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A man in his eighties with acute heart failure and cardiorenal syndrome developed severe hypernatraemia with diuresis. In this situation, palliation is often considered when renal replacement therapy is inappropriate. The literature to guide treatment of dysnatraemia in this setting is limited. Diuretics often worsen hypernatraemia and fluid replacement exacerbates heart failure. We describe a successful approach to this clinical Catch-22: sequential nephron blockade with intravenous 5% dextrose. Seemingly counterintuitive, the natriuretic effect of this combination had not previously been compared with diuretic monotherapy for heart failure. Yet this immediately effective strategy generated a high natriuresis-to-diuresis ratio and functioned as a bridge to cardiac resynchronisation therapy (CRT). In conjunction with a low salt diet, CRT facilitated the maintenance of sodium homeostasis and fluid balance. Thus, by improving the underlying pathophysiology (ie, inadequate cardiac output), CRT may enhance the outcomes of patients with cardiorenal syndrome and hypernatraemia.

Background: Chronic kidney disease (CKD) has been associated with adverse clinical outcomes. Hyponatremia, a marker of illness severity and poor prognosis, is commonly exhibited in patients with CKD. Methods: This cross-sectional study included patients hospitalized due to heart failure (HF). We used stepwise logistic regression to investigate the independent association of cardiovascular drugs, markers of HF severity, and baseline clinical characteristics with hyponatremia in three subgroups ; normal renal function, mild-to-moderate CKD, and severe CKD. Results: Of the 1232 patients, 38.6% were hyponatremic. Patients with severe CKD, compared to those with normal renal function and mild-to- moderate CKD, were more likely to be hyponatremic (47.1%, 34.4% and 36.6%, respectively ; p

Sodium-glucose cotransporter-2 inhibitors were approved as adjunct therapy for the management of type 2 diabetes and have become a high-level recommendation for this population with cardiorenal metabolic syndrome. In addition, evidence continues to grow supporting this class of medications for people with heart failure and chronic kidney disease, regardless of diabetes status. This narrative review summarizes the sodium-glucose cotransporter inhibitors for cardiorenal metabolic syndrome.

Background Cardiorenal syndromes (CRSs) are reputed to result in worse prognosis than isolated heart failure (HF) and chronic kidney disease (CKD). Whether it is true for all major outcomes over the long-term regardless of CRS chronology (simultaneous, cardiorenal and renocardiac CRS) is unknown. Methods The 5-year adjusted risk of major outcomes was assessed in this nationwide retrospective cohort study in all 385 687 with either CKD or HF (out of 5 123 193 patients who were admitted in a French hospital in 2012). Results Overall, 84.0% patients had HF and 8.9% had CKD (they had similar age, sex ratio, diabetes and hypertension prevalence), while 7.1% had CRS (cardiorenal: 44.6%, renocardiac: 14.5%, simultaneous CRS: 40.8%). The incidence of major outcomes was 57.3%, 53.0%, 79.2% for death; 18.8%, 10.9%, 27.5% for cardiovascular death; 52.6%, 34.7%, 64.3% for HF; 6.2%, 5.5%, 5.6% for myocardial infarction (MI); 6.1%, 5.8%, 5.3% for ischaemic stroke; and 23.1%, 4.8%, 16.1% for end-stage kidney disease (ESKD) for isolated CKD, isolated HF and CRS, respectively. As compared with isolated CKD or HF, the risk of death, cardiovascular death and HF was markedly increased in CRS, the worse phenotype being cardiorenal CRS, while the increased risk of MI and ischaemic stroke associated with CRS subtypes was statistically but not clinically significant. As compared with isolated CKD, the risk of ESKD was similar for cardiorenal CRS only and marginally increased for renocardiac and simultaneous CRS. We could not find a synergy between HF and CKD on major clinical outcomes in the whole population (n = 5 123 193 patients). Conclusions The additional impact of CRS versus isolated HF or CKD on long-term kidney and cardiovascular risk is highly heterogenous, depending of the event considered and CRS chronology. No synergy between HF and CKD could be demonstrated.

Background Left ventricular hypertrophy and heart failure with preserved ejection fraction (HFpEF) are primary manifestations of the cardiorenal syndrome in patients with chronic kidney disease (CKD). Therapies that improve morbidity and mortality in HFpEF are lacking. Cell-based therapies promote cardiac repair in ischemic and non-ischemic cardiomyopathies. We hypothesized that cell-based therapy ameliorates CKD-induced HFpEF. Methods and Results Yorkshire pigs (n = 26) underwent 5/6 embolization-mediated nephrectomy. CKD was confirmed by increased creatinine and decreased glomerular filtration rate (GFR). Mean arterial pressure (MAP) was not different between groups from baseline to 4 weeks. HFpEF was evident at 4 weeks by increased LV mass, relative wall thickening, end-diastolic pressure, and end-diastolic pressure-volume relationship, with no change in ejection fraction (EF). Four weeks post-embolization, allogeneic (allo) bone marrow-derived mesenchymal stem cells (MSC; 1 × 107 cells), allo-kidney-derived stem cells (KSC; 1 × 107 cells), allo-cell combination therapy (ACCT; MSC + KSC; 1:1 ratio; total = 1 × 107 cells), or placebo (Plasma-Lyte) was delivered via intra-renal artery. Eight weeks post-treatment, there was a significant increase in MAP in the placebo group (21.89 ± 6.05 mmHg) compared to the ACCT group. GFR significantly improved in the ACCT group. EF, relative wall thickness, and LV mass did not differ between groups at 12 weeks. EDPVR improved in the ACCT group, indicating decreased ventricular stiffness. Conclusions Intra-renal artery allogeneic cell therapy was safe in a CKD swine model manifesting the characteristics of HFpEF. The beneficial effect on renal function and ventricular compliance in the ACCT group supports further research of cell therapy for cardiorenal syndrome.

Background: Congestive heart failure (CHF) associated with worsening renal function is a very common disorder, and, as well known, the goal of the treatment is reducing venous congestion and maintaining a targeted extracellular volume. The objective of the study is to evaluate regular peritoneal ultrafiltration treatment compared to a standard conservative approach in NYHA III–IV CHF patients. In particular, the primary endpoints of the study were the major event-free survival and the total days of medical care per month (which consist of the days of hospitalization and the number of outpatient visits). Material and Methods: This is a retrospective case-control study. Twenty-four patients were included in the present study. Twelve consecutive patients were treated with peritoneal treatment (group A) and 12 matched for age, gender, and severity of disease with a standard approach. Patients were observed over a maximum period of 18 months. Information on events, hospitalizations, and number of visits was collected during follow-up. Results: During the follow-up, we observed a major event in 4 patients in group A (33.3%) and in 8 patients in group B (66.7%). In group B, we observed 7 deaths and 1 ICD shock, while in group A, 3 deaths and 1 ICD shock. The number of visits per month was significantly lower in patients treated with the peritoneal method (1.2 [0.4–4.1] vs. 2.5 [2.0–3.1]; p = 0.03). The total days of medical care was significantly lower in group A (2.0 [1.1–5.5] vs. 4.4 [3.0–8.7]; p = 0.034). A multiple event analysis according to the Andersen-Gill model showed a significant event-free survival for group A. During the follow-up, we did not observe any episode of peritonitis in the treated group. Conclusions: Our study shows that the peritoneal technique is a good therapeutic tool in well-selected patients with CHF. In accordance with prior experience, this intervention has not only an important and significant clinical impact but also potential economic and social consequences.

