Non-cardiac comorbidities in heart failure: an update on diagnostic and management strategies.

Managing non-cardiac comorbidities in heart failure (HF) requires a tailored approach that addresses each patient's specific conditions and needs. Regular communication and coordination among healthcare providers is crucial to providing the best possible care for these patients. Poorly controlled hypertension contributes to left ventricular remodeling and diastolic dysfunction, emphasizing the importance of optimal blood pressure control while avoiding adverse effects. Among HF patients with diabetes, SGLT2 inhibitors and mineralocorticoid receptor antagonists have shown promise in reducing HF-related morbidity and mortality. Chronic kidney disease exacerbates HF and vice versa, forming the vicious cardiorenal syndrome, so disease-modifying therapies should be maintained in HF patients with comorbid CKD, even with transient changes in kidney function. Anemia in HF patients may be multifactorial, and there is growing evidence for the benefit of intravenous iron supplementation in HF patients with iron deficiency with or without anemia. Obesity, although a risk factor for HF, paradoxically offers a better prognosis once HF is established, though developing treatment strategies may improve symptoms and cardiac performance. In HF patients with stroke and atrial fibrillation, anticoagulation therapy is recommended. Among HF patients with sleep-disordered breathing, continuous positive airway pressure may improve sleep quality. Chronic obstructive pulmonary disease often coexists with HF, and many patients can tolerate cardioselective beta-blockers. Cancer patients with comorbid HF require careful consideration of cardiotoxicity risks associated with cancer therapies. Depression is underdiagnosed in HF patients and significantly impacts prognosis. Cognitive impairment is prevalent in HF patients and impacts their self-care and overall quality of life.

The Value of Soluble ST2 in Predicting Cardiorenal Syndrome Type 1 in Acute Myocardial Infarction Patients.

OBJECTIVE: To investigate the predictive value of soluble growth stimulation expressed gene 2 (sST2) for the development of Cardiorenal syndrome type 1 (CRS1) in patients with acute myocardial infarction during hospitalization. METHODS: A retrospective study included 202 patients with acute myocardial infarction, divided into the CRS1 group (n = 61) and the Non-CRS1 group (n = 141) by the CRS1 occurrence. A logistic regression analysis was applied to find independent predictors of the CRS1 occurrence during hospitalization. Receiver operating characteristic (ROC) curves were applied to analyze the predictive values of sST2, N-terminal pro-B type natriuretic peptide (NT-proBNP), and estimated glomerular filtration rate (eGFR). RESULT: The multivariate logistic regression analysis revealed that sST2, NT-proBNP, eGFR, Multivessel coronary artery disease, and diuretic use were independent predictors of the CRS1 occurrence during hospitalization. Application of ROC curve analysis displayed that sST2 had the largest area under the curve (AUC) value of 0.874, sensitivity of 0.770, and specificity of 0.894; sST2, eGFR, and NT-proBNP as combined predictors had an AUC value of 0.908, sensitivity of 0.820, and specificity of 0.908. The ROC curves of sST2 and the combined predictive indices were compared using MedCalc software (version 19.6.3), and no statistically significant difference was found between the two (p = 0.142). The cutoff values of the three indicators were determined by the maximum Youden index. When sST2 ≥61.8 ng/mL, eGFR ≤80.6 mL/min/1.73 m2 and NT-proBNP ≥1525 pg/mL were classified as abnormal range, it was found that more number of abnormal indicators may be more advantageous of risk stratification in CRS1. CONCLUSIONS: sST2 can be used as a novel predictor of the CRS1 occurrence in patients with acute myocardial infarction during hospitalization. sST2, eGFR, and NT-proBNP combined may have better predictive value.

CARDIORENAL SYNDROME AND COVID-19.

