Management Of Cardiorenal Syndrome Research Articles

Clinical practice guideline for the diagnosis and treatment of cardiorenal syndrome (2023 Edition)

The guideline was co-authored by a working group composed of multidisciplinary experts in nephrology, cardiology, critical care medicine, and evidence-based medicine. It focused on eight clinical issues concerning prediction, diagnosis and assessment of cardiorenal syndrome, prevention, treatment of drugs and their selection, mechanical circulatory support and blood purification therapy, heart and/or kidney transplantation, treatment of major complications, multidisciplinary combination therapy, and special diagnosis and treatment in children and pregnant women, mainly based on evidence-based evidence of cardiorenal syndrome, heart failure and chronic kidney disease. Meanwhile, the domestic and foreign clinical guidelines in related fields were referenced to put forward recommendations. The present guideline aims to guide and standardize the clinical practice of diagnosis, prevention, treatment and management of cardiorenal syndrome, promote the development of clinical trials, and improve the level of prevention, treatment and scientific research.

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.

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.

7 The Utility of POCUS Enhanced Physical Examination in the Management of Cardiorenal Syndrome

7 The Utility of POCUS Enhanced Physical Examination in the Management of Cardiorenal Syndrome

Acute Cardiorenal Syndrome: Epidemiology, Pathophysiology, Assessment, and Treatment

Acute cardiorenal syndrome (CRS) is often observed in patients with acute kidney injury (AKI) in the cardiac intensive care unit and is reported to be associated with poor prognosis. Volume disorder or re-distribution, renin-angiotensin-aldosterone system activation, and neurohormonal and sympathetic nervous system activation have been suggested to be related to the occurrence of acute CRS. There is a lack of biomarkers that can identify changes in renal function in patients with acute CRS. Evidence-based medications are limited in the management of acute CRS in AKI. Therefore, we reviewed the epidemiology, pathophysiology, clinical assessment, and treatment of acute CRS in AKI.

Protocolized Diuretic Strategy as a Treatment Algorithm for Cardiorenal Syndrome

Background: A diuretic strategy is needed that is superior to current clinical care in the management of cardiorenal syndrome. Current HF guidelines do not provide any standard protocol for diuretic dosing. Aim: To determine if a protocolized diuretic treatment strategy (ProDiuS), compared to usual care (UC), results in improved decongestion, clinical outcomes, and health-related quality of life (HRQOL), while preserving renal function in hospitalized patients with cardiorenal syndrome. Materials and Methods: This trial was a prospective randomized single-blind trial of participants hospitalized for cardiorenal syndrome from November 1, 2013 to July 9, 2015. Participants were randomized to ProDiuS vs. UC and followed daily in hospital, and at 1-month and 3-month follow-up. ProDiuS was a stepped diuretic strategy targeting daily urine output of 3-5 L/day. UC was care at the discretion of treating providers. The primary outcome, change in body weight (kg) from randomization to 96 hours (day 4), was compared between the ProDiuS and UC groups using the t-test. Data analysis for secondary outcomes between the two groups were conducted using the t-test or Wilcoxon rank sum test depending on whether data was skewed for continuous variables, as well as linear regression modeling. For ordinal variables or proportions, data were analyzed using the exact chi-square test and logistic regression modeling. For mortality, time to death was analyzed as time-to-event data, with censoring at the time of death, date of last follow-up, or the end of the study (3 month follow-up), using Kaplan-Meier curves and log-rank tests, and Cox proportional hazards models to adjust for continuous and discrete covariates in the survival analysis. Results: The study did not enroll the prespecified number of subjects due to slow recruitment. Out of 786 prescreened patients, 19 participants were included in the trial. There were no significant differences in baseline characteristics. Mean age was 68.7±7.3 years and 72.2% were male. There was borderline higher change in body weight from baseline to day 4 or discharge in ProDiuS vs. UC (-6.12 vs. -2.07 kg; p=0.05). Net negative fluid balance, length of hospitalization, HF rehospitalizations, mortality, acute kidney injury, adverse outcomes, and HRQOL scores were similar between groups. Conclusion: Due to small sample size, firm conclusions cannot be drawn. However, these findings suggest that ProDiuS results in similar clinical and HRQOL outcomes as UC in HF patients treated at a large tertiary medical center in the short term. This trial was conducted in an advanced HF population on specialized HF services, which may have attenuated the efficacy of ProDiuS vs. UC. Further studies with larger sample size and more diverse HF populations are needed to determine the efficacy and safety of ProDiuS. Several lessons learned in attempting to design a trial of protocolized diuretic strategy in the cardiorenal population are discussed.