Cardiorenal syndrome I (CRS-1) denotes a state in which acute kidney injury occurs in the setting of acute heart failure (AHF). Isoproterenol (Iso) administration is widly used as an AHF model by transiently inducing extreme tachycardia, hypotension, and myocyte apoptosis and/or necrosis. To gain potential insights into renal manifestations of CRS-1, mice were subjected to the Iso-AHF model (50 mg Iso/kg), followed by renal functional and renal cortical assessments over 4 hours Iso induced acute azotemia (doubling of BUN, plasma creatinine) and significantly reduced renal plasma flow (prolonged plasma para-amino-hippurate clearance). Although no morphologic tubular injury was identified, marked increases in renal cortical 'stress markers' (NGAL, HO-1, IL-6, MCP-1 mRNAs) and oxidant stress (decreased glutathione, increased malondialdehyde) were observed. These changes were catalytic Fe dependent, given that the iron chelator desferrioxamine (DFO) significantly blunted, or completely reversed, these renal cortical abnormalities. Despite these acute changes, no lasting renal injury was observed (assessed over 3 days). To determine whether Iso directly impacts tubular cell integrity, cultured proximal tubule (HK-2) cells were exposed to Iso. Substantial Fe dependent cell injury (decreased MTT uptake), and Fe independent increases in HO-1/IL-6 mRNA expression were observed. We conclude that Iso-induced AHF is a useful reversible model of CRS-1. Despite its largely hemodynamic ('pre-renal') nature, Fe-mediated oxidative stress and pro-inflammatory reactions are induced. These arise, at least in part, from direct Iso- induced tubular cell toxicity, rather than simply being secondary to Iso-mediated hemodynamic events. Finally, Iso-triggered renal cytokine production can potentially contribute to 'organ cross talk' and a systemic pro-inflammatory state.

Heart failure and renal insufficiency as well as pulmonary hypertension are pathophysiologically closely associated as a cardio-renal or cardio-pulmonary-renal syndrome. Due to the frequent hospitalization of patients affected by this syndrome, it is of high medical and also health economic relevance. Besides the inhibition of the renin-angiotensin-aldosterone system (RAAS), multimodal treatment options are available with mineralocorticoid receptor antagonists, angiotensin receptor-neprilysin inhibitors and sodium-glucose transporter 2 (SGLT-2) inhibitors. Profound knowledge of the pathophysiology and the therapeutic options is as necessary for an optimized medical care as patient-oriented, transdisciplinary and cross-sectoral care.

Background Malnutrition is frequent in patients with heart failure (HF) and contributes to increased systemic congestion, but also hinders its correct assessment, especially during decompensations. Estimating the degree of malnutrition and its relationship with systemic congestion is important to optimize treatment during decompensations. Material and methods Retrospective cohort study in patients with acute HF. The population was stratified according to CONUT (Controlling Nutritional Status) and PNI (Prognostic Nutritional Index) nutrition indices in order to analyse their relationship with objective parameters of congestion and the prognostic value of malnutrition. Results 309 patients were included. More than half presented some degree of malnutrition upon admission. The degree of congestion was significantly higher in malnourished patients, with a higher proportion of «comet tail artifacts» and a higher relative plasma volume. NT-proBNP concentrations, both on admission and at discharge, were also significantly higher in malnourished patients, regardless of the scale used. The univariate analysis identified the CONUT and PNI index as factors associated with one-year mortality from any cause (HR 1.62 [1.22–2.14]; p = 0.001) and PNI (HR 65 [0.53–0.80]; p ≤ 0.001), respectively. Conclusions A higher degree of malnutrition (determined by means of the CONUT and PNI indices) in patients with acute HF was associated with a higher presence of objective parameters of congestion and a higher one-year all-cause mortality.

Markers used in everyday clinical practice cannot distinguish between the permanent impairment of renal function. Sodium and potassium values and their interdependence are key parameters in addition to volemia for the assessment of cardiorenal balance. The aim of this study was to investigate volemia and electrolyte status from a clinical cardiorenal viewpoint under consideration of renal function utilizing artificial intelligence. In this paper, an analysis of five variables: B-type natriuretic peptide, sodium, potassium, ejection fraction, EPI creatinine-cystatin C, was performed using an algorithm based on the adaptive neuro fuzzy inference system. B-type natriuretic peptide had the greatest influence on the ejection fraction. It has been shown that values of both Na+ and K+ lead to deterioration of the condition and vital endangerment of patients. To identify the risk of occurrence, the model identifies a prognostic biomarker by random regression from the total data set. The predictions obtained from this model can help optimize preventative strategies and intensive monitoring for patients identified as at risk for electrolyte disturbance and hypervolemia. This approach may be superior to the traditional diagnostic approach due to its contribution to more accurate and rapid diagnostic interpretation and better planning of further patient treatment

A substantial proportion of patients with heart failure (HF) receive suboptimal guideline-recommended therapy. We aimed to identify the factors leading to suboptimal drug prescription in HF and according to HF phenotypes. This retrospective, single-centre observational cohort study included 702 patients admitted for worsening HF (HF with a reduced ejection fraction [HFrEF], n = 198; HF with a mildly reduced EF [HFmrEF], n = 122; and HF with a preserved EF [HFpEF], n = 382). A score based on the prescription and dose percentage of ACEi/ARBs, β-blockers, and MRAs at discharge was calculated (a total score ranging from zero to six). Approximately 70% of patients received ACEi/ARBs/ARNi, 80% of patients received β-blockers, and 20% received MRAs. The mean HF drug dose was approximately 50% of the recommended dose, irrespective of the HF phenotype. Ischaemic heart disease was associated with a higher prescription score (ranging from 0.4 to 1) compared to no history of ischaemic heart disease, irrespective of the left ventricular EF (LVEF) level. A lower prescription score was associated with older age and male sex in HFrEF and diabetes in HFmrEF. The overall ability of the models to predict the optimal drug dose, including key HF variables (including natriuretic peptides at admission), was poor (R2 < 0.25). A higher prescription score was associated with a lower risk of re-hospitalization and death (HR: 0.75 (0.57–0.97), p = 0.03), irrespective of phenotype (p-interaction = 0.41). Despite very different HF management guidelines according to LVEF, the prescription pattern of HF drugs is poorly related to LVEF and clinical characteristics, thus suggesting that physician-driven factors may be involved in the setting of therapeutic inertia. It may also be related to drug intolerance or clinical stability that is not predicted by the patients’ profiles.

Cardiorenal syndromes (CRS) describe disorders effecting critically ill and hospitalized patients with concurrent heart and kidney dysfunction. The presence of CRS is associated with a poor prognosis. This article is a review of the epidemiology, pathology, and evidence-based evaluation and management strategies for cardiorenal syndromes. All nurses should understand the significance that chronic heart and kidney disease has upon a patient's risk for CRS. Registered and advanced practice nurses should maintain the knowledge and skills of understanding the pathology of CRS to improve the evaluation and management of patients who present with CRS.

