Cardiorenal Syndrome Type Research Articles

Classical and myocardial deformation echocardiographic indices in chronic kidney disease patients; effects of aging and comparison to healthy controls

Abstract Funding Acknowledgements Type of funding sources: None. Background Patients with chronic kidney disease (CKD) are at high risk for cardiovascular disease compared to the general population. Classic echocardiographic indices of left ventricular (LV) function may not be sensitive enough in detecting early myocardial deterioration in CKD patients while LV speckle tracking (2DSTE) analysis has shown promising results. Dipyridamole stress echocardiography (DIPSE), mostly used to measure coronary flow reserve (CFR), assesses coronary macrovascular and/or microvascular dysfunction in a non-invasive way. Purpose To investigate differences in classic, 2DSTE-related indices, CFR and other DIPSE-induced changes in various echocardiographic parameters between 1) healthy controls and age-matched (younger) CKD patients, 2) younger versus older CKD patients with similar clinical characteristics. Methods We prospectively evaluated 30 healthy controls and 60 consecutive CKD patients 40-75 years old who were followed-up at the CKD outpatient clinic of a University Hospital in Western Greece. A standard echocardiographic analysis including 2DSTE analysis was performed in all subjects before and after dipyridamole infusion. CFR in left anterior descending artery was also assessed. Results The median age of the CKD patients was 63 years and most of them were males (70%). Younger patients with CKD (i.e. <60 years old) had higher E/e" ratio (7.80 ± 2.71 vs 6.06 ± 1.37, p = 0.019), LVMI (114.7 ± 41.1 vs 89.6 ± 21.2, p = 0.017) and relative wall thickness (0.47 ± 0.08 vs 0.40 ± 0.06, p = 0.031) and lower E" (10.6 ± 2.6 vs 2.3 ± 2.9 cm/s, p = 0.045) compared to age and gender-matched healthy controls. Older CKD patients had lower E/A (0.80 ± 0.19 vs 1.03 ± 0.33, p = 0.007) and E" (8.5 ± 1.8 vs 10.6 ± 2.6 cm/s, p = 0.003) compared to younger CKD patients. CFR was higher in healthy controls compared to both younger (3.93 ± 1.25 versus 3.1 ± 0.75, p = 0.009) and older CKD patients (3.93 ± 1.25 versus 2.89 ± 0.88, p < 0.001); no significant difference in CFR was observed between younger and older CKD patients. Dipyridamole-induced changes in other studied echocardiographic indices did not differ significantly among groups. Conclusions In the current study, impaired coronary microcirculation, LV diastolic function and increased LV mass with concentric remodeling were shown to be the principal findings early in the process of CKD. These results may have pathophysiological implications for cardiorenal syndrome type 4 and targeted cardiac assessment in CKD patients. Future studies are needed to assess whether any therapeutic efforts aiming to delay or reverse these changes may have an impact on the cardiovascular prognosis in CKD patients.

Renal injury in cardiorenal syndrome type 1 is mediated by albumin.

Cardiorenal syndrome type 1 (CRS‐1) acute kidney injury (AKI) is a critical complication of acute cardiovascular disease but is poorly understood. AKI induces acute albuminuria. As chronic albuminuria is associated with worsening kidney disease and albumin has been implicated in tubular epithelial injury, we investigated whether albumin participates in CRS‐1, and whether CRS‐1 alters renal albumin handling. We report the role of albumin in in vivo and in vitro CRS‐1 models. An established translational model, cardiac arrest and cardiopulmonary resuscitation (CA/CPR) induced severe acute albuminuria which correlated with tubular epithelial cell death. In vivo microscopy demonstrated CA/CPR‐induced glomerular filtration of exogenous albumin, while administration of exogenous albumin after CA/CPR worsened AKI compared to iso‐oncotic control. Increased albumin signal was observed in the proximal tubules of CA/CPR mice compared to sham. Comparison of albumin flux from tubular lumen to epithelial cells revealed saturated albumin transport within minutes of albumin injection after CA/CPR. In vitro, HK2 cells (human kidney tubular epithelial cells), exposed to oxygen‐glucose deprivation were injured by albumin in a dose dependent fashion. This interference was unchanged by the tubular endocytic receptor megalin. In conclusion, CRS‐1 alters albumin filtration and tubular uptake, leading to increased tubular exposure to albumin, which is injurious to tubular epithelial cells, worsening AKI. Our findings shed light on the pathophysiology of renal albumin and may guide interventions such as albumin resuscitation to improve CRS‐1 outcomes. This investigation may have important translational relevance for patients that receive exogenous albumin as part of their CRS‐1 treatment regimen.

