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This study tested the hypothesis that empagliflozin (EMPA) therapy effectively protected renal and heart functions via downregulating reactive oxygen species (ROS) and activating AMPK signaling in cardiorenal syndrome (CRS) (induced by doxorubicin-5/6 nephrectomy) rats. In vitro result showed that underwent p-Cresol treatment, the H9C2/NRK-52E cell viabilities, were significantly suppressed, whereas cellular levels of ROS and early/late apoptosis of these cells were significantly increased that were significantly reversed by EMPA treatment (all p < 0.001). The protein levels of the cell-stress/oxidative signaling (p-PI3K/p-Akt/p-mTOR/NOXs/p-DRP1) were significantly activated, whereas the mitochondrial biogenesis signaling (p-AMPK/SIRT-1/TFAM/PGC-1α) was significantly repressed in these two cell lines treated by p-Cresol and all of these were significantly reversed by EMPA treatment (all p < 0.001). Male-adult-SD rats were categorized into groups 1 [sham-operated control (SC)]/2 [SC + high protein diet (HPD) since day 1 after CKD induction]/3 (CRS + HPD)/4 (CRS + HPD+EMPA/20 mg/kg/day) and heart/kidney were harvested by day 60. By day 63, the renal function parameters (creatinine/BUN/proteinuria)/renal artery restrictive index/cellular levels of ROS/inflammation were significantly increased in group 3 than in groups 1/2, whereas heart function exhibited an opposite pattern of ROS among the groups, and all of these parameters were significantly reversed by EMPA treatment (all p < 0.0001). The protein levels of inflammation/ oxidative-stress/cell-stress signalings were highest in group 2, lowest in group 1 and significantly lower in group 4 than in group 2, whereas the AMPK-mitochondrial biogenesis displayed an opposite manner of oxidative-stress among the groups (all p < 0.0001). EMPA treatment effectively protected the heart/kidney against CRS damage via suppressing ROS signaling and upregulating AMPK-mediated mitochondrial biogenesis. [ABSTRACT FROM AUTHOR]

Despite a large amount of research on synchronous and mutually induced kidney and heart damage, the basis of the disease is still not fully clarified. Healthy mitochondria are essential for normal kidney and heart function. Mitochondrial dysfunction occurs when the clearance or process of generation and fragmentation of mitochondria is disturbed. The kidney is the second organ after the heart in terms of the number of mitochondria. Kidney tubules are rich in mitochondria due to the high energy requirements for absorption of large amounts of ultrafiltrate and dissolved substances. The place of action of oxidative stress is the influence on the balance in the production and breakdown of the mitochondrial reactive oxygen species. A more precise determination of the place and role of key factors that play a role in the onset of the disease is necessary for understanding the nature of the onset of the disease and the creation of therapy in the future. This underscores the urgent need for further research. The narrative review integrates results found in previously performed studies that have evaluated oxidative stress participation in cardiorenal syndrome type 3. [ABSTRACT FROM AUTHOR]

Cardiorenal syndrome (CRS) is a life-threatening disorder that involves a complex interplay between the two organs. Managing this multifaceted syndrome is challenging in the hospital and requires a multidisciplinary approach to tackle the many manifestations and complications. There is no universally accepted algorithm to treat patients, and therapeutic options vary from one patient to another. The mainstays of therapy involve the stabilization of hemodynamics, decongestion using diuretics or renal replacement therapy, improvement of cardiac output with inotropes, and goal-directed medical treatment with renin–angiotensin–aldosterone system inhibitors, beta-blockers, and other medications. Mechanical circulatory support is another viable option in the armamentarium of agents that improve symptoms in select patients. [ABSTRACT FROM AUTHOR]