Cardio-renal syndrome is a challenging clinical entity to manage, and is often associated with increased morbidity and mortality. We hypothesized that adaptive servo-ventilation (ASV), non-invasive positive pressure ventilation that ameliorates systemic/pulmonary congestion, may improve renal function in patients with symptomatic heart failure complicated by the cardio-renal syndrome. Patients with symptomatic congestive heart failure who underwent ASV therapy for over 1 month were included in this retrospective study. The trajectory of the estimated glomerular filtration ratio (eGFR) between the pre-1 month period and the post-one-month period (on ASV) were compared. A total of 81 patients (median 65 years old, 65 men) were included. eGFR decreased during the pre-1 month period from 52.7 (41.7, 64.6) down to 49.9 (37.3, 63.5) mL/minute/1.73 m2 (P < 0.001) whereas we observed an increase following one-month of ASV therapy up to 53.4 (38.6, 68.6) mL/minute/1.73 m2 (P = 0.022). A reduction in furosemide equivalent dose following the initiation of ASV therapy was independently associated with increases in eGFR with an adjusted odds ratio of 13.72 (95% confidence interval 3.40-55.3, P < 0.001). In conclusion, short-term ASV therapy was associated with the preservation of renal function, particularly when the dose of loop diuretics was concomitantly reduced.

Coronary heart disease (CHD) has become the primary cause of death worldwide in both developed and developing countries.1 In China, the mortality rates of CHD in urban and rural residents were 122.04/100,000 and 115.32/100,000, respectively, in 2017.2 The Global Burden of Disease study reported that ischemic heart disease led to approximately 1.7 million deaths in China in 2016.3 CHD has become the leading cause of death in the Chinese population and a serious public health problem. In particular, acute coronary syndrome (ACS) is the chief and serious type of CHD, leading to ventricular remodeling and heart failure.4 Previous studies have also found that patients with ACS have a higher incidence of renal dysfunction.5,6 In recent years, the concept of cardiorenal syndrome (CRS) has been widely recognized, including a series of diseases involving the heart and kidney.7,8 Acute or chronic dysfunction of the heart or kidney may lead to acute or chronic dysfunction of another organ. In 2019, the American Heart Association issued a scientific statement on the classification, pathophysiology, diagnosis, and treatment strategy of CRS, which was divided into 5 subtypes.8 This is very important for the prognosis of patients with type 1 CRS by early detection and the treatment of renal dysfunction in patients with ACS. However, traditional laboratory indicators for kidney function, such as blood urea nitrogen and creatinine, are limited in the early diagnosis of acute kidney injury (AKI) because of their low sensitivity and specificity.9 In addition, diuretic treatment for acute heart failure (AHF) makes the evaluation of renal function more complicated. Recent studies have revealed that markers targeted for renal tubular injury have better early evaluation significance for patients with AKI, especially for patients with AHF, than traditional laboratory indicators. Among them, neutrophil gelatinase–associated lipocalin [neutrophil gelatinase–associated lipocalin (NGAL)], urinary kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18) are increased in the early stage in patients with AKI and can be used as biological markers of early renal dysfunction.10,11 However, the role of these renal tubular injury markers in type 1 CRS has not been clearly studied. Nicorandil can significantly alleviate the occurrence of angina pectoris,12 reduce the incidence of cardiovascular events, and improve the prognosis in patients with ACS. In patients with heart failure, nicorandil could reduce all-cause mortality, increase cardiac pump function,13 and improve left ventricular diastolic function.14 These protective effects of nicorandil might result from the dual vasodilation of coronary and peripheral arteries to increase coronary blood flow, reduce preload and afterload, and alleviate myocardial injury and cardiac remodeling.15 In addition, some studies have found that nicorandil can provide additional renal protection for chronic kidney disease or significantly reduce the incidence of contrast-induced nephropathy in patients undergoing coronary angiography or percutaneous coronary intervention.16 The possible mechanism of nicorandil is the reduction of vascular and renal dysfunction17 or the neutralization of nephrotoxicity by normalizing the TLR4/MAPK P38/NFκ-B inflammatory cascade.18 Moreover, oral nicorandil reduced cardiac death in hemodialysis patients undergoing coronary revascularization.19 Therefore, it is very interesting to study the effect of nicorandil on renal function in patients with type 1 CRS. This study will explore the effect of nicorandil on cardiac and renal function in Chinese patients with type I CRS caused by ACS.

Chronic kidney disease (CKD) is a major contributor to the development of heart failure with preserved ejection fraction (HFpEF), whereas the underlying mechanism of cardiorenal HFpEF is still elusive. The aim of this study was to investigate the role of cardiac fibrosis in a rat model of cardiorenal HFpEF and explore whether treatment with Telmisartan, an inhibitor of renin-angiotensin-aldosterone system (RAAS), can ameliorate cardiac fibrosis and preserve diastolic function in cardiorenal HFpEF. Male rats were subjected to 5/6 subtotal nephrectomy (SNX) or sham operation (Sham), and rats were allowed four weeks to recover and form a stable condition of CKD. Telmisartan or vehicle was then administered p.o. (8 mg/kg/d) for 12 weeks. Blood pressure, brain natriuretic peptide (BNP), echocardiography, and cardiac magnetic resonance imaging were acquired to evaluate cardiac structural and functional alterations. Histopathological staining, real-time polymerase chain reaction (PCR) and western blot were performed to evaluate cardiac remodeling. SNX rats showed an HFpEF phenotype with increased BNP, decreased early to late diastolic transmitral flow velocity (E/A) ratio, increased left ventricular (LV) hypertrophy and preserved ejection fraction (EF). Pathology revealed increased cardiac fibrosis in cardiorenal HFpEF rats compared with the Sham group, while chronic treatment with Telmisartan significantly decreased cardiac fibrosis, accompanied by reduced markers of fibrosis (collagen I and collagen III) and profibrotic cytokines (α-smooth muscle actin, transforming growth factor-β1, and connective tissue growth factor). In addition, myocardial inflammation was decreased after Telmisartan treatment, which was in a linear correlation with cardiac fibrosis. Telmisartan also reversed LV hypertrophy and E/A ratio, indicating that Telmisartan can improve LV remodeling and diastolic function in cardiorenal HFpEF. In conclusion, cardiac fibrosis is central to the pathology of cardiorenal HFpEF, and RAAS modulation with Telmisartan is capable of alleviating cardiac fibrosis and preserving diastolic dysfunction in this rat model.