Risk Factors and Outcome Variables of Cardiorenal Syndrome Type 1 in Acute Myocardial Infarction Patients.

PurposeThis study’s goal was to explore risk factors affecting short-term prognosis of cardiorenal syndrome type 1 (CRS1) in acute myocardial infarction (AMI) patients.MethodsIn this retrospective analysis of CRS1 in AMI patients hospitalized from January 2011 to December 2014, the patients were classified into deceased or survivor groups. Clinical data, including demographics, laboratory results, and 28-day outcomes, were collected.ResultsThe incidence rate of CRS1 in AMI patients was 15.2% (274 in 1801). Ultimately, 88 patients were enrolled and 25 (28.4%) were classified into the deceased group, while 63 were classified into the survivor group. There were statistically significant differences between the groups for hypertension, mechanical ventilation, KIDGO stage, NT-proBNP, Hb, ALB, PCI, decreased LVEF, 7th-day SCr value, and the highest SCr value recorded within 7 days (all P < 0.05). Multivariate logistic regression showed that the following factors were significantly related to whether a patient died: requiring mechanical ventilation, increased NT-proBNP levels and 7th-day SCr values, and decreased LVEFs. The APACHE II, SOFA, and SASP II scores on the 7th day were significantly higher in the deceased group (all P < 0.05). The accuracy of APACHE II, SOFA, and SASP II scores on the 7th day for predicting death were 84.1%, 78.4% and 79.5%, respectively. The AUC of 7th-day APACHE II, SOFA, and SASP II scores was 0.844, 0.803, and 0.827, respectively, with no statistically significant differences between the three scores (P > 0.05).ConclusionThe mortality rate of CRS1 in AMI patients was 28.4% (25 in 88) within 28 days. Mechanical ventilation, increased NT-proBNP levels, the 7th-day SCr value, and decreased LVEF were related to death in AMI patients with CRS1. APACHE II, SOFA, and SAPS II scores on the 7th day were satisfactorily accurate in predicting death within 28 days.

Diabetes modulation of the myocardial infarction-acute kidney injury axis.

As there is cross talk in functions of the heart and kidney, acute or chronic injury in one of the two organs provokes adaptive and/or maladaptive responses in both organs, leading to cardiorenal syndrome (CRS). Acute kidney injury (AKI) induced by acute heart failure is referred to as type 1 CRS, and a frequent cause of this type of CRS is acute myocardial infarction (AMI). Diabetes mellitus increases the risk of AMI and also the risk of AKI of various causes. However, there have been only a few studies in which animal models of diabetes were used to examine how diabetes modulates AMI-induced AKI. In this review, we summarize findings regarding the mechanisms of type 1 CRS and the impact of diabetes on both AMI and renal susceptibility to AKI and we discuss mechanisms by which diabetes modulates AMI-induced AKI. Hemodynamic alterations induced by AMI could be augmented by diabetes via its detrimental effect on infarct size and contractile function of the noninfarcted region in the heart. Diabetes increases susceptibility of renal cells to hypoxia and oxidative stress by modulation of signaling pathways that regulate cell survival and autophagy. Recent studies have shown that diabetes mellitus even at early stage of cardiomyopathy/nephropathy predisposes the kidney to AMI-induced AKI, in which activation of Toll-like receptors and reactive oxygen species derived from NADPH oxidases are involved. Further analysis of cross talk between diabetic cardiomyopathy and diabetic kidney disease is necessary for obtaining a more comprehensive understanding of modulation of the AMI-AKI axis by diabetes.

Identification and Validation of Pathogenic Genes in Sepsis and Associated Diseases by Integrated Bioinformatics Approach.

Sepsis is a clinical syndrome with high mortality and morbidity rates. In sepsis, the abrupt release of cytokines by the innate immune system may cause multiorgan failure, leading to septic shock and associated complications. In the presence of a number of systemic disorders, such as sepsis, infections, diabetes, and systemic lupus erythematosus (SLE), cardiorenal syndrome (CRS) type 5 is defined by concomitant cardiac and renal dysfunctions Thus, our study suggests that certain mRNAs and unexplored pathways may pave a way to unravel critical therapeutic targets in three debilitating and interrelated illnesses, namely, sepsis, SLE, and CRS. Sepsis, SLE, and CRS are closely interrelated complex diseases likely sharing an overlapping pathogenesis caused by erroneous gene network activities. We sought to identify the shared gene networks and the key genes for sepsis, SLE, and CRS by completing an integrative analysis. Initially, 868 DEGs were identified in 16 GSE datasets. Based on degree centrality, 27 hub genes were revealed. The gProfiler webtool was used to perform functional annotations and enriched molecular pathway analyses. Finally, core hub genes (EGR1, MMP9, and CD44) were validated using RT-PCR analysis. Our comprehensive multiplex network approach to hub gene discovery is effective, as evidenced by the findings. This work provides a novel research path for a new research direction in multi-omics biological data analysis.