Arteriovenous Fistulae in Chronic Kidney Disease and the Heart: Physiological, Histological, and Transcriptomic Characterization of a Novel Rat Model.

Background Arteriovenous fistulae (AVFs) are the gold standard for vascular access in those requiring hemodialysis but may put an extra hemodynamic stress on the cardiovascular system. The complex interactions between the heart, kidney, and AVFs remain incompletely understood. Methods and Results We characterized a novel rat model of five-sixths partial nephrectomy (NX) and AVFs. NX induced increases in urea, creatinine, and hippuric acid. The addition of an AVF (AVF+NX) further increased urea and a number of uremic toxins such as trimethylamine N-oxide and led to increases in cardiac index, left and right ventricular volumes, and right ventricular mass. Plasma levels of uremic toxins correlated well with ventricular morphology and function. Heart transcriptomes identified altered expression of 8 genes following NX and 894 genes following AVF+NX, whereas 290 and 1431 genes were altered in the kidney transcriptomes, respectively. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis revealed gene expression changes related to cell division and immune activation in both organs, suppression of ribosomes and transcriptional activity in the heart, and altered renin-angiotensin signaling as well as chronodisruption in the kidney. All except the latter were worsened in AVF+NX compared with NX. Conclusions Inflammation and organ dysfunction in chronic kidney disease are exacerbated following AVF creation. Furthermore, our study provides important information for the discovery of novel biomarkers and therapeutic targets in the management of cardiorenal syndrome.

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.

Influences of miR‐21* in the Heart–Kidney Axis

By influencing protein translation, microRNAs (miRNAs) have emerged as powerful regulators of a wide range of biological processes. In recent years, extraordinary progress has been made in terms of identifying the origin and exact functions of miRNAs. An important correlation has recently been made between the role of miRNAs and Cardiorenal Syndrome (CRS). A good candidate for investigating this has been determined to be dogs with Congestive Heart Failure (CHF) and those with CRS, using plasma samples. We intend to investigate the role of miRNAs in cell-to-cell communication by paracrine interactions resulting in these dysfunctions by analyzing levels of the passenger strand miR-21*. Animals and Procedures We collected blood samples from 9 healthy small breed client-owned dogs and 9 small breed client-owned dogs with CHF and CRS, ages 9 years and up. Blood samples were collected from affected dogs before administering medications for the management of CHF and CRS. Isolated microRNAs from plasma were obtained by processing the samples through the reverse transcription process, using Bio-Rad Lab's Reverse Transcription Kits. The resulting assays were then processed by the CFX Connect qPCR analysis machine, using the real-time quantitative PCR (polymerase chain reaction) process. This resulted in expression profiles of our samples. Discussion Exosome mediated communication has emerged as an important factor in interactions that lead to Cardiorenal Syndrome. The heart distributes nutrients and oxygen to other organs, including the kidney. The kidney is the major organ responsible for regulating salt and water balance. Impaired cardiac function leads to low cardiac output which lessens the efficiency of the kidney. This renal dysfunction then results in increased fluid retention, which impairs heart function further. miR-21 is highly expressed in the heart and kidneys and it has been shown that elevated levels of miR-21 lead to poor outcomes in most primary organ dysfunctions. Cardiac fibroblasts secrete miR-enriched exosomes, which are subsequently taken up by cardiomyocytes, in which they alter gene expression. In particular, a passenger strand miR, miR-21*, has been identified as a potent paracrine factor that induces cardiomyocyte hypertrophy when shuttled through exosomes.

Cardiorenal Syndrome in Type 2 Diabetes Mellitus - Rational Use of Sodium-glucose Cotransporter-2 Inhibitors.