Instituto de Salud Carlos III FIS/Fondos FEDER (PI17/01093, PI17/01193, CP15/00129, CPII20/00022, PI18/01366, PI19/00588, PI19/00815, PI20/00763, DTS18/00032) ERA-PerMedJTC2018 (KIDNEY ATTACK AC18/00064 and PERSTIGAN AC18/00071, ISCIII-RETIC REDinREN RD016/0009) Sociedad Española de Nefrología, FRIAT, Comunidad de Madrid en Biomedicina (B2017/BMD-3686 CIFRA2- CM) 35.855 JCR (2021) Q1, 3/143 Cardiac & Cardiovascular Systems 4.118 SJR (2021) Q1, 9/356 Cardiology and Cardiovascular Medicine No data IDR 2021 UEM

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

Chronic kidney disease (CKD) and cardiovascular disease (CVD) have an estimated 700-800 and 523 million cases worldwide, respectively, with CVD being the leading cause of death in CKD patients. The pathophysiological interplay between the heart and kidneys is defined as the cardiorenal syndrome (CRS), in which worsening of kidney function is represented by increased plasma concentrations of uremic toxins (UTs), culminating in dialysis patients. As there is a high incidence of CVD in CKD patients, accompanied by arrhythmias and sudden cardiac death, knowledge on electrophysiological remodeling would be instrumental for understanding the CRS. While the interplay between both organs is clearly of importance in CRS, the involvement of UTs in pro-arrhythmic remodeling is only poorly investigated, especially regarding the mechanistic background. Currently, the clinical approach against potential arrhythmic events is mainly restricted to symptom treatment, stressing the need for fundamental research on UT in relation to electrophysiology. This review addresses the existing knowledge of UTs and cardiac electrophysiology, and the experimental research gap between fundamental research and clinical research of the CRS. Clinically, mainly absorbents like ibuprofen and AST-120 are studied, which show limited safe and efficient usability. Experimental research shows disturbances in cardiac electrical activation and conduction after inducing CKD or exposure to UTs, but are scarcely present or focus solely on already well-investigated UTs. Based on UTs data derived from CKD patient cohort studies, a clinically relevant overview of physiological and pathological UTs concentrations is created. Using this, future experimental research is stimulated to involve electrophysiologically translatable animals, such as rabbits, or in vitro engineered heart tissues.

Patients with acute decompensated heart failure (ADHF) show cardiorenal syndrome type 1 (CRS-1) are more likely to have a poor outcome. However, the current criteria often lead to delayed CRS-1 diagnosis. Therefore, we evaluated the predictive value of plasma proenkephalin (pPENK) and urine NT-proBNP (uNT-proBNP) for early diagnosis of CRS-1 and vulnerable-phase prognosis in ADHF patients.The plasma NT-proBNP (pNT-proBNP), pPENK, and uNT-proBNP were measured in 121 ADHF patients on admission. The plasma neutrophil gelatinase-associated lipocalin (pNGAL) was chosen as the reference. Logistic regression was used to determine the predictors of CRS-1. The area under the receiver operating curves (ROCs) was calculated to assess the early diagnostic value of pNGAL, pPENK, and uNT-proBNP/uCr for CRS-1. To evaluate the prognostic risk of factors for the 90-d outcomes of all ADHF patients, the Cox regression was performed and the cumulative risk curve was plotted.We found that pPENK [OR 1.093 (95% CI 1.022-1.169),The newly found pPENK and noninvasive test of uNT-proBNP/uCr ratio (pg/nmol) on admission may be two promising novel predictive biomarkers for early diagnosis of CRS-1 occurrence and vulnerable-phase outcomes in ADHF patients.

Purpose of Review Since CRS is critically dependent on right heart function and involved in interorgan crosstalk, assessment and monitoring of both right heart and kidney function are of utmost importance for clinical outcomes. This systematic review aims to comprehensively report on novel diagnostic and therapeutic paradigms that are gaining importance for the clinical management of the growing heart failure population suffering from CRS. Recent Findings Cardiorenal syndrome (CRS) in patients with heart failure is associated with poor outcome. Although systemic venous congestion and elevated central venous pressure have been recognized as main contributors to CRS, they are often neglected in clinical practice. The delicate hemodynamic balance in CRS is particularly determined by the respective status of the right heart. Summary The consideration of hemodynamic and CRS profiles is advantageous in tailoring treatment for better preservation of renal function. Assessment and monitoring of right heart and renal function by known and emerging tools like renal Doppler ultrasonography or new biomarkers may have direct clinical implications.

Several studies have shown that cholecalciferol supplementation (25OHD-S) in chronic kidney disease (CKD) improves kidney injury by reducing fibrosis-related vascular calcification and declining apoptosis-linked nephron damage.The oral 25OHD-S was evaluated in 60,000 IU/month/36 weeksVitamin D deficiency alters in the same manner CMet, CRenal, and others biomarkers in both groups SS; however, these disorders are more acute in blacks compared to whites SS. Oral 25OHD-S a highlighted improvement of eGFR drop, SHPT decrease, decline proteinuria, and cardiac failure risk (NT-proBNP and cTnT) attenuation. Concomitantly, 25OHD-S normalizesThe oral vitamin D3 supplementation, according the dose, and the treatment duration does not like in black-skinned people

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

Severe acute respiratory syndrome coronavirus 2 has rapidly spread worldwide and resulted in the coronavirus disease 2019 (COVID-19) pandemic. The disease raised an unprecedented demand for intensive care support due to severe pulmonary dysfunction and multiorgan failure. Although the pulmonary system is the potential target of the COVID-19, recent reports have demonstrated that COVID-19 profoundly influences the cardiovascular system and the kidneys. Research studies on cadavers have shown that direct heart and kidney injury can be frequently seen in patients deceased due to COVID-19 infection. On the other hand, functional or structural dysfunction of the heart may deteriorate the renal function and vice versa. This concept is already known as the cardiorenal syndrome and may play a role in COVID-19. Proactive monitoring of micro- and macrohemodynamics could allow prompt correction of circulatory dysfunction and can be of pivotal importance in the prevention of acute kidney injury. Moreover, type and amount of fluid therapy and vasoactive drug support could help manage these patients either with or without mechanical ventilator support. This brief review outlines the current evidence regarding the COVID-19-related renal and cardiorenal complications and discusses potential hemodynamic management strategies.

Supplemental Digital Content is available in the text., Acute decompensated heart failure (ADHF) is one of the leading admission diagnoses worldwide, yet it is an entity with incompletely understood pathophysiology and limited therapeutic options. Patients admitted for ADHF have high in-hospital morbidity and mortality, as well as frequent rehospitalizations and subsequent cardiovascular death. This devastating clinical course is partly due to suboptimal medical management of ADHF with persistent congestion upon hospital discharge and inadequate predischarge initiation of life-saving guideline-directed therapies. While new drugs for the treatment of chronic HF continue to be approved, there has been no new therapy approved for ADHF in decades. This review will focus on the current limited understanding of ADHF pathophysiology, possible therapeutic targets, and current limitations in expanding available therapies in light of the unmet need among these high-risk patients.