The purpose of this paper is to analyses the cases with cardiorenal syndrome, and the ratio of cardiovascular disease and COVID-19. Prospective methods were used to conduct this research, including the period (January 2020-December 2021). Cases of patients treated at the Nephrology Clinic at the University Clinical Center of Kosovo (UCCK) have been studied. The categorical variables were analyzed with the X² test and the Fisher exact test. The study included 120 patients with acute renal disease treated at the Nephrology Clinic at the University Clinical Center of Kosovo (UCCK), of which 46 (38.3%) female and 74 (61.6%) male. Of the 120 patients included in the study 4 were 18-34 years old, 8 were 35-49 years old, 30 were 50-64 years old, and 78 were > 65 years old. There is a strong link between cardiorenal syndrome and age. Regarding cardiorenal syndrome and its association with other diseases in this prospective study were found these concomitant diseases such as: diabetes mellitus type 2, secondary anemia, hypothyroidism, hyperparathyroidism, pneumonia, sepsis, ascites, mesenteric tumor, hyperkalemia, and Covid-19 Infection. There is a strong link between cardiorenal syndrome and COVID-19 Infection. In recent decades various studies have been done against the definition of cardiorenal syndrome, the understanding of pathophysiology, the use of new biomarkers that represent a new dimension in the diagnostic algorithm, and the difficulties in treating this syndrome.

Diagnostic value and utility of commonly used biomarkers of cardiac and renal function in cardiorenal syndromes: a narrative review.

Cardiorenal syndrome (CRS), first defined in 2004 as a consequence of the interactions between the kidneys and other circulatory departments leading to acute heart failure, has since been recognized as a complex clinical entity that is hard to define, diagnose and classify. The framework for the classification of CRS according to pathophysiologic background was laid out in 2008, dividing CRS into five distinct phenotypes. However, determining the timing of individual organ injuries and making a diagnosis of either renal or cardiac failure remains an elusive task. In clinical practice, the diagnosis and phenotyping of CRS is mostly based on using laboratory biomarkers in order to directly or indirectly estimate the degree of end-organ functional decline. Therefore, a well-educated clinician should be aware of the effects that the reduction of renal and cardiac function has on the diagnostic and predictive value and properties of the most commonly used biomarkers (e.g. troponins, N-terminal pro-brain natriuretic peptide, serum creatinine etc). They should also be acquainted, on a basic level, with emerging biomarkers that are specific to either the degree of glomerular integrity (cystatin C) or tubular injury (neutrophil gelatinase-associated lipocalin). This narrative review aims to provide a scoping overview of the different roles that biomarkers play in both the diagnosis of CRS and the prognosis of the disease in patients who have been diagnosed with it, along with highlighting the most important pitfalls in their interpretation in the context of impaired renal and/or cardiac function.

Recent Developments in the Evaluation and Management of Cardiorenal Syndrome: A Comprehensive Review.

Cardiorenal syndrome (CRS) is an increasingly recognized diagnostic entity associated with high morbidity and mortality among acutely ill heart failure (HF) patients with acute and/ or chronic kidney diseases (CKD). While traditionally viewed as a state of decline in glomerular filtration rate (GFR) due to decreased renal perfusion, mainly due to therapeutic interventions to relieve congestive in HF, recent insights into the underlying pathophysiologic mechanisms of CRS led to a broader definition and further classification of CRS into 5 distinct types. In this comprehensive review, we discuss the classification of CRS, highlighting the underlying common pathogenetic pathways of heart failure and kidney injury, including increased congestion, neurohormonal dysregulation, oxidative stress as well as inflammation, and cytokine storm that are particularly evident in COVID-19 patients with multiorgan failure and also in those with other disorders including sepsis, systemic lupus erythematosus and amyloidosis. In this review we also present the recent advances in the diagnostic strategies of CRS including cardiac and renal biomarkers as well as advanced cardiac and renal imaging techniques that are available to aid in the diagnosis as well as in the prognostication of this disorder. Finally, we discuss the various therapeutic options available to-date, including fluid optimization, hemofiltration, renal replacement therapy as well as the role of SGLT2 inhibitors in light of recent data from RCTs. It is important to note that, CRS population are either excluded or underrepresented, at best, in major RCTs and therefore, therapeutic recommendations are largely extrapolated from HF and CKD clinical trials.

Cystatin C as a biomarker for cardiorenal syndrome diseases quantitative diagnostics and monitoring via point-of-care.

