Diagnosis Of Cardiorenal Syndrome Research Articles

Bioinformatics analysis of the microRNA genes associated with type 2 cardiorenal syndrome

BackgroundMicroRNAs (miRNAs) are important regulatory factors in the normal developmental stages of the heart and kidney. However, it is currently unclear how miRNA is expressed in type 2 cardiorenal syndrome (CRS). This study aimed to detect the differential expression of miRNAs and to clarify the main enrichment pathways of differentially expressed miRNA target genes in type 2 CRS.MethodsFive cases of healthy control (Group 1), eight of chronic heart failure (CHF, Group 2) and seven of type 2 CRS (Group 3) were enrolled, respectively. Total RNA was extracted from the peripheral blood of each group. To predict the miRNA target genes and biological signalling pathways closely related to type 2 CRS, the Agilent miRNA microarray platform was used for miRNA profiling and bioinformatics analysis of the isolated total RNA samples.ResultsAfter the microarray analysis was done to screen for differentially expressed circulating miRNAs among the three different groups of samples, the target genes and bioinformatic pathways of the differential miRNAs were predicted. A total of 38 differential miRNAs (15 up- and 23 down-regulated) were found in Group 3 compared with Group 1, and a total of 42 differential miRNAs (11 up- and 31 down-regulated) were found in Group 3 compared to Group 2. According to the Gene Ontology (GO) function and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis, the top 10 lists of molecular functions, cellular composition and biological processes, and the top 30 signalling pathways of predicted gene targets of the differentially expressed miRNAs were discriminated among the three groups.ConclusionBetween the patients with CHF and type 2 CRS, miRNAs were differentially expressed. Prediction of target genes of differentially expressed miRNAs and the use of GO function and KEGG pathway analysis may reveal the molecular mechanisms of CRS. Circulating miRNAs may contribute to the diagnosis of CRS, and further and larger studies are needed to enhance the robustness of our findings.

Pathophysiological Mechanisms and Advances in Diagnosis and Treatment of Cardiorenal Syndrome: A Comprehensive Review

Cardiorenal syndrome (CRS) is a syndrome in which acute and chronic functional abnormalities occur in one organ of the heart and kidney, leading to acute and chronic functional abnormalities in the other organ.The clinical diagnosis and treatment of CRS has its own specificity, and its pathophysiological mechanism is relatively complex.This paper provides an overview of the pathophysiological mechanism of CRS, the speciality of diagnosis and treatment of CRS, and progress in the target of injury markers in order to provide new ideas for clinical treatment. This paper summarizes the pathophysiology and pathogenesis of CRS, its diagnosis and treatment, and the progress of damage marker targets, in order to provide new ideas for clinical treatment.

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.

Cardiorenal Syndrome: A Literature Review.

Cardiorenal syndrome (CRS) is a condition characterized by the intricate two-way relationship between the heart and kidneys, which can lead to acute or chronic dysfunction in these organs. The interplay between cardiorenal connectors and both hemodynamic and non-hemodynamic factors is crucial to understanding this syndrome. The clinical importance of these interactions is evident in the changes observed in hemodynamic factors, neurohormonal markers, and inflammatory processes. Identifying and understanding biomarkers associated with CRS is valuable for early detection and enabling intervention before significant organ dysfunction occurs. This comprehensive review focuses on the clinical significance of biomarkers in the diagnosis, prognosis, and management of CRS. Finally, it highlights the necessity for further advancements in managing this condition.

#2724 THROMBO-INFLAMMATORY BIOMARKERS OF CARDIORENAL SYNDROME IN PATIENTS UNDERGOING MAINTENANCE HEMODIALYSIS IN END STAGE RENAL DISEASE