Cardiorenal syndrome (CRS) in people with type 2 diabetes mellitus (T2DM) illustrates the bidirectional link between the heart and the kidneys, with acute or chronic dysfunction of one organ adversely impacting the function of the other. Of the five subtypes identified, type 1 and 2 CRS occur because of the adverse impact of cardiac conditions on the kidneys. Type 3 and 4 occur when renal conditions affect the heart, and in type 5, systemic conditions impact the heart and kidneys concurrently. The cardiovascular and renoprotective benefits evidenced with sodium-glucose cotransporter-2 (SGLT2) inhibitors make them a potential choice in the management of CRS. Cardiovascular protection is mediated by a reduction in cardiac workload, blood pressure, and body weight; with improvement in lipid profile, uric acid levels, and adaptive ketogenesis process. Renoprotection is facilitated by reduction in albuminuria and hypoxic stress, and restoration of tubuloglomerular feedback. The favourable effect on cardiovascular complications and death, as well as renal complications and progression to end-stage kidney disease, has been confirmed in clinical trials. Guidelines endorse first-line use of SGLT2 inhibitors after metformin in patients with T2DM with high cardiovascular risk, chronic kidney disease or both. Since most trials with SGLT2 inhibitors excluded subjects with acute illness, patients with CRS subtypes 1 and 3 have not been studied adequately, making SGLT2 initiation in clinical practice challenging. Ongoing trials may provide evidence for SGLT2 inhibitor use in CRS. This review aims to enhance understanding of CRS and provide guidance for judicious use of SGLT2 inhibitors in T2DM.

Cardio-nephrology MDT meetings play an important role in the management of cardiorenal syndrome.

Cardiorenal syndrome is a complex condition associated with significant morbidity in the form of symptoms secondary to fluid overload, leading to hospitalisations, and portends increased mortality. Both the diagnosis and management of the conditions are complicated by the fact that there is dysfunction of the heart as well as the kidney, usually with uncertainty with regards to the timing of the first insult. Management in primary care, or in the emergency setting, tends to be predominantly focused on short-term improvement in function of one organ, leading to deleterious effects on the other. A consensus multi-disciplinary approach involving both cardiologists and nephrologists has been advocated in order to devise a unified management plan. Our report presents findings of monthly cardio-nephrology multi-disciplinary team meetings and illustrates that this can be an efficacious approach both in terms of avoiding unnecessary outpatient clinic visits, as well as consensus decision-making.

Usefulness of Peritoneal Ultrafiltration in Patients with Diuretic Resistant Heart Failure without End-Stage Renal Disease

Aim: This study aimed to explore the role of peritoneal ultrafiltration (UF) in cardiorenal syndrome (CRS) patients for fluid and metabolic control. Background: Peritoneal UF is safely and efficiently used for the management of CRS. It has been shown to provide efficient UF in hypervolemic patients. Methods: Thirty (20 males and 10 females) CRS patients were treated by peritoneal dialysis (PD) and UF. The baseline data of the patients (demographics, causes of heart failure, the presence of pacemaker or implantable cardioverter-defibrillator, the need for extracorporeal UF or paracentesis or thoracentesis, comorbidity, drugs, left ventricular ejection fraction [LVEF] and pulmonary artery systolic pressure [PAPs], pericardial effusion, physical examination, body weight, NYHA class, dialysis regime, urine output, N-terminal pro-B-type natriuretic peptide [NT-proBNP] level, hemoglobin, estimated glomerular filtration rate [eGFR], and other routine biochemical determinations) were recorded at the onset, every 6 months, and then annually. Echocardiograms were performed at baseline and after 6 and 12 months. The time points of complications associated with PD, the need for hemodialysis, the day of death, and causes of death were documented. Results: Mean age was 69 ± 8 years (range 49–84 years). The average PD duration was 18.25 ± 14.87 months. According to the CKD-EPI, initial mean GFR was 34.34 ± 11.9 mL/min/1.73 m² (range 16.57–59.0), and this increased to 45.48 ± 26.04, 45.10 ± 28.58, and 41.10 ± 25.68 mL/min/1.73 m² in the third, sixth, and twelfth months, respectively. There was a significant increase in the first 3 months and a significant decrease between the third and twelfth months (respectively, p = 0.018 and p = 0.043). There was no difference in eGFR levels between baseline and the end of the first year (p = 0.217). In the first 3 months, there was a significant decline in urea levels to 79.38 ± 36.65 from 109.92 ± 42.44 mg/dL and this was maintained until the end of the first year of PD therapy (after 3 months, p = 0.002; after 1 year, p = 0.024). However, there was no significant change in creatinine levels within the first year (p = 0.312). There was a significant increase in hemoglobin level up to the end of the first year of PD (after 3 months, p = 0.000; after 12 months, p = 0.013). There was a marked decrease in NT-proBNP levels in the first 6 months (p = 0.011). Functional capacity (according to NYHA classification) improved in all patients by the third month of PD treatment (p < 0.001). This early improvement was maintained in many patients during the following 12 months (p < 0.001). There was a marked decrease in NT-proBNP levels in the first 6 months (p = 0.011). At the end of the first year, there was an approximate 15% reduction in NT-proBNP levels (p = 0.647). Hospitalizations decreased to 6 ± 15 days/patient-year (range 18–122 days) from 62 ± 24 days/patient-year (p = 0.000). Conclusion: Peritoneal UF is a treatment method that maintains renal function and electrolyte balance, improves cardiac function, and reduces hospitalizations in CRS patients. We observed that this treatment significantly increased functional capacity and quality of life and significantly reduced hospital admissions.