With heart failure (HF) and renal malfunction becoming global public health issues, there is an urgent need to monitor diseases at home or in the community. Point-of-care testing (POC) would shorten the patients waiting time compared with laboratory molecular analysis. This work evaluates two types of gold nanomaterials, and two assay protocols, to develop a lateral flow (LF) system for Cystatin C (CysC) quantification. Of the protocols, the 'delayed-release' shows the alleviation of the hook effects with 1% BSA running buffer (RB), albeit at increased complexity with three steps of washing. The standard method with sample dilution (1: 150 sample dilution for GNPs, and 1:10 sample dilution for GNRs) can ensure the clinical range detection of CysC as 1 mg/L with partial LF assays. GNPs have stronger optical signal intensity compared with GNRs and developed full LF assays with GNPs require 1:1.5 sample dilution in recombinant Cys C detection. The ideal sample dilution ratio is different for partial and full LF assays. Clinical Relevance- This work is the basis of future work that will use LF devices for human serum/plasma monitoring to assess kidney function related to heart failure during medication. The specificity, sensitivity, and limit of detection will be validated via a clinical trial before potential clinical use.

Association of Nephronophthisis 4 genetic variation with cardiorenal syndrome and cardiovascular events in Japanese general population: the Yamagata (Takahata) study.

BACKGROUND: Nephronophthisis (NPHP) 4 gene encoding nephrocystin-4, which contributes to end-stage renal disease in children and young adults, is involved in the development of the heart and kidneys. Cardiorenal syndrome (CRS), which consists of bidirectional dysfunction of the heart and kidneys, is a risk factor for cardiovascular events. Single-nucleotide polymorphisms (SNPs) within the NPHP4 gene are reportedly associated with kidney function, even in adults. However, the association of NPHP4 gene variability with CRS and cardiovascular events remains unknown. METHODS AND RESULTS: This prospective cohort study included 2946 subjects who participated in a community-based health study with a 16-year follow-up period. We genotyped 11 SNPs within the NPHP4 gene whose minor allele frequency was greater than 0.1 in the Japanese population. The SNP rs12058375 was significantly associated with CRS and cardiovascular events. Multivariate logistic analysis demonstrated a significant association between the homozygous A-allele of rs12058375 with the presence of CRS. Haplotype analysis identified the haplotype with the A-allele of rs12058375 as an increased susceptibility factor for CRS. Kaplan-Meier analysis demonstrated that homozygous A-allele carriers of rs12058375 had the greatest risk of developing cardiovascular events among the NPHP4 variants. Multivariate Cox proportional hazard regression analysis revealed that the homozygous A-allele and heterozygous carriers of rs12058375 were associated with cardiovascular events after adjusting for confounding factors. The net reclassification index and integrated discrimination index were significantly improved by the addition of rs12058375 as a cardiovascular risk factor. CONCLUSION: Genetic variations in the NPHP4 gene were associated with CRS and cardiovascular events in the general population, suggesting that it may facilitate the early identification of high-risk subjects with CRS and cardiovascular events.

Nicorandil Decreases Renal Injury in Patients With Coronary Heart Disease Complicated With Type I Cardiorenal Syndrome.

ABSTRACT: Cardiorenal syndrome (CRS) is a group of disorders in which heart or kidney dysfunction worsens each other. This study aimed to explore the improvement effect of nicorandil on cardiorenal injury in patients with type I CRS. Patients with coronary heart disease complicated with type I CRS were enrolled. Based on the conventional treatment, the patients were prospectively randomized into a conventional treatment group and a nicorandil group, which was treated with 24 mg/d nicorandil intravenously for 1 week. Fasting peripheral venous blood serum and urine were collected before and at the end of treatment. An automatic biochemical analyzer and enzyme linked immunosorbent assay were used to detect B-type brain natriuretic peptide (BNP), serum creatinine (Scr) and cystatin C (Cys-C), renal injury index-kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and interleukin-18 (IL-18) levels. The left ventricular ejection fraction was measured by echocardiography. All measurements were not significantly different between the nicorandil and conventional treatment groups before treatment (all P > 0.05), and BNP, Scr, Cys-C, NGAL, KIM-1, and IL-18 were decreased in the 2 groups at the end of treatment (all P < 0.05). Compared with the conventional treatment group, BNP, Scr, Cys-C, NGAL, KIM-1, and IL-18 were more significantly decreased in the nicorandil group (all P < 0.05) and left ventricular ejection fraction was more significantly increased (P < 0.05). Therefore, nicorandil could significantly improve the cardiac and renal function of patients with type I CRS. This may prove to be a new therapeutic tool for improving the prognosis and rehabilitation of type I CRS.