Cardiorenal syndrome (CRS) is defined by coexisting heart and renal dysfunctions. Malfunction of 1 organ may cause dysfunction of the other with variable causative disease that defines the type of CRS (1–5). Numerous studies showed that the prevalence of cardiovascular disease is increased in patients with chronic kidney disease (CKD). Similarly, CKD affects a large proportion of patients with heart failure. This overlap between primary heart or primary kidney disease blurs cause–effect inferences of the initiator/target organ. The classical subdivision of CRS in 5 categories does not provide pathophysiological suggestions for targeted intervention. It seems timely to revisit the value of CRS biomarkers in a pathophysiology-centered approach. We systematically reviewed the literature in CRS, which revealed 53 clinical studies describing the use of 44 biomarkers and 4 proteomic panels. All biomarkers are involved in at least one of the CRS comorbidities. Among the pathways affected, inflammation, aberrant glucose metabolism, neurohormonal activation, and oxidative stress are well described. There is growing evidence that fibrosis may be the “cornerstone” that unifies most of the pathways leading to CRS. Formation of excess fibrous connective tissue antedates CRS in many cases. This review highlights that biomarkers reflecting fibrosis may be of substantial clinical value in the early detection, prognostication, and guiding treatment of CRS. Biomarkers detecting changes in collagen turnover in the extracellular matrix of heart and kidney appear able to depict subclinical changes in the fibrotic remodeling of tissues and constitute a promising approach toward personalized intervention in CRS.

Ischemic heart disease is the leading cause of death worldwide and is frequently comorbid with chronic kidney disease. Physiological communication is known to occur between the heart and the kidney. Although primary dysfunction in either organ can induce dysfunction in the other, a clinical entity known as cardiorenal syndrome, mechanistic details are lacking. Here, we used a model of experimental myocardial infarction (MI) to test effects of chronic cardiac ischemia on acute and chronic kidney injury. Surprisingly, chronic cardiac damage protected animals from subsequent acute ischemic renal injury, an effect that was accompanied by evidence of chronic kidney hypoxia. The protection observed post-MI was similar to protection observed in a separate group of healthy animals housed in ambient hypoxic conditions prior to kidney injury, suggesting a common mechanism. There was evidence that chronic cardiac injury activates renal hypoxia-sensing pathways. Increased renal abundance of several glycolytic enzymes following MI suggested that a shift toward glycolysis may confer renal ischemic preconditioning. In contrast, effects on chronic renal injury followed a different pattern, with post-MI animals displaying worsened chronic renal injury and fibrosis. These data show that although chronic cardiac injury following MI protected against acute kidney injury via activation of hypoxia-sensing pathways, it worsened chronic kidney injury. The results further our understanding of cardiorenal signaling mechanisms and have implications for the treatment of heart failure patients with associated renal disease. NEW & NOTEWORTHY Experimental myocardial infarction (MI) protects from subsequent ischemic acute kidney injury but worsens chronic kidney injury. Observed protection from ischemic acute kidney injury after MI was accompanied by chronic kidney hypoxia and increased renal abundance of hypoxia-inducible transcripts. These data support the idea that MI confers protection from renal ischemic injury via chronic renal hypoxia and activation of downstream hypoxia-inducible signaling pathways.

Background and Aims: Anemia is a common complication of heart failure and Chronic Kidney Disease (CKD). Sacubitril-valsartan is a novel therapy for the treatment of chronic Heart Failure with a reduced Ejection Fraction (HFrEF). We have evaluated the short-term effects of sacubitril- valsartan on the anemia of CRS. Methods: The study group comprised 39 patients with HFrEF, who were followed-up for three months. The study is a retrospective analysis of clinical data. Data of 3 months’ and baseline visits were recorded including plasmatic creatinine, glomerular filtration rate, cystatin C, kaliemia, haemoglobin, pro-BNP, and albuminuria. Results: In all, 34 patients ended the follow-up. Mean sacubitril-valsartan dosage at baseline was 101 ± 62 mg/day and 126 ± 59 mg/day at end. Mean hemoglobin increased from 12.2 ± 1.1 g/dl at baseline to 12.9 ± 1.0 g/dl (p = 0.001,). Prevalence of anemia was 64.7% (95%CI, 47.9-78.5%) at baseline and 38.4 (95%CI, 23.9-55.0%) after the follow-up (p = 0.016). Serum cystatin C levels decreased from 2.71 ± 1.0 to 2.48 ± 1.0 mg/l (p = 0.028). Serum K levels remained unchanged (baseline 4.94 ± 0.60, three months visit 4.94 ± 0.61 mmol/l, p = 0.998). Conclusions: Sacubitril-valsartan improves anemia in CRS patients. An improvement in serum cystatin levels was observed. Few untoward effects were detected. These findings should be confirmed in wider clinical trials.

Cardiorenal syndrome is a clinical condition that impacts both the heart and the kidneys. One organ's chronic or acute impairment can lead to the other's chronic or acute dysregulation. The cardiorenal syndrome has been grouped into five subcategories that describe the etiology, pathophysiology, duration, and pattern of cardiac and renal dysfunction. This classification reflects the large spectrum of interrelated dysfunctions and underlines the bidirectional nature of heart-kidney interactions. However, more evidence is needed to apply these early findings in medical practice. Understanding the relationship between these two organs during each organ's impairment has significant clinical implications that are relevant for therapy in both chronic and acute conditions. The epidemiology, definition, classification, pathophysiology, therapy, and outcome of each form of cardiorenal syndrome are all examined in this review.

The cardiorenal nexus encompasses a bidirectional relationship between the heart and the kidneys. Chronic abnormalities in cardiac function can lead to progressive kidney disease, and chronic kidney disease can lead to progressively decreasing cardiac function and increasing risk of cardiovascular disease, including heart failure. About 15% of US adults have chronic kidney disease, 2% have heart failure, and 9% have cardiovascular disease. Prevalence rates of chronic kidney disease, cardiovascular disease, and associated morbidities such as type 2 diabetes are expected to increase with an aging population. Observational studies provide evidence for the cardiorenal nexus. Follow‐up data from placebo arms of clinical trials in chronic kidney disease or cardiovascular disease show higher rates of renal and cardiovascular outcome events in patient subgroups with type 2 diabetes than in those without type 2 diabetes. The cardiorenal syndromes develop along an interlinked pathophysiological trajectory that requires a holistic, collaborative approach involving a multidisciplinary team. There is now a compendium of treatment options. Greater understanding of the underlying pathophysiology of the cardiorenal nexus will support optimization of the management of these interlinked disease states.

The end-stage of the clinical combination of heart failure and kidney disease has become known as cardiorenal syndrome. Adverse consequences related to diabetes, hyperlipidemia, obesity, hypertension and renal impairment on cardiovascular function, morbidity and mortality are well known. Guidelines for the treatment of these risk factors have led to the improved prognosis of patients with coronary artery disease and reduced ejection fraction. Heart failure hospital admissions and readmission often occur, however, in the presence of metabolic, renal dysfunction and relatively preserved systolic function. In this domain, few advances have been described. Diabetes, kidney and cardiac dysfunction act synergistically to magnify healthcare costs. Current therapy relies on improving hemodynamic factors destructive to both the heart and kidney. We consider that additional hemodynamic solutions may be limited without the use of animal models focusing on the cardiomyocyte, nephron and extracellular matrices. We review herein potential common pathophysiologic targets for treatment to prevent and ameliorate this syndrome.

