-term follow-up.

AIMS: Fabry disease (FD) is a rare X-linked lysosomal storage disease with a deficiency of α-galactosidase A leading to progressive sphingolipid accumulation in different organs, among them heart and kidney. We evaluated the impact of cardio-renal syndrome (CRS) on the incidence of major cardiovascular complications and death in a prospective FD cohort. METHODS AND RESULTS: A total of 104 genetically proven FD patients were annually followed at the University Hospitals Zurich and Bern. The main outcome was a composite of incident renal replacement therapy (RRT), hospitalisation due to decompensated Heart Failure, new onset atrial fibrillation, pacemaker/ICD implantation, stroke/TIA and death. Estimated glomerular filtration rate (eGFR) and left ventricular myocardial mass index (LVMMI) where explored as the primary exposure variables. During the median follow-up of 103 [59-155] months, events occurred in 27 patients. In a Cox regression analysis, both higher LVMMI and lower eGFR were independently associated with a greater risk of developing adverse events after adjustment for multiple confounders (HR 1.67 [1.04-2.73] P=0.03 per SD increase in LVMMI, HR 0.45 [0.25-0.83], P=0.01 per SD decrease in eGFR). In patients with CRS, the risk to develop events was significantly increased if adjusted for demographics and RRT (HR 4.46 [1.07-18.62], P=0.04), approaching significance if additionally adjusted for hypertension (HR 4.05 [0.95-17.29], P=0.06). In Kaplan-Meier-Analysis, the poorest event-free survival was observed among patients with CRS. CONCLUSIONS: CRS was associated with a high risk to develop cardiovascular complications and death, emphasizing the importance of its prevention and early recognition. A focus on cardio-reno-protective therapies is crucial.

Continuous Veno-Venous Hemofiltration Improves Survival of Patients With Congestive Heart Failure and Cardiorenal Syndrome Compared to Slow Continuous Ultrafiltration.

Continuous veno-venous hemofiltration (CVVH) could modulate the inflammatory response by removal of circulating cytokines and therefore improve cardiac function in patients with heart failure (HF). We hypothesized that patients with developed cardiorenal syndrome and treated with CVVH have lower risk for mortality than other patients treated with slow continuous ultrafiltration (SCUF). This was a prospective, longitudinal follow-up study for 24 months duration. In total, 120 patients were recruited from the intensive care units. Only patients with cardiorenal syndrome type 1 and 2 were enrolled. 54 CVVH and 23 SCUF patients survived. Mean survival time was longer in CVVH group with cardiomyopathy than in the SCUF group. When we compared patients with cardiomyopathy and hourly urine output <10 mL/h, mean survival time was significantly longer in patients treated with CVVH. This is the first study to analyze the impact of different CRRT modalities (CVVH vs. SCUF) on survival of patients with HF and who developed cardiorenal syndrome. Better survival in patients treated with CVVH, which is mostly pronounced in patients with cardiomyopathy, is a consequence of a better preserved hourly urine output. Longer survival in patients with cardiomyopathy is most probably related to cytokine removal by CVVH with smaller UF rates and longer duration of each treatment. Slow continuous ultrafiltration remains the method of choice in patients with HF and preserved renal function but in cases of developed cardiorenal syndrome is much inferior to CVVH.

Acute kidney injury increases the risk of end-stage renal disease after cardiac surgery in an Asian population: a prospective cohort study.