Tyrosine and Tryptophan vibrational bands as markers of kidney injury: a renocardiac syndrome induced by renal ischemia and reperfusion study.

Renal injury caused by renal ischemia and reperfusion strongly influences heart morphology, electrophysiology, and redox unbalance. The so-called cardiorenal syndrome is an important class of dysfunction since heart and kidneys are responsible for hemodynamic stability and organ perfusion through a complex network. In the present work we investigate the vibrational spectral features probed by Fourier-Transform Raman (FT-Raman) spectroscopy due to physiological alterations induced by renal ischemic reperfusion aiming to detect molecular markers related to progression of acute to chronic kidney injury and mortality predictors as well. C57BL/6J mice were subjected to unilateral occlusion of the renal pedicle for 60 min and reperfusion for 5, 8, and 15 days. Biopsies of heart and kidney tissues were analyzed. Our findings indicated that cysteine/cystine, fatty acids, methyl groups of Collagen, α-form of proteins, Tyrosine, and Tryptophan were modulated during renal ischemia and reperfusion process. These changes are consistent with fibroblast growth factors and Collagen III contents changes. Interestingly, Tyrosine and Tryptophan, precursor molecules for the formation of uremic toxins such as indoxyl sulfate and p-cresyl sulfate were also modulated. They are markers of kidney injury and their increase is strongly correlated to cardiovascular mortality. Regarding this aspect, we notice that monitoring the Tyrosine and Tryptophan bands at 1558, 1616, and 1625 cm-1 is a viable and and advantageous way to predict fatality in cardiovascular diseases both "in vivo" or "in vitro", using the real-time, multiplexing, and minimally invasive advantages of FT-Raman spectroscopy.

Evaluation of the diagnostic value of the renal resistive index as a marker of the subclinical development of cardiorenal syndrome in MMVD dogs.

INTRODUCTION: Myxomatous mitral valve disease (MMVD) in dogs inevitably causes renal dysfunction. These interactions are known as the cardiorenal syndrome (CRS). The main aims of the study were to evaluate whether renal resistive index (RRI) may be useful as a non-invasive marker in subclinical stage of kidney injury in dogs with MMVD and to compare RRI with SDMA and Cyst C. METHODS: Forty-four dogs were divided into two groups: control-15 healthy dogs and the heart group-29 dogs with MMVD (ACVIM class Cc). Study protocol included: anamnesis, clinical examination, electrocardiography, echocardiography, chest radiography, abdominal ultrasonography with measurements of the renal resistive index (RRI), urine, and blood analysis. RESULTS: The RRI in the heart group was significantly higher 0.725 ± 0.035 versus control group 0.665 ± 0.028 (p < 0.00085). The RRI cut-off point in dogs with stable chronic heart failure (CHF) under 8 years is 0.775, in older 0.64. RRI was similar in MMVD dogs treated with ACE-I + furosemide and dogs treated ACE-I + torasemide + pimobendan + spironolactone. There was no correlation between RRI and SDMA or Cyst C. CONCLUSION: RRI is more sensitive than creatinine, SDMA and Cyst C to reveal kidney injury in MMVD dogs class Cc younger than 8 years.

Síndrome Cardiorrenal Aguda: Qual Critério Diagnóstico Utilizar e sua Importância para o Prognóstico? / Acute Cardiorenal Syndrome: Which Diagnostic Criterion to Use And What is its Importance for Prognosis?