KidneyIntelX, a bioprognostic test for assessing risk of CKD progression, risk stratified individuals for kidney, heart failure, and death outcomes in the Canagliflozin Cardiovascular Assessment Study. Individuals scored as high risk seemed to derive more of benefit from treatment with canagliflozin versus placebo. These findings may serve to increase adoption of underutilized therapies for cardiorenal risk reduction in patients with diabetic kidney disease.

Heart failure can lead to renal impairment, an interaction now termed "cardiorenal syndrome." The prevalent physiological explanation for the renal impairment that accompanies heart failure centers around the forward failure hypothesis, which emphasizes the role of left ventricular dysfunction in causing edema, and the backward failure hypothesis, which singles out venous congestion as the dominant mechanism of edema and reduced glomerular filtration rate. In this review, we provide an appraisal on venous congestion, an extremely important contributor that has received little attention. We also summarize the pharmacology of loop diuretics, explain current understanding of diuretic resistance, and address controversies regarding decongestive treatments.

Calcium sensing receptor (CaSR) is localized in various organs and plays diverse physiological and pathological roles. Several scientific contributions have suggested the involvement of this cell surface receptor in cardiac and renal diseases. Sepsis is considered to be one of the major causes of ICU admissions. Cardiac dysfunction and acute kidney injury are major manifestations of sepsis and associated with reduced survival. Presently, the treatment approaches for management of sepsis induced cardiac depression and kidney injury are not satisfactory. Activation of CaSR has been demonstrated to induce cardiomyocyte damage upon lipopolysaccaharde (LPS) exposure by enhancing calcium ion levels, ROS (reactive oxygen species) production, promotion of inflammation and apoptosis. In addition, CaSR seems to be a critical regulator of intracellular calcium ion levels, which is directly implicated in induction of mitochondrial dysfunction and release of various pro-apoptotic pathways during sepsis. Certain evidences have also documented the expression of CaSR on neutrophils and T lymphocytes, where it is involved in activation of neutrophils and induces apoptosis of immune cells. Moreover, the expression of CaSR has been confirmed in podocytes, mesangial cells, proximal tubular cells and its activation is responsible for podocyte effacement, mesangial cell proliferation and proximal tubular cell apoptosis. We have analyzed the existing evidences, and critically discussed the possible mechanisms underlying CaSR activation mediated cardiac and renal dysfunction in sepsis condition.

Venous congestion has emerged as an important cause of renal dysfunction in patients with cardiorenal syndrome. However, only limited progress has been made in differentiating this haemodynamic phenotype of renal dysfunction, because of a significant overlap with pre‐existing renal impairment due to long‐term hypertension, diabetes, and renovascular disease. We propose congestive nephropathy (CN) as this neglected clinical entity. CN is a potentially reversible subtype of renal dysfunction associated with declining renal venous outflow and progressively increasing renal interstitial pressure. Venous congestion may lead to a vicious cycle of hormonal activation, increased intra‐abdominal pressure, excessive renal tubular sodium reabsorption, and volume overload, leading to further right ventricular (RV) stress. Ultimately, renal replacement therapy may be required to relieve diuretic‐resistant congestion. Effective decongestion could preserve or improve renal function. Congestive acute kidney injury may not be associated with cellular damage, and complete renal function restoration may be a confirmatory diagnostic criterion. In contrast, a persistently low renal perfusion pressure might induce renal dysfunction and histopathological lesions with time. Thus, urinary markers may differ. CN is mostly seen in biventricular heart failure but may also occur secondary to pulmonary arterial hypertension and elevated intra‐abdominal pressure. An increase in central venous pressure to >6 mmHg is associated with a steep decrease in glomerular filtration rate. However, the central venous pressure range that can provide an optimal balance of RV and renal function remains to be determined. We propose criteria to identify cardiorenal syndrome subgroups likely to benefit from decongestive or pulmonary hypertension‐specific therapies and suggest areas for future research.

Background. Primary hyperparathyroidism (PHPT) is an endocrine disease, due to the formation of excess parathyroid hormone secretion and a disturbance of phosphorus-calcium metabolism. PHPT is associated with reduced renal function and related increased mortality, therefore renal function impairment defined as a glomerular filtration rate (GFR) less than 60 mL/ min/1.73 m 2 is considered as an indication for surgical treatment. Some patients with PHPT have secondary cardio-renal syndrome (type 5), which is characterized by the presence of combined renal and cardiac pathology. THE AIM: Evaluate the GFR in patients with mild and symptomatic PHPT and its changes after parathyroidectomy and on medical treatment. Patients and methods : A cross-sectional comparative and prospective study was conducted on 100 patients with confirmed PHPT. A clinical and laboratory examination was performed at 6, 12, and/or 24 months and included an assessment of the PHPT complications as well as expression of cardio-renal syndrome according to the selected management tactics. Changes in GFR were evaluated in 29 patients after surgical treatment and in 27 patients on conservative management. Glomerular filtration rate was calculated by the Modification of Diet in Renal Disease Study (MDRD) formula. The chronic kidney disease (CKD) stage was estimated accordingly to current recommendations. Results: We included 100 patients (10 men and 90 women) with PHPT: 33 with mild and 67 with symptomatic PHPT. The median age was 57 years [51;61]. Mean GFR was 84,1 [73,3; 97,9] ml/ min/1,73 m 2 . Prevalence of CKD 3-4 in patients with PHPT was recorded at 11 %. Patient management tactics were determined in accordance with international recommendations. In the long-term period after surgery, we observed the decrease of GFR in patients with mild form within the limits of CKD 1-2 (p=0,013, W-test). No significant changes in GFR were noted during medical management and monitoring. Summary, the cardio-renal syndrome (CKD of any stage and cardiovascular pathology) was revealed in 26 % of patients. Arterial hypertension was registered in 40 %. Conclusions : We found a high frequency of renal function impairment in patients with PHPT, including patients with a mild form of the disease. We did not observe any significant improvement in renal filtration function, after surgical treatment and remission of PHPT. The safety of conservative tactics has been confirmed. The high frequency of cardiovascular pathology in patients with PHPT is beyond doubt and requires prospective studies in the larger cohorts of patients.

Right ventricular (RV) dysfunction induced type II cardiorenal syndrome (CRS) has a high mortality rate, but little attention has been paid to this disease, and its unique molecular characteristics remain unclear. This study aims to investigate the transcriptomic expression profile in this disease and identify key RNA pairs that regulate related molecular signaling networks. We established an RV dysfunction-induced type II CRS mouse model by pulmonary artery constriction (PAC). PAC mice developed severe RV hypertrophy and fibrosis; renal atrophy and dysfunction with elevated creatinine were subsequently observed. Expression profiles in RV and kidney tissues were obtained by whole transcriptome sequencing, revealing a total of 741 and 86 differentially expressed (DE) mRNAs, 159 and 29 DEmiRNAs and 233 and 104 DEcircRNAs between RV and kidney tissue, respectively. Competing endogenous RNA (ceRNA) networks were established. A significant alteration in proliferative, fibrotic and metabolic pathways was found based on GO and KEGG analyses, and the network revealed key ceRNA pairs, such as novel_circ_002631/miR-181a-5p/Creb1 and novel_circ_002631/miR-33-y/Kpan6. These findings indicate that significantly dysregulated pathways in RV dysfunction induced type II CRS include Ras, PI3K/Akt, cGMP-PKG pathways, and thyroid metabolic pathways. These ceRNA pairs can be considered potential targets for the treatment of type II CRS.