Abstract Background and Aims Cardiovascular disease is a highly common complication in patients with end stage renal disease (ESRD) on maintenance hemodialysis. In the ESRD patient population, cardiovascular mortality is 20 times higher compared to the general population. The strong relationship of both illnesses can be explained through cardiorenal syndrome (CRS). CRS encompasses a spectrum of disorders involving both the heart and kidneys in which acute or chronic dysfunction in one organ may induce similar effect in the other organ. The diagnosis, prognosis and risk stratification of CRS is poorly understood. Current literature reveals that inflammation and thrombosis are integral to CRS development and key cardiac and renal biomarkers are elevated in CRS patients. Hence, this study aims to demonstrate that thrombo-inflammatory biomarkers and laboratory parameters give a telling narrative of ESRD progression to CRS. Method Plasma samples were collected from 95 ESRD patients which were recruited with an approved IRB protocol at Loyola University Medical Center hemodialysis unit. Normal human plasma (NHP) was obtained from a commercial source (George King Biomedical, Overland Park, KS). Thrombo-inflammatory biomarkers, including Annexin V, MPO, Troponin, L-FABP, VEGF, D-dimer, TNF-alpha, IL-6, CRP, eNOS, Nitrotyrosine, MDA, NEFA, NO, vWF and MCP-1 were measured using commercially available ELISA methods. Cardiovascular comorbidities and laboratory parameters were obtained from EPIC chart analysis. Results were then statistically analyzed using GraphPad Prism v.9; the results were compiled into mean ± SEM, percent change comparison to NHP, analyzed for significance. Results Several cardiovascular comorbidities were seen in the 95 ESRD patient samples including AF (22%), PAD (29%), HF (24%), CAD (22%), DVT (15%), COPD (6.5%), and PE (5.3%). Overall, 25% of the ESRD patients have CRS. Laboratory parameters, ferratin (521.99 ±289.33) and PTH (442.91 ± 1.50) were elevated in ESRD patients. Most of the thrombo-inflammatory CRS biomarkers were elevated in ESRD patients. Biomarkers including Annexin V (ESRD 7.57 ± 5.24, 23.64% vs. 6.125 ± 8.29, p< 0.001), L-FABP (106599.43 ± 176728.97, 1983% vs. 5116.33 ± 1767.88, p<0.0001), D-dimer (ESRD 1447.01 ± 2103, 650.53% vs. 192.8 ± 212.9, p<0.0001), TNF-alpha (ESRD 2.52 ± 1.06, 35.87% vs. 1.85 ± 1.20, p<0.0001), IL-6 (ESRD 5.211 ± 10.36, 317.21% vs. 1.25 ± 1.24, p <0.0001), CRP (ESRD 14.53 ± 14.11, 2214.43% vs. 0.63 ± 0.99, p< 0.0001), NO (ESRD 34.74 ± 19.74, 151.74% vs. 13.8 ± 5.60, p<0.0001), vWF (ESRD 200.7 ± 25.89, 183.03% vs. 70.91 ± 23.13 p< 0.0001) and MCP-1 (148.4 ± 56.09, 67.49% vs. 88.6 ± 27.25, p<0.0001) showed significant increase when compared to NHP. Conclusion This study suggests that thrombo-inflammatory biomarkers and laboratory parameters may be helpful in indicating CRS in ESRD patients. Ultimately, these biomarkers can now be readily used to correlate against other biomarker findings and studied further to determine their accuracy in prognosis and diagnosis of CRS.

Renal Biomarkers in Cardiovascular Patients with Acute Kidney Injury: A Case Report and Literature Review.

Biomarkers have become important tools in the diagnosis and management of cardiorenal syndrome (CRS), a complex condition characterized by dysfunction in both the cardiovascular and renal systems. Biomarkers can help identify the presence and severity of CRS, predict its progression and outcomes, and facilitate personalized treatment options. Several biomarkers, including natriuretic peptides, troponins, and inflammatory markers, have been extensively studied in CRS, and have shown promising results in improving diagnosis and prognosis. In addition, emerging biomarkers, such as kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin, offer potential for early detection and intervention of CRS. However, the use of biomarkers in CRS is still in its infancy, and further research is needed to establish their utility in routine clinical practice. This review highlights the role of biomarkers in the diagnosis, prognosis, and management of CRS, and discusses their potential as valuable clinical tools for personalized medicine in the future.

Heart Failure and Cardiorenal Syndrome: A Narrative Review on Pathophysiology, Diagnostic and Therapeutic Regimens-From a Cardiologist's View.