Resumo A indefinição de critérios diagnósticos para síndrome cardiorrenal aguda (SCRA) impacta em diferentes resultados prognósticos. Objetivou-se avaliar os critérios diagnósticos da SCRA e o impacto no prognóstico. Procedeu-se à revisão sistemática utilizando-se a metodologia PRISMA e os critérios PICO nas bases MEDLINE, EMBASE e LILACS. A pesquisa incluiu artigos originais do tipo ensaio clínico, coorte, caso-controle e meta-análises publicados no período de janeiro de 1998 até junho de 2018. Não foi encontrada na literatura nem nas diretrizes de insuficiência cardíaca uma definição clara dos critérios diagnósticos da SCRA. O critério diagnóstico mais comumente utilizado é o aumento da creatinina sérica de pelo menos 0,3 mg/dl em relação à basal. Entretanto, existem controvérsias na definição de creatinina basal e de qual deveria ser a creatinina sérica de referência dos pacientes críticos. Esta revisão sistemática sugere que os critérios de SCRA devem ser revistos para que se inclua o diagnóstico de SCRA na admissão hospitalar. A creatinina sérica de referência deve refletir a função renal basal antes do início da injúria renal aguda.

Abstract The absence of a consensus about the diagnostic criteria for acute cardiorenal syndrome (ACRS) affects its prognosis. This study aimed at assessing the diagnostic criteria for ACRS and their impact on prognosis. A systematic review was conducted using PRISMA methodology and PICO criteria in the MEDLINE, EMBASE and LILACS databases. The search included original publications, such as clinical trials, cohort studies, case-control studies, and meta-analyses, issued from January 1998 to June 2018. Neither literature nor heart failure guidelines provided a clear definition of the diagnostic criteria for ACRS. The serum creatinine increase by at least 0.3 mg/dL from baseline creatinine is the most used diagnostic criterion. However, the definition of baseline creatinine, as well as which serum creatinine should be used as reference for critical patients, is still controversial. This systematic review suggests that ACRS criteria should be revised to include the diagnosis of ACRS on hospital admission. Reference serum creatinine should reflect baseline renal function before the beginning of acute kidney injury.

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.

Evaluation of Tryptic Podocin Peptide in Urine Sediment Using LC-MS-MRM Method as a Potential Biomarker of Glomerular Injury in Dogs with Clinical Signs of Renal and Cardiac Disorders.

The early asymptomatic stage of glomerular injury is a diagnostic challenge in the course of renal and extra-renal disease, e.g., heart insufficiency. It was found that podocin, a podocyte-specific protein present in the urine, may serve as a biomarker in the diagnosis of glomerular disease in humans and animals including glomerulonephritis, glomerulosclerosis, amyloidosis, or nephropathy. Therefore, there is a need of development of the sensitive and straightforward method of urinary podocin identification. In this work, we report our extended research under the glomerular injury investigation in dogs by application of clinical examination and LC-MS-MRM method in the identification of canine podocin in urine samples. The LC-MS-MRM method is based on the identification of podocin tryptic peptide with the 218H-AAEILAATPAAVQLR-OH232 sequence. The model peptide was characterized by the highest ionization efficiency of all the proposed model podocin tryptic peptides in a canine urine sediment according to the LC-MS/MS analysis. The obtained results revealed the presence of the model peptide in 40.9% of dogs with MMVD (active glomerular injury secondary to heart disease = cardiorenal syndrome-CRS) and 33.3% dogs with chronic kidney disease. The potential applicability of the developed methodology in the analysis of podocin in canine urine sediments was confirmed.

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.

Plasmon Near-Field Coupling of Bimetallic Nanostars and a Hierarchical Bimetallic SERS "Hot Field": Toward Ultrasensitive Simultaneous Detection of Multiple Cardiorenal Syndrome Biomarkers.