Introduction: The aim of the study was to demonstrate the outcomes of peritoneal dialysis (PD) in critically ill cardiorenal syndrome type 1 (CRS1). Methods: A cohort of 147 patients with CRS1 who received PD from 2011 to 2019 in a referral hospital in Thailand was analyzed. The primary outcome was 30-day in-hospital mortality. Ultrafiltration and net fluid balance among survivors and nonsurvivors in the first 5 PD sessions were compared. Results: The 30-day mortality rate was 73.4%. Most patients were critically ill CRS1 (all patients had a respiratory failure of which 68% had cardiogenic shock). Blood urea nitrogen and creatinine at the commencement of PD were 60.1 and 4.05 mg/dL. In multivariable analysis, increasing age, unstable hemodynamics, and positive fluid balance in the first 5 PD sessions were associated with the risk of in-hospital mortality. The change of fluid balance per day during the first 5 dialysis days was significantly different among survivor and nonsurvivor groups (−353 vs. 175 mL per day, p = 0.01). Conclusions: PD is a viable dialysis option in CRS1, especially in a resource-limited setting. PD can save up to 27% of lives among patients with critically ill CRS1.

Background: Recent research highlighted the potential role of circulating cell-free DNA (cfDNA), resulted by apoptosis or cell necrosis, as a prognostic marker in the setting of different clinical conditions. Cardiorenal syndrome type 1 (CRS type 1) is characterized by a rapid worsening of cardiac function leading to acute kidney injury (AKI). Apoptosis of renal epithelial cells is proposed as a mechanism involved in CRS type 1. In this study, we investigated cfDNA levels in patients with acute heart failure (AHF) and CRS type 1 and the possible correlation between cfDNA levels and inflammatory and apoptotic parameters. Methods: We enrolled 17 AHF patients and 15 CRS type 1 who exhibited AKI at the time of admission (caused by AHF) or developed AKI during the first 48 h from admission. cfDNA was extracted from plasma and quantified by real-time polymerase chain reaction. Plasma levels of NGAL, tumor necrosis factor-α, interleukin (IL)-6, IL-18, and caspase-3 were measured. Results: We observed significantly higher levels of cfDNA in patients with CRS type 1 than patients with AHF. Caspase-3, IL-6, IL-18, and NGAL levels resulted significantly increased in patients with CRS type 1. Moreover, a positive correlation between cfDNA levels and caspase-3 levels was found, as well as between cfDNA levels and IL-6 and renal parameters. Conclusion: Our study explores the premise of cfDNA as a marker for apoptosis and inflammation in CRS type 1 patients. cfDNA could potentially serve as an index for noninvasive monitoring of tissue damage and apoptosis in patients with AKI induced by AHF.

Introduction: Optimal method for noninvasive assessment of venous congestion remains an unresolved issue. Portal vein (PV) and intrarenal venous flow alterations are markers of abdominal venous congestion and have been associated with acute kidney injury (AKI) in cardiac surgery patients. It is currently unknown if portal vein flow (PVF) alterations in heart failure can be reversed with diuretic treatment and track decongestion. Objective: The aim of this study is to evaluate PVF alterations in patients with ADHF at arrival and after decongestive treatment. Methods: Assessment of venous congestion using point-of-care ultrasound was performed in 12 patients with ADHF (6 patients with left-sided heart failure and 6 patients with right-sided heart failure). Evaluation included inferior vena cava (IVC) size and collapsibility in addition to PV Doppler to determine pulsatility fraction (PF). Results: Increased PV PF (81.75 ± 13%) was found on admission. After effective decongestive treatment, it improved to (17.43 ± 2.2%). Improvement in IVC size and collapsibility was seen in most patients with left-sided heart failure and none of the patients with right-sided heart failure. Improvement in PV PF coincided with return to baseline of Serum Cr in patients that presented with AKI. Conclusions: Evaluation of abdominal venous congestion by point-of-care ultrasound could aid in diagnosis and follow-up of patients with congestive kidney injury.

Elevated sympathetic vasomotor activity is a common feature of cardiorenal diseases. Therefore, the sympathetic nervous system is an important therapeutic target, particularly the fibers innervating the kidneys. In fact, renal denervation has been applied clinically and shown promising results in patients with hypertension and chronic kidney disease. However, the underlying mechanisms involved in the cardiorenal protection induced by renal denervation have not yet been fully clarified. This mini-review highlights historical and recent aspects related to the role of renal sensory fibers in the control of cardiorenal function under normal conditions and in experimental models of cardiovascular disease. Results have demonstrated that alterations in renal sensory function participate in the maintenance of elevated sympathetic vasomotor activity and cardiorenal changes; as such, renal sensory fibers may be a potential therapeutic target for the treatment of cardiorenal diseases. Although it has not yet been applied in clinical practice, selective afferent renal denervation may be promising, since such an approach maintains efferent activity and can provide more refined control of renal function compared with total renal denervation. However, more studies are needed to understand the mechanisms by which renal afferents partially contribute to such changes, in addition to the need to evaluate the safety and advantages of the approach for application in the clinical practice.

Cardiovascular disease (CVD) is a major cause of death in patients with chronic kidney disease (CKD). Both conditions are rising in incidence as well as prevalence, creating poor outcomes for patients and high healthcare costs. Recent data suggests CKD to be an independent risk factor for CVD. Accumulation of uremic toxins, chronic inflammation, and oxidative stress have been identified to act as CKD-specific alterations that increase cardiovascular risk. The association between CKD and cardiovascular mortality is markedly influenced through vascular alterations, in particular atherosclerosis and vascular calcification (VC). While numerous risk factors promote atherosclerosis by inducing endothelial dysfunction and its progress to vascular structural damage, CKD affects the medial layer of blood vessels primarily through VC. Ongoing research has identified VC to be a multifactorial, cell-mediated process in which numerous abnormalities like mineral dysregulation and especially hyperphosphatemia induce a phenotype switch of vascular smooth muscle cells to osteoblast-like cells. A combination of pro-calcifying stimuli and an impairment of inhibiting mechanisms like fetuin A and vitamin K-dependent proteins like matrix Gla protein and Gla-rich protein leads to mineralization of the extracellular matrix. In view of recent studies, intercellular communication pathways via extracellular vesicles and microRNAs represent key mechanisms in VC and thereby a promising field to a deeper understanding of the involved pathomechanisms. In this review, we provide an overview about pathophysiological mechanisms connecting CKD and CVD. Special emphasis is laid on vascular alterations and more recently discovered molecular pathways which present possible new therapeutic targets.