BACKGROUND: Acute kidney injury (AKI) after cardiac surgery is associated with increased morbidity and mortality. The long-term association between AKI and end-stage renal disease (ESRD) in an Asian population is unknown. Given the high prevalence of diabetes and a younger age of presentation for cardiac surgery, it is important to track this progression of kidney disease. Therefore, we studied the long-term risk of ESRD and mortality in our Asian patients who developed AKI after cardiac surgery. METHODS: With ethics approval, we prospectively recruited 3008 patients who underwent cardiac surgery in Singapore between 2008 and 2012, and followed them up till 2014. ESRD and mortality information were obtained from the Singapore Renal Registry and Singapore Registry of Births and Deaths respectively. AKI was defined using the Acute Kidney Injury Network (AKIN) criteria, and ESRD was defined as stage 5 chronic kidney disease requiring renal replacement therapy. The Cox proportional hazards regression model was used to analyze associations between AKI and the primary outcome of ESRD and the secondary outcome of death. RESULTS: The AKI incidence was 29.1%. During a mean follow-up of 4.4 ± 2.8 years, 0.9% developed ESRD. The hazard ratio (HR) for developing ESRD was 4.7 (95% C.I. = 1.736-12.603, p = 0.002) for AKIN stage 1 patients, and 5.8 (95% C.I. = 1.769-18.732, p = 0.004) for AKIN stage 2 and 3 patients; while the HR for mortality was 1.7 (95% C.I. = 1.165-2.571, p = 0.007) for AKIN stage 1 patients, and 2.5 (95% C.I. = 1.438-4.229, p < 0.001) for AKIN stage 2 and 3 patients. CONCLUSIONS: AKI is associated with ESRD and mortality after cardiac surgery in our Asian population. The trajectory from AKI to ESRD is rapid within 5 years of cardiac surgery. A concerted periodic follow-up assessment is advocated for AKI patients post-cardiac surgery.

The prognostic value of regadenoson SPECT myocardial perfusion imaging in patients with end-stage renal disease.

BACKGROUND: The prognostic value of regadenoson SPECT myocardial perfusion imaging (MPI) has not been specifically studied in patients with end-stage renal disease (ESRD). METHODS AND RESULTS: We prospectively followed ESRD patients enrolled in the ASSUAGE and ASSUAGE-CKD trials in which they received regadenoson-stress 99mTc-tetrofosmin SPECT-MPI. Images were semiquantitatively analyzed by an investigator blinded to clinical and outcome data. Patients were followed for cardiac death, myocardial infarction (MI), and coronary revascularization (CR). Revascularizations occurring >90 days post-MPI were considered "late" events. Survival analysis was performed using Cox regression models, adjusting for age, gender, diabetes, dyslipidemia, smoking, and known coronary artery disease. We analyzed 303 patients (mean age 54 years; 64% men), who were followed for 35 ± 10 months. Adjusting for clinical covariates, abnormal regadenoson-stress MPI (SSS ≥ 4) was associated with increased risk of the composite of cardiac death or MI (23.9% vs 14.4%; HR 1.88; CI 1.04-3.41; P = .037) and the composite of cardiac death, MI, or late CR (27.3% vs 16.7%; HR 1.80; CI 1.03-3.14; P = .039). Adjusting for clinical covariates, regadenoson-induced myocardial ischemia (SDS ≥ 2) was associated with increased rate of the composite endpoint of cardiac death, MI, or CR (33.3% vs 16.9%; HR 1.97; CI 1.19-3.27; P = .008). CONCLUSION: Regadenoson-stress SPECT-MPI provides a significant prognostic value in patients with ESRD. ESRD patients with normal SPECT-MPI have relatively high adverse event rates.

N-acteyl-ß-D-glucosaminidase and kidney injury molecule-1: New predictors for long-term progression of chronic kidney disease in patients with heart failure.