Venous impedance index and its relation with renal outcomes in patients with heart failure and renal dysfunction

Background. The prevalence of chronic kidney disease (CKD) is increasing every year, which increases the risk of cardiovascular disease and even death. In Cardiorenal syndrome type 2 (CRS2), chronic cardiac dysfunction causes renal dysfunction. The aim of this study was to evaluate Doppler ultrasound of renal veins, calculate venous impedance index (VII) and determine their associations with the prognosis of CRS2 syndrome in patients with a history of chronic heart disease and CKD with a good forward function. Methods. In this descriptive-analytical study, 49 patients referred to Imam Reza Hospital in Tabriz with heart failure and renal dysfunction were selected. Renal status, VII and ejection fraction (EF) were evaluated. Results. Mean age of the patients was 61.83±12.39 years, 42.9% of which were women and 57.1% were men. The durations of heart and renal failure were 33.16 ± 13.8 and 11.76±5.1 months, respectively. Significant associations were found between VII and EF of the right and left kidneys (P=0.01 and P =0.03, respectively). But there was no statistically significant relationship between renal function and EF (P =0.54). With increasing edema rate, both VII and EF were decreased; however, these associations were not statistically significant (P &gt;0.05). Conclusion. According to the results, significant associations were found between VII and EF of right and left kidneys, however, no statistically significant correlations were observed between edema and VII mean and EF.

Experimental Cardiorenal Syndrome Type 3: What Is Known so Far?

BackgroundThe concept of cardiorenal syndrome (CRS) has been established more than 10 years ago. Five distinct types of CRS have been defined. In CRS type 3, acute kidney injury (AKI) induces cardiac complications such as ventricular decompensation due to arrhythmias, myocardial ischemia, or fluid retention with or without arterial hypertension. The risk of cardiovascular events in AKI has been known for many years, even long before the introduction of the CRS concept. However, epidemiological and clinical studies published in recent years increasingly emphasized CRS type 3 (and the remaining four types also) as separate entity which requires particular therapeutic attention in an interdisciplinary manner. However, only a limited number of experimental studies specifically addressed CRS type 3 so far. Our review aims to summarize experimental studies on the pathological mechanisms in CRS type 3.MethodsThe following search criteria were employed in order to identify articles published on the topic: “cardiorenal syndrome 3” OR “cardiorenal syndrome type 3” OR “CRS type 3” OR “CRS 3” AND “experimental” OR “mouse” OR “mice” OR “rats” OR “animals”; additional criteria were “myocardium” AND “ischemia” AND “kidney” OR “renal”. By applying the search criteria mentioned earlier, 10 references were finally selected.ResultsBy applying the search strategy, 10 experimental studies were finally selected. All included cardiac outcome analysis in AKI animals. The data clearly provide evidence for cardiac complications that evolve independently from excretory kidney dysfunction. Pathological processes that emerge in the heart of animals subjected to renal ischemia involve inflammation, a dysbalance of redox components, pro-apoptotic processes, and mitochondrial dysfunction.ConclusionThe findings may explain why AKI increases the risk of acute cardiac complications even if dialysis treatment has been initiated.

The Impact of Cardio Renal Syndrome (CRS) in Renal Transplant Recipients: A Systematic Review