Acute Kidney Injury in Heart Failure Revisited-The Ameliorating Impact of "Decongestive Diuresis" on Renal Dysfunction in Type 1 Acute Cardiorenal Syndrome: Accelerated Rising Pro B Naturetic Peptide Is a Predictor of Good Renal Prognosis.

There is mounting evidence that forward heart failure as manifested by low cardiac output alone does not define the degree of renal dysfunction in cardiorenal syndrome. As a result, the term “congestive renal failure” was coined in 2012 by Ross to depict the role of renal venous hypertension in type 1 acute cardiorenal syndrome. If so, aggressive decongestive therapies, either through mechanical ultrafiltration with dialysis machines or pharmacologic ultrafiltration with potent diuretics, would lead to improved cardio and renal outcomes. Nevertheless, as recently as 2012, a review of this literature had concluded that a renal venous hypertension-directed approach using diuretics to manage cardio-renal syndrome was yet to be fully investigated. We, in this review, with three consecutive case series, describe our experience with pharmacologic decongestive diuresis in this paradigm of care and argue for studies of such therapeutic interventions in the management of cardiorenal syndrome. Finally, based on our observations in the Renal Unit, Mayo Clinic Health System, in Northwestern Wisconsin, we have hypothesized that patients with cardiorenal syndrome presenting with accelerated rising Pro B Naturetic Peptide levels appear to represent a group that would have good cardio- and renal-outcomes with such decongestive pharmacologic therapies.

Fluid overload as a major target in management of cardiorenal syndrome: Implications for the practice of peritoneal dialysis.

Congestion is an integral component of cardiorenal syndrome and portends an adverse impact on the outcomes. Recent studies suggest that congestion has the ability of modulating the interactions between the kidney and the heart in this setting. Peritoneal dialysis (PD) is a home-based therapeutic modality that is not only offered to patients with end-stage renal disease to provide solute clearance and ultrafiltration, but it has also been used in patients with refractory heart failure and fluid overload to help optimize volume status. Several uncontrolled studies and case series have so far evaluated the role of PD in management of hypervolemia for patients with heart failure. They have generally reported favorable results in this setting. However, the data on the outcomes of patients with end-stage renal disease and concomitant heart failure is mixed, and the proposed theoretical advantages of PD might not translate into improved clinical endpoints. Congestion is prevalent in this patient population and has a significant effect on their survival. As studies suggest that a significant subset of patients with end-stage renal disease who receive PD therapy are hypervolemic, suboptimal management of congestion could at least in part explain these conflicting results. PD is a highly flexible therapeutic modality and the choice of techniques, regimens, and solutions can affect its ability for optimization of fluid status. This article provides an overview of the currently available data on the role and clinical relevance of congestion in patients with cardiorenal syndrome and reviews potential options to enhance decongestion in these patients.

Vascular Dysfunction: A Key Player in Chronic Cardio-renal Syndrome.

This review summarizes the current methods for the functional assessment of vascular damage (e.g., assessment of endothelial function, measurement of pulse wave velocity, and pressure wave analysis) and describes the association between vascular dysfunction and chronic cardio-renal syndrome. Vascular dysfunction may contribute to the development and progression of heart failure. Additionally, vascular dysfunction, especially increased arterial stiffness and abnormal pressure wave reflection and central hemodynamics, has been reported to accelerate renal function decline. Furthermore, renal dysfunction worsens vascular pathophysiological abnormalities. Therefore, the functional assessment of vascular damage may be useful in the management of cardio-renal syndrome.