AIM: Patients with chronic heart failure (CHF) are often characterized by the cardiorenal syndrome (CRS). The aim of the present study was to assess whether novel markers of kidney injury are able to predict progression of chronic kidney disease (CKD) in patients with CHF. METHODS: New renal biomarkers, N-acteyl-ß-D-glucosaminidase (NAG), kidney injury molecule-1 (KIM-1) and Neutrophil Gelatinase-Associated Lipocalin (NGAL), were assessed from urine samples of 149 patients with chronic heart failure. During a 5-year-follow-up, renal function was assessed by creatinine and estimated glomerular filtration rate (eGFR CKD EPI) and was available for 138 patients. Further, data regarding all-cause mortality was obtained. RESULTS: Twenty-six patients (18.8%) developed a progression of CKD during the follow-up period, as defined by decline in eGFR category accompanied by a ≥25% drop in eGFR form baseline. No difference regarding age, sex, body mass index, hypertension, diabetes or EF was present between patients with and without CKD progression (each P = n.s.). At baseline, creatinine concentrations and eGFR were significantly different between both groups (sCr: 1.50 ± 0.67 vs 1.04 ± 0.37, P = < 0.001; eGFR: 47.8 ± 12.3 vs. 77.3 ± 23.5 mL/min per 1.73m(2) , each P < 0.001). In a Kaplan-Meier-analysis, KIM-1 and NAG were significant predictors for CKD progression (both P < 0.05). In Cox regression analysis, NAG > median (OR 3.25,P = 0.013), initial eGFR (OR 0.94, P < 0.001) and diuretic use (OR 3.92, P = 0.001) were independent predictors of CKD progression. Further, KIM-1 and NAG were also independent predictors of a combined endpoint of CKD progression and all-cause mortality by Cox regression analysis (each P < 0.05). The combination of both markers showed additive value regarding both endpoints. NGAL showed no association with CKD progression. CONCLUSIONS: During long-term follow-up chronic heart failure patients with CKD show a relevant disease progression. The current study emphasizes a strong association of the tubular biomarkers NAG and KIM-1 with CKD progression in chronic heart failure and suggests their usefulness as cardiorenal markers.

Cardiac biomarkers and acute kidney injury after cardiac surgery.

OBJECTIVES: To examine the relationship of cardiac biomarkers with postoperative acute kidney injury (AKI) among pediatric patients undergoing cardiac surgery. METHODS: Data from TRIBE-AKI, a prospective study of children undergoing cardiac surgery, were used to examine the association of cardiac biomarkers (N-type pro-B-type natriuretic peptide, creatine kinase-MB [CK-MB], heart-type fatty acid binding protein [h-FABP], and troponins I and T) with the development of postoperative AKI. Cardiac biomarkers were collected before and 0 to 6 hours after surgery. AKI was defined as a ≥ 50% or 0.3 mg/dL increase in serum creatinine, within 7 days of surgery. RESULTS: Of the 106 patients included in this study, 55 (52%) developed AKI after cardiac surgery. Patients who developed AKI had higher median levels of pre- and postoperative cardiac biomarkers compared with patients without AKI (all P < .01). Preoperatively, higher levels of CK-MB and h-FABP were associated with increased odds of developing AKI (CK-MB: adjusted odds ratio 4.58, 95% confidence interval [CI] 1.56-13.41; h-FABP: adjusted odds ratio 2.76, 95% CI 1.27-6.03). When combined with clinical models, both preoperative CK-MB and h-FABP provided good discrimination (area under the curve 0.77, 95% CI 0.68-0.87, and 0.78, 95% CI 0.68-0.87, respectively) and improved reclassification indices. Cardiac biomarkers collected postoperatively did not significantly improve the prediction of AKI beyond clinical models. CONCLUSIONS: Preoperative CK-MB and h-FABP are associated with increased risk of postoperative AKI and provide good discrimination of patients who develop AKI. These biomarkers may be useful for risk stratifying patients undergoing cardiac surgery.

The additive burden of iron deficiency in the cardiorenal-anaemia axis: scope of a problem and its consequences.

AIMS: Iron deficiency (ID), anaemia, and chronic kidney disease (CKD) are common co-morbidities in chronic heart failure (CHF) and all independent predictors of unfavourable outcome. The combination of anaemia and CKD in CHF has been described as the cardiorenal-anaemia syndrome. However, the role of ID within this complex interplay of co-existing pathologies is unclear. METHODS AND RESULTS: We studied the clinical correlates of ID (defined as ferritin <100 µg/L or 100-299 µg/L in combination with a transferrin saturation <20%, anaemia) and renal dysfunction (defined as estimated glomerular filtration rate <60 mL/min/1.73 m(2) ) and their prognostic implications in an international pooled cohort, comprising 1506 patients with CHF. Mean age was 64 ± 13 years, 74.2% were male, and 47.3% were in NYHA functional class III. The presence of ID, anaemia, CKD, or a combination of these co-morbidities was observed in 69.3% of the patients. During a median (Q1-Q3) follow-up of 1.92 years (1.18-3.26 years), 440 patients (29.2%) died. Eight-year survival rates decreased significantly from 58.0% for no co-morbidities to 44.6, 33.0, and 18.4%, for one, two, or three co-morbidities, respectively (P < 0.001). Multivariate hazard models revealed ID to be the key determinant of prognosis, either individually (P = 0.04) or in combination with either anaemia (P = 0.006), CKD (P = 0.03), or both (P = 0.02). CONCLUSIONS: Iron deficiency frequently overlaps with anaemia and/or CKD in CHF. The presence of ID amplifies mortality risk, either alone or in combination with anaemia, CKD, or both, making it a potential viable therapeutic target.