Cardiovascular disease is a major cause of morbidity and mortality in patients with CKD. This risk is increased fivefold in renal transplant patients when compared to an age-matched population. This study aims to explore and focus on the risk factors, management, and outcomes of cardiorenal syndrome in renal transplant recipients and to estimate its deleterious effect on the heart and renal allograft, opening the door for future randomized clinical trials to look at the problem in more depth. The current literature has little information and data on the impact of cardiorenal syndrome on the renal allograft and heart regardless of the specific type of cardiorenal syndrome. Renal transplant recipients can develop any one of the five types of the cardiorenal syndrome because of having both conventional and established risk factors for developing CRS. These risk factors particularly the established ones or best described as non-traditional risk factors such as immunosuppressive medications, acute renal allograft rejection, suboptimal renal allograft function, anemia, infections, proteinuria, and hyperparathyroidism are usually neglected after renal transplantation. Although the prevalence of CRS is low among renal transplant recipients, we believe that is due to under diagnosis and lack of clinical trials leading to a knowledge gap in this subject area. Methodology: The present study conducted a systematic literature review and selected four Clinical trials of CRS in renal transplant recipients for datasets analysis to gain more knowledge about the risk factors contributing to CRS in renal transplant recipients and to produce a strategy to prevent CRS and manage such patients better. Results: This systematic review of the current literature revealed that the presence of non-traditional risk factors post-renal transplantation when combined with traditional risk factors can significantly increase the risk of developing CRS where the prognosis is almost always poor in such patients. The study also showed no difference in the preventive measures and management of CRS between renal transplant recipients and non-renal transplant recipients. Conclusion: Renal transplant recipients are at increased risk of developing CRS with poor outcomes compared to non-renal transplant recipients because of the additional non-traditional risk factors post-renal transplantation. However, the preventive measures and management of CRS in renal transplant recipients are similar to those used for the general population but more attention should be paid to the correction of non-traditional risk factors.

Value of Combined Plasma NGAL, Cystatin C and NT-proBNP in the Diagnosis of Cardiorenal Syndrome Type 1

Background: The presence of acute kidney injury in the setting of acute heart failure (AHF) or acute decompensated heart failure (ADHF) is very common occurrence and was termed cardiorenal syndrome 1 (CRS1). Neutrophil gelatinase-associated lipocalin (NGAL) in the blood and urine is one of the earliest biomarkers of acute kidney injury due to ischemia or renal toxicity. Cystatin C is early marker of renal dysfunction. NT-pro BNP is valuable in the diagnosis, prognosis and treatment of acute and chronic heart failure. This study was aimed to evaluate the diagnostic efficacy of the combination of plasma NGAL, Cystatin C and NTproBNP in diagnosis of CRS1. Methods: there were 139 patients with AHF or ADHF in the department of Cardiovascular resuscitation and Interventional cardiology at Ho Chi Minh City 115People Hospital from November 2018 to May 2019. This was a prospective cohort study. Results: there were 48 cases (rate 34.5%) with CRS1, mean age 66.12 ± 15.77, men accounted for 50.4%. There were no significant differences of vital signs on admission, diagnosis, type of heart failure between CRS1 and Non-CRS1 groups. The urea, creatinin on first day (creatininD1) and third day (creatininD3), NT-pro BNP, Cystatin C, NGAL levels were higher in the group with CRS1 than Non-CRS1, the difference was statistically significant p 353.23 ng/ml, Area Under Curve (AUC)was 0.732 (95% CI 0.65-0.80, p 1.81 mg/dl, AUC was 0.787 (95% CI 0.71-0.85, p &lt; 0.001), sensitivity 53.19%, specificity 77.17%, positive predictive value 54.3%, negative predictive value 76.3%.Combined three biomarker plasma NGAL, Cystatin C and NT proBNP, the specificity of the diagnosis was the highest 95.6%, the positive predictive value was the highest 84.62% in diagnosing CRS1. Conclusions: The combined plasma NGAL, Cystatin C and NT-pro BNP is high value in the diagnosis of CRS1 in patients with AHF or ADHF.

Eplerenone Prevents Cardiac Fibrosis by Inhibiting Angiogenesis in Unilateral Urinary Obstruction Rats.

Introduction Cardiovascular disease constitutes the leading cause of mortality in patients with chronic kidney disease (CKD), which is termed cardiorenal syndrome type 4 (CRS-4). Here, we report the development of pathological cardiac remodeling and fibrosis in unilateral urinary obstruction (UUO) rats. Methods Hematoxylin and eosin (H&E) staining was performed to observe the pathology of myocardial tissue. The degree of myocardial tissue fibrosis was observed by Masson and Sirius red staining. Immunohistochemical staining was applied to detect the expression of CD34 and CD105 in myocardial tissue, and immunofluorescent staining was performed to examine the expression of CD34, collagen I/collagen III, and alpha smooth muscle actin (α-SMA). The expression of the signal pathway-related proteins vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2), nuclear factor κB (NF-κB), and interleukin (IL)-1β was tested by western blotting. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the mRNA levels of serum and glucocorticoid-inducible kinase (SGK)-1, NF-κB, and interleukin-1β (IL-1β). Results The results showed the development of pathological cardiac remodeling and cardiac dysfunction in UUO rats. Moreover, there was more angiogenesis and endothelial-mesenchymal transition (End-MT) in the UUO group, and these effects were inhibited by eplerenone. Conclusions The results indicated that this cardiac fibrosis was associated with angiogenesis and that End-MT was related to aldosterone and mineralocorticoid receptor (MR) activation. Moreover, in association with the MR/IL-1β/VEGFA signaling pathway, early treatment with the MR antagonist eplerenone in rats with UUO-induced CKD may significantly attenuate MR activation and cardiac fibrosis.