In cardiorenal syndrome (CRS), heart failure and renal failure are pathophysiologically closely intertwined by the reciprocal relationship between cardiac and renal injury. Type 1 CRS is most common and associated with acute heart failure. A preexistent chronic kidney disease (CKD) is common and contributes to acute kidney injury (AKI) in CRS type 1 patients (acute cardiorenal syndrome). The remaining CRS types are found in patients with chronic heart failure (type 2), acute and chronic kidney diseases (types 3 and 4), and systemic diseases that affect both the heart and the kidney (type 5). Establishing the diagnosis of CRS requires various tools based on the type of CRS, including non-invasive imaging modalities such as TTE, CT, and MRI, adjuvant volume measurement techniques, invasive hemodynamic monitoring, and biomarkers. Albuminuria and Cystatin C (CysC) are biomarkers of glomerular filtration and integrity in CRS and have a prognostic impact. Comprehensive "all-in-one" magnetic resonance imaging (MRI) approaches, including cardiac magnetic resonance imaging (CMR) combined with functional MRI of the kidneys and with brain MRI are proposed for CRS. Hospitalizations due to CRS and mortality are high. Timely diagnosis and initiation of effective adequate therapy, as well as multidisciplinary care, are pertinent for the improvement of quality of life and survival. In addition to the standard pharmacological heart failure medication, including SGLT2 inhibitors (SGLT2i), renal aspects must be strongly considered in the context of CRS, including control of the volume overload (diuretics) with special caution on diuretic resistance. Devices involved in the improvement of myocardial function (e.g., cardiac resynchronization treatment in left bundle branch block, mechanical circulatory support in advanced heart failure) have also shown beneficial effects on renal function.

Cardiorenal Syndrome: New Pathways and Novel Biomarkers.

Cardiorenal syndrome (CRS) is a multi-organ disease characterized by the complex interaction between heart and kidney during acute or chronic injury. The pathogenesis of CRS involves metabolic, hemodynamic, neurohormonal, and inflammatory mechanisms, and atherosclerotic degeneration. In the process of better understanding the bi-directional pathophysiological aspects of CRS, the need to find precise and easy-to-use markers has also evolved. Based on the new pathophysiological standpoints and an overall vision of the CRS, the literature on renal, cardiac, metabolic, oxidative, and vascular circulating biomarkers was evaluated. Though the effectiveness of different extensively applied biomarkers remains controversial, evidence for several indicators, particularly when combined, has increased in recent years. From new aspects of classic biomarkers to microRNAs, this review aimed at a 360-degree analysis of the pathways that balance the kidney and the heart physiologies. In this delicate system, different markers and their combination can shed light on the diagnosis, risk, and prognosis of CRS.

Echocardiography is a good way to diagnose and monitor type 1 cardiorenal syndrome in ICU.

Type-one cardiorenal syndrome (CRS) is defined by acute decompensated heart failure leading to secondary acute kidney injury. No study evaluates the reliability of transthoracic echocardiography as a help tool for diagnosis and optimization of CRS. Therefore, the aim of this study was to assess echocardiographic parameters in patients with CRS in the Intensive Care Unit. We conducted an observational, prospective, single-center study in the ICU department of a general hospital. Patients admitted in the ICU and presenting with type 1 CRS were included. Transthoracic echocardiography was performed at baseline and at day end after treatment by the same trained operator for the same patients. We report various echocardiographic indices at these two timepoints. Twenty-seven patients were included. At baseline 96.3% of patients had signs of congestion (IVC dilation >2 cm), 76% had an altered S-wave (<11.5 cm/s), 72.73% had an altered TAPSE (<17 mm), 85.19% had an elevated RV/LV diameter ratio (>0.6). Between baseline and D end, IVC size and, the number of patients with an elevated RV/LV diameter ratio significantly decreased. Weight decreased, whereas natriuresis significantly increased, and the amount of vasopressors support decreased. Diuresis, and S-wave velocity showed non-significant changes. Main echocardiographic findings at baseline in patients with type 1 CRS consist of a right ventricular dysfunction associated an IVC dilation. We report that weight, RV/LV diameter ratio, and IVC diameter might constitute good follow-up parameters to monitor treatment response.