Cardiorenal syndrome (CRS) has posed tremendous challenges in patient management, and the detection of serum biomarkers may provide opportunities for early diagnosis and effective treatment. Herein, we introduce a novel surface-enhanced Raman scattering (SERS)-based sandwich immunoassay platform to simultaneously detect cardiac troponin I (cTnI), N-terminal prohormone of brain natriuretic peptide (NT-ProBNP), and neutrophil gelatinase-associated lipocalin (NGAL) for the early diagnosis of CRS by using Raman reporter-molecule-labeled Ag-Au nanostars (Ag-Au NSs) as nanotags and a three-dimensional ordered macroporous (3DOM) Au-Ag-Au plasmonic array as substrate. The Ag-Au NSs prepared by galvanic replacement feature bimetallic composition and a multibranched structure so that high SERS stability and enhancement are exhibited. Meanwhile, a 3DOM Au-Ag-Au plasmonic array was fabricated through Au-assisted electrodeposition and was further covered by a protective Au layer; it is characterized by a large specific surface area and high homogeneity, serving as a "hot field". When the nanotags and substrate were combined, "hot spots" were generated from the plasmon near-field coupling, which greatly increased the SERS enhancement. The limits of detection (LODs) were 0.76, 0.53, and 0.41 fg mL-1 for cTnI, NT-ProBNP, and NGAL, respectively, and the Raman images indicated the approximate concentration ranges of the detected proteins for visual analysis. Taking advantage of the ultrasensitivity and multiplexing capability of this approach, we further analyzed clinical blood samples with high integrality, efficiency, and accuracy. Therefore, the presented SERS immunoassay platform holds promise as an ideal test method for point-of-care detection and a powerful tool for investigations into the complex CRS-related biological process.

Cardiorenal status using amino-terminal pro-brain natriuretic peptide and cystatin C on cardiac resynchronization therapy outcomes: From the BIOCRT Study.

BACKGROUND: Cardiorenal syndrome comprises a heterogeneous group of disorders characterized by acute or chronic cardiac and renal dysfunction. OBJECTIVE: The purpose of this study was to determine the effect of cardiorenal status using a dual-marker strategy with amino-terminal pro-brain natriuretic peptide (NT-proBNP) and cystatin C on cardiac resynchronization therapy (CRT) outcomes. METHODS: In 92 patients (age 66 ± 13 years; 80% male; left ventricular ejection fraction 26% ± 7%), NT-proBNP and cystatin C levels were measured at CRT implantation and at 1 month. NT-proBNP >1000 pg/mL and cystatin C >1 mg/L were considered high. Baseline cardiorenal patients were defined as having high NT-proBNP and cystatin C. At 1 month, CRT patients were categorized as (1) irreversible cardiorenal if cystatin C was persistently high; (2) progressive cardiorenal with transition from low to high cystatin C; (3) reversible cardiorenal with transition from high to low cystatin C; and (4) "normal" with stable low cystatin C. Outcomes were 6-month clinical and echocardiographic CRT response and 2 -year major adverse cardiovascular event (MACE). RESULTS: Compared to patients with low NT-proBNP and cystatin C, cardiorenal patients had >9-fold increase risk of CRT nonresponse (odds ratio uncompensated 9.0; compensated 36.4; both P ≤.004) and >6-fold risk of MACE (hazard ratio uncompensated 8.5; P = .005). Compared to "normal" and reversible patients (referent), irreversible patients had a 9-fold increase for CRT nonresponse (odds ratio 9.1; P <.001) and had >4-fold risk of MACE (adjusted hazard ratio 5.1; P <.001). Irreversible patients were most likely echocardiographic CRT nonresponders. CONCLUSION: Cardiorenal status by NT-proBNP and cystatin C can identify high-risk CRT patients, and those with both elevated concentrations have worse prognosis.

Type 1 cardiorenal syndrome in a patient with an acute infection caused by Trypanosoma cruzi in the Brazilian Amazon region - a case report

Abstract Cardiorenal syndrome type 1 (CRS 1) occurs when acute heart failure leads to acute kidney injury. There are several etiologies of CRS 1, including Chagas disease. Here, we present the first case report of CRS 1 in a patient with acute Chagas disease. Electrocardiography, transthoracic echocardiography, and cardiac magnetic resonance imaging showed signs of acute myocarditis. Laboratory examination revealed severe loss of kidney function, with a creatinine clearance of 30 mL/min, which fully normalized after treatment. Due to emergence of Chagas disease in the Brazilian Amazon, it is important to report unique clinical features in order to improve patients' outcomes.