BI-1 ameliorates myocardial injury by activating the mitochondrial unfolded protein response and FUNDC1-related mitophagy in cardiorenal syndrome type 3

It has been suggested that mitochondrial dysfunction underlies the myocardial injury seen following cardiorenal syndrome type 3 (CRS-3). Both mitophagy and the mitochondrial unfolded protein response (UPRmt) are protective programs that preserve mitochondrial homeostasis. Here, we explored whether Bax inhibitor-1 (BI-1) overexpression attenuates CRS-3-related myocardial injury through activation of mitophagy and the UPRmt in cardiomyocytes. Following CRS-3 induction via renal ischemia-reperfusion injury, BI-1 transgenic (BI1TG) mice showed greater preservation of myocardial integrity and relaxation function and less cardiomyocyte apoptosis than wild-type (WT) mice. Moreover, BI-1 overexpression attenuated CRS-3-mediated myocardial inflammation, as indicated by decreased MCP-1 and IL-6 expression and normalized ATP production in cardiomyocytes. After CRS-3 induction, mitophagy was inhibited in cardiomyocytes from WT mice, as indicated by both decreased Fundc1 transcription and mt-Keima fluorescence, and modest activation of the UPRmt, denoted by a slight increase in Atf6 mRNA levels. By contrast, activation of mitophagy and marked UPRmt upregulation were observed in cardiac tissue from BI1TG mice. shRNA-mediated silencing of Fundc1 or Atf6 greatly impaired mitochondrial metabolism and survival in cultured cardiomyocytes overexpressing BI-1. Thus, upregulation of BI-1 expression aimed at activating mitophagy and the UPRmt may represent a useful therapeutic approach for the treatment of CRS-3.

N-terminal prohormone B-type natriuretic peptide variability acts as a predictor of poor prognosis in patients with cardiorenal syndrome type 2

ABSTRACT This study aims to explore the effect of N-terminal pro-brain natriuretic peptide (NT-proBNP) variability (mean absolute difference of the log2 NT-proBNP level measured in hospital) on the prognosis of patients with cardiorenal syndrome (CRS) type 2. Patients with CRS type 2 were retrospectively included. The varied NT-proBNP indications were analyzed. They were NT-proBNP I(pre-treatment), NT-proBNP II(post-treatment), NT-proBNP II/I, ΔNT-proBNP, log2 (NT-proBNP) variability and mean log2 (NT-proBNP). A logistic regression model and survival curves (Kaplan–Meier analysis) were built to identify independent predictors associated with poor prognosis. The primary outcomes were major adverse renal and cardiac events. The secondary outcome was all-cause mortality. From 2012 to 2016, 136 patients were included in this study with 69 (50.7%) had high log2 (NT-proBNP) variability level. The optimal cutoff level for each NT-proBNP indication that predicts poor prognosis was calculated, and the area under curves ranged from 0.668 to 0.891 with different indications. Kaplan–Meier analysis revealed that there was significantly correlated with prevalence of primary outcomes and NT-proBNP variability. The hazard ratios (HRs) ranged from 1.67 to 6.61 with different indications. The multivariate regression analyses also identified the risk of the primary outcomes were associated with elevated NT-proBNP values, except NT-proBNP I. The odds ratio (ORs) ranged from 1.83 to 6.61 with different indications. When analyzing the relationship between NT-proBNP variability and all-cause mortality, the results were the same. NT-proBNP variability might serve as an independent predictor for poor prognosis and all-cause mortality in patients with CRS type 2.

Extracellular Vesicles and Their Relationship with the Heart-Kidney Axis, Uremia and Peritoneal Dialysis.

Cardiorenal syndrome (CRS) is described as primary dysfunction in the heart culminating in renal injury or vice versa. CRS can be classified into five groups, and uremic toxin (UT) accumulation is observed in all types of CRS. Protein-bound uremic toxin (PBUT) accumulation is responsible for permanent damage to the renal tissue, and mainly occurs in CRS types 3 and 4, thus compromising renal function directly leading to a reduction in the glomerular filtration rate (GFR) and/or subsequent proteinuria. With this decrease in GFR, patients may need renal replacement therapy (RRT), such as peritoneal dialysis (PD). PD is a high-quality and home-based dialysis therapy for patients with end-stage renal disease (ESRD) and is based on the semi-permeable characteristics of the peritoneum. These patients are exposed to factors which may cause several modifications on the peritoneal membrane. The presence of UT may harm the peritoneum membrane, which in turn can lead to the formation of extracellular vesicles (EVs). EVs are released by almost all cell types and contain lipids, nucleic acids, metabolites, membrane proteins, and cytosolic components from their cell origin. Our research group previously demonstrated that the EVs can be related to endothelial dysfunction and are formed when UTs are in contact with the endothelial monolayer. In this scenario, this review explores the mechanisms of EV formation in CRS, uremia, the peritoneum, and as potential biomarkers in peritoneal dialysis.