Кардіоренальний синдром: діагностика та лікування

У діагностиці кардіоренального синдрому (КРС) знаходять широке застосування біологічні маркери, що можуть бути використані для ідентифікації патофізіологічної стадії кардіоренального синдрому, оцінки величини ризику, прогнозу та результату, а також моніторування ефективності лікування. Терапія КРС включає призначення діуретиків, вазодилататорів, інгібіторів ангіотензинперетворюючого ферменту, антагоністів рецепторів ангіотензину II, нітратів і серцевих глікозидів. Одним з ефективних методів лікування КРС є застосування методів замісної ниркової терапії.

Cardiorenal Syndrome in Thalassemia Patients

Background: Cardiorenal syndrome (CRS) is a serious condition with high morbidity and mortality. Secondary CRS (type 5 CRS) is characterized by the coexistence of cardiac abnormality and renal dysfunction occurring secondarily to a systemic condition. In thalassemia, a common hematologic disease in Thailand, there is limited information about the prevalence of secondary CRS. Therefore, this study aimed to investigate the prevalence and associated risk factors of secondary CRS in thalassemia patients.Method: In this cross-sectional cohort study, 53 adult thalassemia patients in out-patient clinic of Chiang Mai University Hospital since October 2016 to June 2017 were included. A criterion for diagnosis of secondary CRS is based on a system proposed by Ronco and McCullough. Cardiac abnormalities, assessed by clinical presentation of heart failure, chest X-ray, electrocardiogram, and echocardiogram, included acute or chronic heart failure by using definition from 2016 ESC guideline or structural cardiac abnormalities defined by LV remodeling and dysfunction, diastolic dysfunction, chronic abnormalities in cardiac function or cardiomyopathy. Renal dysfunction is defined by acute kidney injury or chronic kidney according to 2012 KDIGO guidelines. Clinical and laboratory (serum NT-proBNP, spot urine protein, spot urine albumin, spot urine electrolytes, 24-hours urine protein, and 24-hour urine electrolytes) data for 2 consecutive visits, at least three months apart, were assessed. We analyzed correlation between patients with and without cardiorenal syndrome by Chi-square for categorical data, T-test and non-parametric test of 2 independent samples for continuous data. We used binary logistic regression model for multivariate analysis.Result: Of 53 thalassemia patients [42 (79.2%) transfusion dependent thalassemia and 11 (20.8%) non-transfusion dependent thalassemia], 16 (30.2%) has secondary CRS. Cardiac abnormalities was detected in 23 patients (43.4%), included acute or chronic heart failure (N=4, 7.5%), or structural cardiac abnormalities (N=23, 43.4%). Thirty-one patients (58.5%) had renal abnormalities. Compared with the non-CRS group, the CRS group had a significant increase in serum NT-proBNP level [median (range) = 101.4 (79.2-545.1) VS. 64.8 (16.7-281.2) ng/ml, p=0.05], 24-hours urine magnesium level [mean (95%CI) = 5.98 (3.91-8.04) VS. 4.42 (3.01-5.83) mEq/24 hr., p=0.042], 24-hours urine protein level [median (range) = 249 (132-1610) VS. 161 (77-324) mg/24 hr., p=0.003], and 24-hours urine albumin level [median (range) = 45 (3-1303) VS. 5 (2-184) mg/24 hr., p=0.006], but significance lower in mean arterial pressure (MAP) [mean (95%CI) = 72.7(67.5-77.8) VS. 79.5(69.8-89.2) mmHg, p=0.041]. In univariate analysis, CRS was associated with pulmonary hypertension (OR 2.33, p=0.019), presence of extramedullary hematopoiesis (EMH) (OR 3.79, p=0.03). Multivariate analysis confirmed the association of cardiorenal syndrome with presence of EMH (OR 6.55, p=0.04), lower MAP (OR 0.869, p=0.012), elevated serum NT-proBNP (OR =1.013, p=0.012), and elevated 24-hour urine magnesium (OR 2.17, p=0.004). There was no correlation of CRS with type of thalassemia, serum ferritin, liver iron concentration, cardiac T2* and type of iron chelating agents.Conclusion: This study has demonstrated that CRS is common in thalassemia patients. Patients with the presence of EMH, low MAP, increased 24-hour urine magnesium level or an elevated serum NT-proBNP level are at high risk for developing CRS. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Deciphering key genes in cardio-renal syndrome using network analysis.