As early as the first stages of rheumatic diseases in children, a number of pathological changes occur with the involvement of many organs and systems in the process. In children with juvenile idiopathic arthritis (JIA), decreased adaptability of the cardiovascular system is detected in 17.0-20.0 % of cases. 36.9 % of children with JIA develop renal lesions. Thus, inflammation underlies the interaction between pathological mechanisms of renal and heart failure in patients with rheumatic diseases. The aim of the work is to identify the characteristics of the interaction between main morphofunctional parameters of the cardiovascular system and kidneys in children with JIA, and the factors that give rise to the formation and worsening of these disorders. Materials and methods. 152 patients aged 13.42 ± 0.22 years with JIA were examined. Renal functions were examined based on the levels of creatinine, urea, albuminuria, urine specific gravity, glomerular filtration rate. To determine the morphofunctional parameters of the heart, ultrasound examinations of both left and right ventricles were performed. Results. In children with JIA, the functional parameters of the kidneys almost do not differ from those of the control group, with the exception of albuminuria, which is significantly higher in children of the main group and increases with the process activity progression. Morphofunctional analysis of the cardiac parameters has shown a decrease in the stroke volume of the left ventricle (51.83 ± 1.57 ml against 57.86 ± 2.54 ml, р < 0.05) with preserved ejection fraction and a significant increase in the right ventricle volumes both diastolic (34.54 ± 1.51 ml against 22.45 ± 2.11 ml, p < 0.001) and systolic (19.15 ± 0.96 ml against 10.18 ± 1.14 ml, p < 0.001), as well as stroke volume (15.39 ± 0.84 ml against 12.21 ± 1.05 ml, p < 0.01), with a significant decrease in its ejection fraction (45.04 ± 1.44 % against 56.06 ± 1.59 %, p < 0.001). Conclusions. Renal functional parameters are within normal values, but the level of albuminuria is significantly higher and increases with the process activity progression in children with JIA. The morphofunctional parameters of the left ventricle correspond to the control ones, but there is an increase in the right ventricle volume with a significant decrease in its ejection fraction. A decrease in the myocardial pumping function of the right ventricle is accompanied by a decrease in renal blood supply which leads to the development of cardiorenal syndrome type 5 in JIA children. [ABSTRACT FROM AUTHOR]

In rats with unilateral nephrectomy and cardiac dysfunction, renal function deteriorates at an accelerated rate, as evidenced by increased proteinuria. Whether myocardial infarct-induced heart failure (HF) exacerbates renal injury in hypertensive rats with mild renal injury has not been reported. Rats underwent either coronary ligation or sham surgery. Thirty spontaneously hypertensive rats (SHRs) aged 8 weeks were randomly divided into two groups. Group 1 was the sham group, in which the rats underwent thoracotomy without ligation of the coronary artery. Group 2 underwent coronary artery ligation. The rats in group 2 underwent coronary artery ligation on week 0. The experiment lasted 12 weeks. Urine was collected in metabolic cages over a 24-h period. Urine was collected from the rats 2 days before the end of the experiment, and the ratio of urinary protein to urinary creatinine was measured in the clinical laboratory. All rats were examined by echocardiogram one day before the end of the experiment. On the last day of the experiment, blood was collected and sent to the laboratory for analysis. Hematoxylin–eosin (HE) and periodic acid-Schiff (PAS) staining were performed on heart and kidney sections. The ejection fraction in group 2 was lower than that in group 1 (P < 0.001). The urinary albumin to creatinine ratio in group 2 was greater than that in group 1 (P < 0.001). The urea and creatinine levels in group 1 were significantly lower than those in group 2 (P < 0.01). The levels of brain natriuretic peptide (BNP), neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C were greater in the second group than in the first group (P < 0.05). The interleukin-1β (IL-1β) and interleukin-6 (IL-6) levels in group 2 were significantly greater than those in group 1 (P < 0.001). The malondialdehyde (MDA) levels in Group 2 were greater than those in Group 1 (P < 0.01). The glutathione peroxidase (GSH-Px) levels in Group 2 were lower than those in Group 1 (P < 0.05). The level of angiotensin II (AT-II) in group 1 was lower than that in group 2 (P < 0.001). Cardiac dysfunction secondary to myocardial infarction could induce cardiorenal interactions in SHRs. It could be interpreted by the activation of oxidative stress, changes in inflammation and alteration of renin–angiotensin–aldosterone system. [ABSTRACT FROM AUTHOR]