Risk factors and outcome variables of cardiorenal syndrome type 1 from the nephrologist’s perspective

Background and aimIn cardiorenal syndrome (CRS) type 1, acute cardiac failure or acute decompensation of chronic heart failure causes acute kidney injury (AKI). Every individual AKI episode increases the risk for chronic kidney disease (CKD) in the long term. In this study, we aimed to evaluate epidemiological characteristics and outcome variables of CRS type 1 individuals from the nephrologist’s perspective.MethodsThe study was performed in a retrospective, observational manner. All AKI patients treated at the Brandenburg Hospital of the Medical School of Brandenburg between January and December 2019 were screened for diagnostic criteria of CRS type 1. Endpoints were in-hospital death, need for dialysis, and renal recovery.ResultsDuring the screening, 198 out of 1189 (16.6%) AKI subjects were assigned to the diagnosis CRS type 1. The overall in-hospital mortality was 19.2%; 9.6% of the patients required dialysis due to AKI. Complete recovery of kidney function was observed in 86 individuals (43.4%); incomplete recovery occurred in 55 patients (27.8%). Mortality-predictive variables were AKIN stage 2, longer ICU treatment, and insulin-dependent diabetes. Regarding dialysis, AKIN stage 3 and higher potassium at the time of diagnosis were predictive. Subjects with longer in-hospital stay recovered more often from CRS type 1.ConclusionsThe incidence of CRS type 1 is high (∼16% of all in-hospital AKI subjects) and the mortality is higher than the average mortality of AKI in general. At the same time, complete recovery of kidney function occurs less frequent. The kidney-related follow-up management of CRS type 1 needs to be significantly optimized to improve the long-term outcome of affected patients.

Value of combined Plasma NGAL, Cystatin C And NT-proBNP in the diagnosis of cardiorenal syndrome type 1

Abstract Background The presence of acute kidney injury in the setting of acute heart failure (AHF) or acute decompensated heart failure (ADHF) is very common occurrence and was termed cardiorenal syndrome 1 (CRS1). Neutrophil gelatinase-associated lipocalin (NGAL) in the blood and urine is one of the earliest biomarkers of acute kidney injury due to ischemia or renal toxicity. Cystatin C is early marker of renal dysfunction. NT-proBNP is valuable in the diagnosis, prognosis and treatment of acute and chronic heart failure. This study was aimed to evaluate the diagnostic efficacy of the combination of plasma NGAL, Cystatin C and NT-proBNP in diagnosis of CRS1. Methods There were 139 patients with AHF or ADHF in the department of Cardiovascular resuscitation and Interventional cardiology at Ho Chi Minh City 115 People Hospital from November 2018 to May 2019. This was a prospective cohort study. Results There were 48 cases (rate 34.5%) with CRS1, mean age 66.12±15.77, men accounted for 50.4%. There were no significant differences of vital signs on admission, diagnosis, type of heart failure between CRS1 and Non-CRS1 groups. The urea, creatinin on first day (creatininD1) and third day (creatininD3), NT-proBNP, Cystatin C, NGAL levels were higher in the group with CRS1 than Non-CRS1, the difference was statistically significant p&amp;lt;0.05. The optimal cut-off NGAL for diagnosing CRS1 was &amp;gt;353.23 ng/ml, Area Under Curve (AUC) was 0.732 (95% CI 0.65–0.80, p&amp;lt;0.001), sensitivity 74.47%, specificity 68.48%, positive predictive value 54.7%, negative predictive value 84%. The optimal cut-off Cystatin C for diagnosing CRS1 was &amp;gt;1.81 mg/dl, AUC was 0.787 (95% CI 0.71–0.85, p&amp;lt;0.001), sensitivity 75%, specificity 83.52%, positive predictive value 70.6%, negative predictive value 86.4%. The optimal cut-off NT-proBNP for diagnosing CRS1 was 17681 pg/ml, AUC was 0.683 (95% CI 0.59 – 0.76, p&amp;lt;0.001), sensitivity 53.19%, specificity 77.17%, positive predictive value 54.3%, negative predictive value 76.3%. Combined three biomarker plasma NGAL, Cystatin C and NTproBNP, the specificity of the diagnosis was the highest 95.6%, the positive predictive value was the highest 84.62% in diagnosing CRS1. Conclusions The combined plasma NGAL, Cystatin C and NT-proBNP is high value in the diagnosis of CRS1 in patients with AHF or ADHF. Funding Acknowledgement Type of funding sources: None.