Current Approaches in Cardio-Renal Syndrome

In recent years, burden of cardiac and kidney diseases throughout the world is increasing. Studies show that the coexistence of both diseases contributes to increased mortality, morbidity, and healthcare costs. One of the major challenges facing health systems today is to prevent cardio-renal syndrome and provide quality health services to individuals with cardio-renal syndrome. The “cardio-renal syndrome” is a general term to describe different clinical conditions in which heart and kidney dysfunctions coexist. Although the incidence of cardio-renal syndrome is increasing, the evidences are limited about its pathophysiology and effective management. Severe problems may occur due to the interaction of neurohumoral, hemodynamic, and other less known factors in patients with cardio-renal syndrome. Therefore, the management of cardio-renal syndrome requires a multidisciplinary, mutifaceted and patient-centred approach. The most recent developments on the definition, classification, epidemiology, pathophysiology, and prevention and management strategies of cardio-renal syndrome are discussed in this revie.

Cardiorenal Syndrome

Cardiorenal syndromes (CRSs) with bidirectional heart-kidney signaling are increasingly being recognized for their association with increased morbidity and mortality. In acute CRS, recognition of the importance of worsening kidney function complicating management of acute decompensated heart failure has led to the examination of this specific outcome in the context of acute heart failure clinical trials. In particular, the role of fluid overload and venous congestion has focused interest in the most effective use of diuretic therapy to relieve symptoms of heart failure while at the same time preserving kidney function. Additionally, many novel vasoactive therapies have been studied in recent years with the hopes of augmenting cardiac function, improving symptoms and patient outcomes, while maintaining or improving kidney function. Similarly, recent advances in our understanding of the pathophysiology of chronic CRS have led to reanalysis of kidney outcomes in pivotal trials in chronic congestive heart failure, and newer trials are including changes in kidney function as well as kidney injury biomarkers as prospectively monitored and adjudicated outcomes. This paper provides an overview of some new developments in the pharmacologic management of acute and chronic CRS, examines several reports that illustrate a key management principle for each subtype, and discusses opportunities for future research.

Epidemiology, pathophysiology, clinical characteristics and management of childhood cardiorenal syndrome

Cardiorenal syndrome (CRS) is a new term recently introduced to describe the acute or chronic comorbid state of the heart and kidney that has been long known and frequently managed in very sick individuals. The tight and delicate coordination of physiological functions among organ systems in the human body makes dysfunction in one to lead to malfunction of one or more other organ systems. CRS is a universal very common morbidity in the critically ill, with a high mortality rate that has received very little research attention in children. Simultaneous management of heart and renal failures in CRS is quite challenging; the therapeutic choice made for one organ must not jeopardize the other. This paper reviews the epidemiology, pathophysiology, clinical characteristics and management of acute and chronic CRS in children.

Role of Biomarkers in the Diagnosis and Management of Cardio-Renal Syndromes

The complex interaction between heart and kidney disease has been increasingly recognized over the recent years. Pathologies within these two organs frequently coexist and, due to organ cross-talk, dysfunction in one often leads to problems in the other. The classification of the various forms of cardio-renal syndrome has made these interactions clearer. To aid in the diagnosis, management and prognosis of these conditions, many novel cardiac and renal biomarkers have emerged to supplement traditional markers which have limited specificity and sensitivity. In this review we will summarize the literature on novel renal behind these and other biomarkers and discuss their potential relevance to the clinical scenarios of cardio-renal syndrome.

Effects of Statins on Cardiorenal Syndrome

Cardiovascular disease and renal disease have a close relationship that forms a vicious cycle as a cardiorenal syndrome (CRS). Oxidative stress, endothelial dysfunction, and vascular inflammation could be therapeutic targets when the renin-angiotensin-aldosterone system is activated by accumulation of conventional cardiovascular risk factors; however, a strategy for management of CRS has not been established yet. Statins, HMG-CoA reductase inhibitors, have not only cholesterol-lowering effects but also pleiotropic effects on cardiovascular systems, including anti-inflammatory and antioxidant effects and improvement of nitric oxide bioavailability. Since recent studies have indicated that statins have beneficial effects on chronic kidney disease and heart failure as well as coronary artery disease in cholesterol-lowering-dependent/independent manners, treatment with statins might be a successful strategy for preventing deterioration of CRS.