Cardio-renal syndrome (CRS) is a rapidly recognized clinical entity which refers to the inextricably connection between heart and renal impairment, whereby abnormality to one organ directly promotes deterioration of the other one. Biological markers help to gain insight into the pathological processes for early diagnosis with higher accuracy of CRS using known clinical findings. Therefore, it is of interest to identify target genes in associated pathways implicated linked to CRS. Hence, 119 CRS genes were extracted from the literature to construct the PPIN network. We used the MCODE tool to generate modules from network so as to select the top 10 modules from 23 available modules. The modules were further analyzed to identify 12 essential genes in the network. These biomarkers are potential emerging tools for understanding the pathophysiologic mechanisms for the early diagnosis of CRS. Ontological analysis shows that they are rich in MF protease binding and endo-peptidase inhibitor activity. Thus, this data help increase our knowledge on CRS to improve clinical management of the disease.

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.

Biomarkers and echocardiography for evaluating the improvement of the ventricular diastolic function after surgical relief of hydronephrosis.

The pathophysiology of cardio-renal syndrome (CRS) is complex. Hydronephrosis caused by urolithiasis may cause cytokine release and lead to cardiac dysfunction. The aim of this study was to evaluate cardiac function changes observed in patients who received double J placement using feasible biomarkers and echocardiography. This was a prospective, single-center study. Eighty-seven patients who presented with acute unilateral hydronephrosis and received ureteroscope stone manipulation were enrolled. Echocardiography and cytokines were measured on the day of the operation and 24 hours after the procedure. Changes before and after surgery were assessed by the paired t-test and Wilcoxon test. Correlation analyses between echocardiographic diastolic indices and cytokine levels were performed using Pearson’s correlation coefficients. Patients with hydronephrosis showed a higher left atrium volume index (LAVI), decreased E', and increased E/ E' ratio, which indicated diastolic dysfunction. Patients with hydronephrosis also exhibited decreased global strain rates during isovolumetric relaxation (SRIVR) and E/ SRIVR, which confirmed the diastolic dysfunction. Significant reductions in LAVI, increases in SRIVR and decreases in E/ SRIVR were observed after the operation. Biomarkers, such as TGF-β and serum NT-proBNP, were significantly decreased after surgery. In addition, a significant correlation was observed between the post-surgical decrease in TGF-β1 and increase in SRIVR. Unilateral hydronephrosis causes cardiac diastolic dysfunction, and relieving hydronephrosis could improve diastolic function. Improvements in cardiac dysfunction can be evaluated by echocardiography and measuring cytokine levels. The results of this study will inform efforts to improve the early diagnosis of CRS and prevent further deterioration of cardiac function when treating patients with hydronephrosis.

Akute kardiorenale Syndrome

Heart and kidney are closely interacting organs which function interdependently. Organ crosstalk between these two organs is based on humoral regulation and by inflammatory mediators, which are similar to those dominating systemic inflammation syndrome. The close interaction between heart and kidney results in organ dysfunction following both chronic and acute functional impairment of the respective counterpart. These changes are summarized under the term cardiorenal syndrome (CRS) which is subdivided into 5types. In the setting of emergency medicine and intensive care units, CRS types1 and 3 are the most common. CRS type1 is characterized by acute kidney injury (AKI) developing as aconsequence of acute heart failure. CRS type3 is represented by acute cardiac failure following AKI, often occurring as aconsequence of nephrotoxins. Diagnosis of CRS should preferably be made on basis of the Kidney Disease: Improving Global Outcomes (KDIGO) criteria for the diagnosis and staging of AKI. The cardiac diagnostic workup should include echocardiography, electrocardiogram (ECG), cardiac enzymes, and brain natriuretic peptide (BNP). The therapeutic approach in CRS is primarily aimed at treating the causative organ dysfunction. In case of CRS type3 this means ensuring adequate kidney perfusion, cautious fluid management, and avoiding additional nephrotoxins. In case of diuretic resistant fluid overload, early initiation of extracorporeal fluid removal, preferably by renal replacement therapy, should be considered.