Background Heart failure with preserved ejection fraction (HFpEF) often coexists with chronic kidney disease (CKD). Exercise intolerance is a major determinant of quality of life and morbidity in both scenarios. We aimed to evaluate the associations between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and carbohydrate antigen 125 (CA125) with maximal aerobic capacity (peak VO2) in ambulatory HFpEF and whether these associations were influenced by kidney function. Methods This single-centre study prospectively enrolled 133 patients with HFpEF who performed maximal cardiopulmonary exercise testing. Patients were stratified across estimated glomerular filtration rate (eGFR) categories (<60 ml/min/1.73 m2 versus ≥60 ml/min/1.73 m2). Results The mean age of the sample was 73.2 ± 10.5 years and 56.4% were female. The median of peak VO2 was 11.0 ml/kg/min (interquartile range 9.0–13.0). A total of 67 (50.4%) patients had an eGFR <60 ml/min/1.73 m2. Those patients had higher levels of NT-proBNP and lower peak VO2, without differences in CA125. In the whole sample, NT-proBNP and CA125 were inversely correlated with peak VO2 (r  = −0.43, P  < .001 and r  = −0.22, P  = .010, respectively). After multivariate analysis, we found a differential association between NT-proBNP and peak VO2 across eGFR strata (P for interaction = .045). In patients with an eGFR ≥60 ml/min/1.73 m2, higher NT-proBNP identified patients with poorer maximal functional capacity. In individuals with eGFR <60 ml/min/1.73 m2, NT-proBNP was not significantly associated with peak VO2 [β = 0.02 (95% confidence interval −0.19–0.23), P  = .834]. Higher CA125 was linear and significantly associated with worse functional capacity without evidence of heterogeneity across eGFR strata (P for interaction = .620). Conclusions In patients with stable HFpEF, NT-proBNP was not associated with maximal functional capacity when CKD was present. CA125 emerged as a useful biomarker for estimating effort intolerance in HFpEF irrespective of the presence of CKD. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) can lead to cardiac dysfunction in a condition known as cardiorenal syndrome (CRS). It is postulated that the accumulation of uremic toxins in the bloodstream, as a consequence of declining kidney function, may contribute to these adverse cardiac effects. While CRS in adults has been extensively studied, there is a significant knowledge gap with pediatric patients. Uremic toxin levels in children remain inadequately characterized and quantified compared to adults. This review aims to systematically evaluate the association between uremic toxin concentrations and cardiac changes in pediatric CRS and to examine the impact of different dialysis modalities, specifically hemodialysis and peritoneal dialysis, on uremic toxin clearance and cardiovascular parameters. To address this, we conducted a systematic literature search of PubMed, following PRISMA guidelines. We used the terms "uremic toxins" and "cardiorenal syndrome" with variations in syntax to search for studies discussing the relationship between uremic toxin levels in CKD, the subsequent impact on cardiac parameters, and the emergence of cardiac dysfunction. Full-text articles written in English, conducted on humans aged from birth to 18 years, and published until December 2021 were included. A comprehensive literature search yielded six studies, and their risk of bias was assessed using JBI Critical Appraisal Checklists. Our systematic review is registered on PROSPERO, number CRD42023460072. This synthesis intends to provide an understanding of the role of uremic toxins in pediatric CRS. The findings reveal that pediatric patients with end-stage CKD on dialysis exhibit elevated uremic toxin levels, which are significantly associated with cardiovascular disease parameters. Additionally, the severity of CKD correlated with higher uremic toxin levels. No conclusive evidence was found to support the superiority of either hemodialysis or peritoneal dialysis in terms of uremic toxin clearance or cardiovascular outcomes. More pediatric-specific standardized and longitudinal studies are needed to develop targeted treatments and improve clinical outcomes and the quality of life for affected children. [ABSTRACT FROM AUTHOR]

The term "Cardiorenal Syndrome" (CRS) refers to the complex interplay between heart and kidney dysfunction. First described by Robert Bright in 1836, CRS was brought to its modern view by Ronco et al. in 2008, who defined it as one organ's primary dysfunction leading to secondary dysfunction in the other, a view that led to the distinction of five different types depending on the organ of primary dysfunction and the temporal pattern (acute vs. chronic). Their pathophysiology is intricate, involving various hemodynamic, neurohormonal, and inflammatory processes that result in damage to both organs. While traditional biomarkers have been utilized for diagnosing and prognosticating CRS, they are inadequate for the early detection of acute renal damage. Hence, there is a pressing need to discover new biomarkers to enhance clinical outcomes and treatment approaches. [ABSTRACT FROM AUTHOR]