Combined heart-kidney transplant improves post-transplant survival compared with isolated heart transplant in recipients with reduced glomerular filtration rate: Analysis of 593 combined heart-kidney transplants from the United Network Organ Sharing Database.

OBJECTIVE: Criteria for simultaneous heart-kidney transplant (HKTx) recipients are unclear. We characterized the evolution of combined HKTx in the United States over time compared with isolated heart transplantation (HTx) and determined factors maximizing post-transplant survival. We focused on whether a threshold estimated glomerular filtration rate (eGFR) could be identified that justified combined transplantation. METHODS: A supplemented United Network Organ Sharing Dataset identified HTx and HKTx recipients from 2000 to 2010. eGFR was calculated for HTx and recipients were grouped into eGFR quintiles. Time-related mortality was compared among recipients, with multivariable factors sought using Cox proportional hazard regression models. RESULTS: We identified 26,183 HTx recipients, of whom 593 were HKTx recipients. HTx increased modestly over time (3.6%), whereas prevalence of HKTx increased dramatically (147%). Risk-unadjusted survival was similar among HTx recipients (8.4 ± 0.04 years) and HKTx recipients (7.7 ± 0.2 years) (P = .76). Isolated HTx recipients in the lowest eGFR quintile had decreased survival (P < .001), but those in the third eGFR quintile had superior survival, suggesting a benefit in this subgroup. HTx recipients in the lowest eGFR quintile (eGFR less than mean 37 mL/minute) had worse survival than combined HKTx recipients (7.1 ± 0.07 vs 7.7 ± 0.2; P < .001). Multivariable factors for increased mortality among HTx recipients included lower eGFR, higher recent panel reactive antibody score, older age, African American race, diabetes, longer ischemic time, and certain diagnoses. CONCLUSIONS: Performance of combined HKTx is increasing out of proportion to isolated HTx. eGFR is an important determinant of improved HTx survival. Combined HKTx recovers post-transplant survival in patients with eGFR <37 mL/minute and can be recommended in this subgroup.

Markers of renal function and acute kidney injury in acute heart failure: definitions and impact on outcomes of the cardiorenal syndrome.

AIMS: Acute kidney injury (AKI) in patients hospitalized for acute heart failure (AHF) is part of the cardiorenal syndrome and has been associated with increased morbidity and mortality. However, definitions and prognostic impact of AKI in AHF have been variable. Cystatin C is a prospective new marker of AKI. The objective of this study was to investigate the use of cystatin C as a marker of early AKI in AHF. METHODS AND RESULTS: Patients (n = 292) hospitalized for AHF had measurements of cystatin C on admission and at 48 h. We assessed the incidence of a rise in cystatin C between the two measurements and evaluated the effect of an increase in cystatin C on outcomes up to 12 months. The population was on average 75 years old and 49% were female. On admission, median cystatin C was 1.25 mg/L (interquartile range 0.99-1.61 mg/L). A rise in cystatin C by >0.3 mg/L within 48 h after hospitalization (AKI(cysC)) occurred in 16% of patients and resulted in 3 days (P = 0.01) longer hospital stay and was associated with significantly higher in-hospital mortality, odds ratio 4.0 [95% confidence intervals (CI) 1.3-11.7, P = 0.01]. During follow-up, AKI(cysC) was an independent predictor of 90 days mortality, adjusted odds ratio 2.8 (95% CI 1.2-6.7, P = 0.02). CONCLUSION: Cystatin C appears to be a useful marker of early AKI in patients hospitalized for AHF. A decline in renal function detected by cystatin C during the first 48 h after hospitalization occurs frequently in AHF and has a detrimental impact on prognosis.