The cardiorenal problem.

Cardiorenal syndrome (CRS) describes the reciprocally detrimental interaction between both acute and chronic cardiac and renal dysfunction. The syndrome is prevalent and carries a high mortality. CRS has five clinical subtypes, which share common pathogenetic mechanisms including neurohumoral and haemodynamic derangements. We describe several serum markers that offer improvements over traditional measurement of serum creatinine for the diagnosis of CRS. The mainstay of therapy of CRS is loop diuretics in the acute setting and ACE-inhibition in the chronic setting, the latter should in most cases continue despite therapy-associated increases in creatinine. Extracorporeal therapies remain second line treatment.

Cardiorenal syndrome in acute decompensated heart failure

Cardiorenal syndrome (CRS) commonly occurs during treatment of acute decompensated heart failure (ADHF) and is associated with poor clinical outcome. The pathophysiology of CRS entails a complex interaction between hemodynamic alterations, including reduced renal perfusion, increased venous pressure and activation of multiple neurohormonal systems. Attempts to effectively treat congestion while preserving renal function in ADHF are often met with limited clinical success and often require therapeutic decisions that reflect a compromise between potential benefits and harm. At present, there is no evidence-based intervention specifically targeted at renal function. Recent Phase III randomized trials, using novel agents in patients with ADHF, have largely failed to demonstrate any benefits of therapy on renal and clinical outcomes. Early diagnosis of CRS using novel markers of tubular injury may allow for timely interventions and attenuate progression. Future studies are needed to further elucidate the pathophysiology of this complex syndrome and identify new potential targets for effective evidence-based treatments.

Neutrophil Gelatinase-Associated Lipocalin Curve and Neutrophil Gelatinase-Associated Lipocalin Extended-Range Assay: A New Biomarker Approach in the Early Diagnosis of Acute Kidney Injury and Cardio-Renal Syndrome

Cardio-Renal syndrome (CRS) is a common and complex clinical condition in which multiple causative factors are involved. The time window between renal insult and development of acute kidney injury (AKI) in acute heart failure (AHF) can be varied in different patients and AKI often is diagnosed too late, only when the effects of the insult become evident with a loss or decline of renal function. For this reason, pharmaceutical interventions for AKI that have been shown to be renoprotective or beneficial when tested in experimental conditions do not display similar results in the clinical setting. In most cases patients with AHF are admitted with clinical signs and symptoms of congestion and fluid overload. Loop diuretics, typically used to induce an enhanced diuresis in these congested patients, often are associated with a subsequent significant decrease in glomerular filtration rate and cause a creatinine increase that is apparent within 72 hours. Early detection of AKI is not possible with the use of serum creatinine and there is a need for a timely diagnostic tool able to address renal damage while it is happening. We need to define the diagnosis of both AHF and AKI in the early phases of CRS type 1 by coupling a kidney damage marker such as neutrophil gelatinase-associated lipocalin (NGAL) with B-type natriuretic peptide (BNP). Indeed, it would be ideal to make available a panel including whole blood or plasma cardiac and renal biomarkers building specific, pathophysiologically based, molecular profiles. Based on current knowledge and consensus, we can use kidney damage biomarkers such as plasma NGAL for an early diagnosis of AKI. However, differences in individual patient values and uncertainties about the ideal cut-off values may currently limit the application of these biomarkers. We propose that NGAL may increase its usefulness in the diagnosis and prevention of CRS if a curve of plasma values rather than a single plasma measurement is determined. To apply the concept of measuring an NGAL curve in AHF patients, however, assay performance in the lower-range values becomes a critical factor. For this reason, we propose the use of the new extended-range plasma NGAL assay that may contribute to remarkably improve the sensitivity of AKI diagnosis in AHF and lead to more effective intervention strategies.