The value of Cystatin C in the diagnosis of cardiorenal syndrome type 1

Abstract Background The presence of acute kidney injury in the setting of acute heart failure is very common occurrence and was termed cardiorenal syndrome 1 (CRS1). In CRS1 the diagnosis of acute kidney damage is often delayed by creatinine and urine output following KDIGO standards (Kidney Disease Improving Global Outcomes). Cystatin C is one of the earliest markers of worsening renal function. We studied the value of plasma Cystatin C in the diagnosis of cardiorenal syndrome type 1. Purpose This study was aimed: (1) to decribe clinical, subclinical characteristics, prevalence of CRS1; (2) to evaluate the diagnostic efficacy of Cystatin C in diagnosis of CRS1. Materials and method There were 139 patients with acute heart failure or acute decompensated heart failure (ADHF) in the Department of cardiovascular resuscitation and Interventional cardiology at 115 Ho Chi Minh City People's Hospital from September 2018 to June 2019. This is a prospective cohort study. Results There were 48 cases (rate 34.5%) with CRS1, medium age 66.12±15.77, men accounted for 50.4%. The optimal cut-off Cystatin C for diagnosing CRS1 is &amp;gt;1.81 mg/dl, AUC is 0.787 (95% CI 0.71–0.85, p&amp;lt;0.001), sensitivity 75%, specificity 83.52%, positive predictive value 70.6%, negative predictive value 86.4%. Building the optimal regression model by the BMA (Bayesian Model Average) method with only one variable Cystatin C: Odds Ratio = ey, while y = −2.75 + 1.11x Cystatin C. Moreover, a nomogram with variable Cystatin C was designed to predict the likelihood of CRS1 with AUC 0.842. Ultimately, a confusion matrix was constructed to determine model accuracy 81.82%, sensitivity 78.26%, specificity 100%, positive predictive value 100%, negative predictive value 47.37%. Conclusions Cystatin C is quite good value in the diagnosis of CRS1 in patients with acute heart failure or ADHF. A predictive model based on Cystatin C may help early diagnose CRS1 in patients with acute heart failure or ADHF. Funding Acknowledgement Type of funding sources: None.

Risk Factors and Outcome Variables of Cardiorenal Syndrome Type 1 from the Nephrological Perspective

Risk Factors and Outcome Variables of Cardiorenal Syndrome Type 1 from the Nephrological Perspective