Biomarkers for acute cardiorenal syndrome.

Cardiorenal syndromes are disorders of the heart and kidneys whereby dysfunction in one organ may lead to dysfunction in the other organ. Cardiorenal syndrome type I (CRS I) is defined as acute kidney injury caused by acute cardiac dysfunction such as acute decompensated heart failure and acute coronary syndrome. Traditional markers like serum creatinine may delay the diagnosis of acute kidney injury and provide limited information regarding the underlying pathophysiology in the setting of CRS I. Herein, we briefly review some emerging biomarkers, including brain natriuretic peptide, soluble ST2, angiopoietin, soluble thrombomodulin, neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, cystatin C, interleukin-18 and calprotectin. These biomarkers may help early detecting, differential diagnosis, assessing disease severity and prognosis in patients with CRS I, therefore improve patient management and outcomes.

Síndrome cardiorrenal. Una revisión / Cardio-renal syndrome. A review

La presente revisión analiza los síndromes cardiorrenales tipo 1 y 2, que se desarrollan a partir de la afectación cardíaca, siendo el compromiso renal consecuencia de la misma, destacando la profunda interacción entre ambos órganos. Se estudian la epidemiología, la fisiopatología, los aspectos diagnósticos y los pilares del tratamiento de cada uno de ellos, considerando los diferentes ensayos clínicos que aportan la evidencia fundamental para el manejo de los pacientes. Se destacan los diversos factores involucrados en su génesis: hemodinámicos, inflamatorios, neurohumorales, iatrogénicos. Se aborda el cuestionamiento de su existencia como una entidad real, tal como se define y estudia actualmente, quedando planteada la necesidad de progresar en el conocimiento de sus aspectos diagnósticos y terapéuticos. Se destaca finalmente la importancia de desarrollar medidas preventivas del daño que pueda provocar un órgano sobre el otro y de los demás factores involucrados.

This review analyzes the cardio-renal syndromes type 1 and 2, which develop from cardiac involvement with renal involvement being a consequence of it, highlighting the strong interaction between both organs. The epidemiology, the pathophysiology, the diagnostic aspects, and the pillars of the treatment of each of them are studied, considering the different clinical trials that provide the evidence for their management. It highlights the various factors involved in its genesis: hemodynamic, inflammatory, neurohumoral and iatrogenic. The controversy of its existence as a real entity, as it is currently defined and studied, is addressed, and the need to progress in the knowledge of its diagnostic and therapeutic aspects is raised. Finally, the importance of developing preventive measures of damage that one organ may cause over the other and of the other involved factors, is highlighted.

Evaluation of serum neutrophil gelatinase-associated lipocalin as a novel biomarker of cardiorenal syndrome in dogs.

Worsening renal function and azotemia in patients with heart failure (HF) are strongly associated with disease severity and poor prognosis. Increasing interest in this correlation led to the description and classification of cardiorenal syndrome (CRS). We evaluated the role of neutrophil gelatinase-associated lipocalin (NGAL) in the early detection of CRS in dogs with HF. Ten healthy dogs and 31 dogs admitted with HF were included in our study. NGAL and troponin-I were measured on samples collected on the day of admission; creatinine was measured on admission and again on day 7. The CRS group was defined as subsequently developing renal azotemia. Of 31 dogs with HF, 20 were included in the HF group, and 11 were included in the CRS group. The admission NGAL concentrations of the CRS group were significantly higher than those of other groups ( p < 0.001). The severity of HF evaluation based on the modified New York Heart Association classification showed significant correlation with NGAL ( p < 0.001) and troponin-I ( p = 0.009) concentration. However, only serum NGAL concentration at admission was significantly associated with the development of CRS in dogs with HF ( p = 0.021). The admission serum NGAL ≥ 16.0 ng/mL (optimal cutoff value) had a sensitivity of 90.9% and specificity of 90.0% in predicting the development of CRS.