Background: This study aims to analyse whether in acute heart failure (AHF) with iron deficiency (ID), the administration of ferric carboxymaltose (FCM) produces a greater benefit in renal dysfunction. Methods: A total of 812 consecutive patients admitted for AHF and ID were studied. Untreated (n:272) and treated (n:540) patients were compared. The six-month prevalence of a combined event (readmission for HF, all-cause death, and emergency department visit for decompensation) was analysed. Three grades of renal dysfunction (KDIGO) were compared, Group 1 (grades 1 and 2), Group 2 (grades 3a and 3b), and Group 3 (grades 4 and 5). Results: There were differences in sex distribution (untreated group: males 39.7% vs. treated group: males 51.9%; p < 0.001). Sex-adjusted combined event analysis showed a greater benefit in Group 1 (OR: 0.31, 95% CI:0.19–0.5; p < 0.001) and Group 2 (OR: 0.23, 95% CI:0.14–0.38; p < 0.001), but not in Group 3 (OR: 0.51, 95% CI:0.17–0.55; p: 0.237). Conclusions: The administration of FCM in patients with AHF and ID reduces the combined event analysed. The benefit is greater when renal dysfunction is present, except in very advanced degrees where no significant benefit is obtained.

Sacubitril/valsartan (Sac/Val), a combined angiotensin-II receptor blocker (Val) and neprilysin inhibitor (Sac) in a 1:1 molar ratio, was shown to decrease the risk of cardiovascular death or heart failure (HF) hospitalization in patients with HF and reduced left ventricular (LV) ejection fraction. This study examined the effects of Sac/Val on LV structure, function, and bioenergetics, and on biomarkers of kidney injury and kidney function in dogs with experimental cardiorenal syndrome.Fourteen dogs with cardiorenal syndrome (coronary microembolization-induced HF and renal dysfunction) were randomized to 3 months Sac/Val therapy (100 mg once daily, n = 7) or no therapy (control, n = 7). LV ejection fraction and troponin-I, as well as biomarkers of kidney injury/function including serum creatinine and urinary kidney injury molecule-1 were measured before and at end of therapy and the change (treatment effect change) calculated. Mitochondrial function measures, including the maximum rate of adenosine triphosphate synthesis, were measured in isolated cardiomyocytes at end of therapy. In Sac/Val dogs, the change in ejection fraction increased compared with controls, 6.9 ± 1.4 vs 0.7 ± 0.6%, P.002, whereas change in troponin I decreased, -0.16 ± 0.03 vs -0.03 ± 0.02 ng/mL, P.001. Urinary change in kidney injury molecule 1 decreased in Sac/Val-treated dogs compared with controls, -17.2 ± 7.9 vs 7.7 ± 3.0 mg/mL, P.007, whereas the change in serum creatinine was not significantly different. Treatment with Sac/Val increased adenosine triphosphate synthesis compared with controls, 3240 ± 121 vs 986 ± 84 RLU/µg protein, P.05.In dogs with cardiorenal syndrome, Sac/Val improves LV systolic function, improves mitochondrial function and decreases biomarkers of heart and kidney injury. The results offer mechanistic insights into the benefits of Sac/Val in HF with compromised renal function.

The cardiovascular and renal systems share an intimate physiological relationship, wherein a perturbance in one system may have an adverse effect on the other. Since the burden of renal disease increases with age, there is a considerable interest in the pathophysiology of kidney disease in the geriatric patient population. This review will explore the physiological dynamics behind the increased susceptibility to kidney disease in this population. A better understanding of these pathophysiological changes may lead to improved prevention and management strategies.

Almost half of hospitalised patients with acute heart failure develop acute cardiorenal syndrome. Treatment consists of optimisation of fluid status and haemodynamics, targeted therapy for the underlying cardiac disease, optimisation of heart failure treatment and preventive measures such as avoidance of nephrotoxic agents. Renal replacement therapy may be temporarily needed to support kidney function, mostly in case of diuretic resistant fluid overload or severe metabolic derangement. The best timing to initiate renal replacement therapy and the best modality in acute heart failure are still under debate. Several modalities are available such as intermittent and continuous renal replacement therapy as well as hybrid techniques, based on two main principles: haemofiltration and haemodialysis. Although continuous techniques have been associated with less haemodynamic instability and a greater chance of renal recovery, cohort data are conflicting and randomised controlled trials have not shown a difference in recovery or mortality. In the presence of diuretic resistance, isolated ultrafiltration with individualisation of ultrafiltration rates is a valid option for decongestion in acute heart failure patients. Practical tools to optimise the use of renal replacement therapy in acute heart failure-related acute cardiorenal syndrome were discussed.

Patients with diabetes mellitus (DM) often present other chronic comorbidities including arterial hypertension (AH), chronic kidney disease (CKD), ischemic heart disease (IHD) and heart failure with preserved ejection fraction (HFpEF). The frequent association of the latter conditions is considered part of the spectrum of cardio-renal syndromes (CRS), a group of disorders of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. Verapamil is a non-dihydropyridine calcium channel blocker (CCB) widely used in the treatment of hypertension, chronic stable angina, secondary prevention of reinfarction, paroxysmal supra-ventricular tachycardia and for rate control in atrial fibrillation/flutter. In addition to its antihypertensive and anti-ischemic actions verapamil exerts favorable effects also on glycemic control, proteinuric diabetic nephropathy, left ventricular diastolic dysfunction and sympathetic nervous system overactivity which may potentially benefit patients with DM and CRS. In this narrative review, we summarize the current evidence on the potential role of verapamil in the prevention and treatment of CRS in diabetic hypertensive patients.

Cardio-renal syndrome (CRS) denotes the convergence of heart-kidney interactions across several mechanisms. The current study is conducted to evaluate the anti-inflammatory role of adipose tissue-derived stem cells (ASCs) versus adipose stem cell-derived extracellular vesicles (ADSCs-EVs) in experimental model of cardiorenal syndrome type III. The study was conducted on 50 male rats that were equally divided to: group I (control group); Group II (experimental cardiorenal syndrome group) which induced by right renal artery ligation (ICRSIII); Group III (Sham-operated control group) which underwent surgical incision without renal artery ligation; Group IV (ICRSIII which received ADSCs-extracellular vesicles (ADSCs-EVs); Group V (ICRSIII which received adipose tissue stem cells (ASCs). Assessment of pro-inflammatory cytokines; IL-10, IL-1α, IL-6, IL-1 β, IFN-γ, NF-α and their mRNA gene expression quantitation, (NGAL), and brain natriuretic peptide (BNP) as markers of cardiac dysfunction, as well as histopathological examination of renal tissue was examined by HE, Masson trichrome and periodic acid-Schiff stains (PAS). The ICRS group exhibited significant acute tubular injury with tubular dilation, loss of brush borders, epithelial flattening, and occasional sloughed cells in lumen. Use of either ADSCs-EVs or ASCs significantly ameliorated the histological findings of tubular injury. Proinflammatory cytokines, BNP and NGAL were significantly elevated in ICRSIII group as compared to all other studied groups. Administration of ADSCs-EVs or ASCs led to significant decrease in all proinflammatory cytokines as well as BNP and NGAL levels with no significant difference between them. In conclusion, ADSCs-EXs and ASCs exhibited significant repairing effects in experimental-induced cardiorenal syndrome type III as evidenced by amelioration of histological findings of tubular injury, anti-inflammatory effects, and the significant decrease in markers of cardiac dysfunction. ADSC-EVs reprogramed injured cardiac cells by activating regenerative processes.