IT'S NOT THE HEART

TOPIC: Pulmonary Vascular Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: HOHF is suspected when patients present with clinical symptoms of CHF but have an elevated CI typically above 4L/min/m2 [1]. These patients can exhibit signs and symptoms of CHF and have PH as a result of elevated blood flows through the pulmonary vasculature. CASE PRESENTATION: A 56 year-old male kidney transplant recipient (KTR) presented with shortness of breath, lower extremity edema 3-months after cadaveric renal transplantation. He had a history of chronic mild systolic cardiac dysfunction (EF 50%), pulmonary hypertension (WSPH group II), and diabetes mellitus type 2 prior to kidney transplantation. Physical exam was significant for +3 pitting edema of bilateral lower extremities, crackles at lung bases and a right brachiocephalic AVF with palpable thrill. Serum creatinine was 3.5mg/dL (baseline 2.0mg/dL) and Chest X ray showed pulmonary edema. Diuresis improved the edema and shortness of breath, but worsened renal function. Renal biopsy was negative for rejection. Echocardiography (TTE) revealed an elevated right ventricular systolic pressure (RVSP) and severely dilated right atrium (RA) and ventricle (RV). Right heart catheterization demonstrated elevated right and left sided filling pressures with moderate pulmonary hypertension (PH) and an elevated cardiac output/index (CO/CI). An AVF occlusion in the cath lab resulted in a significant reduction in CO 7.75 L/min and CI 3.10 L/min/m2 by thermodilution. Findings were consistent with PH secondary to high output heart failure (HOHF), likely related to AV fistula. He underwent an AVF revision with improvement of symptoms and renal function. DISCUSSION: PH is common in patients with ESRD undergoing HD via an AVF [2] and HOHF could be an easily addressable cause of PH in ESRD. HOHF can be difficult to diagnose based on echocardiography alone. RHC typically shows an elevated CO (> 8L/min, CI>4L/min/m2), AVF/G flow > 1.5L/min, and a cardiopulmonary recirculation ratio (CPR) > 0.3 [3]. Furthermore, PH prior to transplantation appears to have an adverse impact on allograft function in kidney transplant recipients (KTR) [4]. In a retrospective analysis of KTRs in a single institution, 29/113 (26%) of patients required closure of their AVF due to symptomatic CHF. The mean AVF flow rate was significantly elevated in patients requiring AVF closure compared to those managed conservatively (2197 ml/min vs. 851 ml/min) [5]. High flow rates due to increased arterial blood shunted from left to right circulation increased the preload and stroke volume and resulted in ventricular hypertrophy leading to subsequent heart failure [6]. CONCLUSIONS: In our patient, HOHF and PH secondary to an aneurysmal AVF resulted in acute cardio-renal syndrome type 1(CRS - 1) in the transplanted kidney. The improvement in both cardiac and renal function following the revision of AVF confirmed the diagnosis of cardiorenal injury due to an aneurysmal AVF. REFERENCE #1: Reddy YN, Obokata M, Dean PG, Melenovsky V, Nath KA, Borlaug BA. Long-term cardiovascular changes following creation of arteriovenous fistula in patients with end stage renal disease. Eur Heart J. 2017 Mar 6. REFERENCE #2: Schoenberg NC, Argula RG, Klings ES, Wilson KC, Farber HW. Prevalence and Mortality of Pulmonary Hypertension in ESRD: A Systematic Review and Meta-analysis. Lung. 2020 Jun;198(3):535-45. REFERENCE #3: Wijnen E, Keuter XH, Planken NR, van der Sande FM, Tordoir JH, Leunissen KM, et al. The relation between vascular access flow and different types of vascular access with systemic hemodynamics in hemodialysis patients. Artif Organs. 2005 Dec;29(12):960-4. DISCLOSURES: Advisory Committee Member relationship with Janssen pharmaceutical Please note: 4/2020 - 4/2021 Added 04/27/2021 by Rahul Argula, source=Web Response, value=Consulting fee Advisory Committee Member relationship with United Therapeutics Please note: 2019-2021 Added 04/27/2021 by Rahul Argula, source=Web Response, value=Consulting fee Advisory Committee Member relationship with Breathe Technologies Please note: 2019 Added 04/27/2021 by Rahul Argula, source=Web Response, value=Consulting feeeducational grant relationship with Reata pharmaceuticals Please note: 2018-2019 Added 04/27/2021 by Rahul Argula, source=Web Response, value=Grant/Research Consultant relationship with Accordant health / CVS Please note: 2020 - 2021 Added 04/27/2021 by Rahul Argula, source=Web Response, value=Consulting fee no disclosure on file for mona haj; No relevant relationships by Elena Vlachos, source=Web Response

Role of Megalin and Sex in AKI-CKD Transition due to Cardiorenal Syndrome Type 1

Role of Megalin and Sex in AKI-CKD Transition due to Cardiorenal Syndrome Type 1

Establishment of a Drug Screening Model for Cardiac Complications of Acute Renal Failure.

Acute renal failure (ARF) is a clinical critical syndrome with rapid and severe decline of renal function. Complications of ARF, especially its cardiac complications (cardiorenal syndrome type 3, CRS-3), are the main causes of death in patients with ARF. However, the shortage and limited efficacy of therapeutic drugs make it significant to establish new large-scale drug screening models. Based on the Nitroreductase/Metronidazole (NTR/MTZ) cell ablation system, we constructed a Tg(cdh17:Dendra2-NTR) transgenic zebrafish line, which can specifically ablate renal tubular epithelial cells. The absence of renal tubular epithelial cells can lead to ARF in zebrafish larvae. The ARF symptoms, such as heart enlargement, slow heart rate and blood stasis, are similar to the clinical manifestations of human CRS-3. Furthermore, two therapeutic drugs (digoxin and enalapril) commonly used in the clinical treatment of heart failure were also effective in alleviating the symptoms of CRS-3 in zebrafish, which proved the effectiveness of this model. Drug screening further discovered a potential drug candidate, α-lipoic acid, which can effectively alleviate the symptoms of CRS-3 through its antioxidant function. Accordingly, we established a new ARF model of zebrafish, which laid a foundation for large-scale screening of new therapeutic drugs for its complications.