Congestive nephropathy is an underappreciated manifestation of cardiorenal syndrome and is characterized by a potentially reversible kidney dysfunction caused by a reduced renal venous outflow secondary to right‐sided heart failure or intra‐abdominal hypertension. To date, the histological diagnostic criteria for congestive nephropathy have not been defined. We herein report a case of acute renal dysfunction following cardiac allograft failure and present a review of the relevant literature to elucidate the current understanding of the disease. Our case demonstrated that congestion‐driven nephropathy may be histopathologically characterized by markedly dilated veins and peritubular capillaries, focally accentuated low‐grade acute tubular damage, small areas of interstitial fibrosis, and tubular atrophy on a background of normal glomeruli and predominantly normal tubular cell differentiation. [ABSTRACT FROM AUTHOR]

Aims: Fractional excretion of urea nitrogen (FEUN), used to differentiate the cause of acute kidney injury, has emerged as a useful fluid index in patients with heart failure (HF). We hypothesized that FEUN could be useful in identifying worsening renal function (WRF) associated with poor outcomes in patients with acute HF (AHF). Methods and results: Overall, 1103 patients with AHF (median age, 78 years; male proportion, 60%) were categorized into six groups according to the presence of WRF and FEUN values (low, ≤32.1%; medium, >32.1% and ≤38.0%; and high, >38.0%) at discharge. WRF was defined as an increase of ≥0.3 mg/dL in the serum creatinine level from admission to discharge. FEUN was calculated by the following formula: (urinary urea × serum creatinine) × 100/(serum urea × urinary creatinine). The cut‐off values for low, medium, and high FEUN were based on a previous study. The primary outcome of this study was HF readmission after hospital discharge. During the 1 year follow‐up, 170 HF readmissions occurred. Kaplan–Meier analysis revealed significantly higher HF readmission rates in patients with WRF than in those without WRF (log‐rank test, P < 0.001). Additionally, among patients with WRF, HF readmission rates were lowest in those with medium FEUN values, followed by those with low FEUN values and those with high FEUN values. On multivariable analysis, the presence of WRF with low or high FEUN values was independently associated with increased HF readmission, as compared with the absence of WRF with medium FEUN values. Notably, no association was noted between WRF with medium FEUN values and HF readmission. Conclusions: The prognostic impact of WRF was significantly mediated by the FEUN values and was associated with worse outcomes only when the FEUN values were either low or high. Our study suggests that FEUN can identify prognostically relevant WRF in patients with AHF. [ABSTRACT FROM AUTHOR]

Background Continuous ultrafiltration consists a decongestion method for patients with refractory decompensated heart failure with diuretic resistance as it enables the energetic withdrawal of isotonic fluid under controlled rate according to the patient's vital signs, offering decongestion without exceeding plasma refill rate. Case summary A 62-year-old male with history of Holt–Oram syndrome with Eisenmenger physiology presented with worsening dyspnoea. Patient initial clinical and laboratory examination, renal vein ultrasound, and echocardiogram were consistent with significant congestion. A combined strategy of intravenous furosemide with early initiation of continuous ultrafiltration at an adjustable rate for 4 days was finally selected. Patient remained haemodynamically stable during the total treatment time and exhibited significant clinical and laboratory improvement. Consecutive renal vein ultrasounds and echocardiograms demonstrated a continuous and steady recession of congestion. During the 4 days of ultrafiltration, total fluid loss was estimated at 42 L. Patient remained asymptomatic without signs of worsened congestion at 1, 3, and 5 months follow-up. Discussion Our case depicts that continuous ultrafiltration without exceeding plasma refill rate allows an impaired right ventricle to maintain significant preload. This suggests that it might be considered for patients in whom a session of short classic ultrafiltration might have detrimental results regarding cardiac output. [ABSTRACT FROM AUTHOR]

Cardiorenal syndrome (CRS) is a life-threatening disorder that involves a complex interplay between the two organs. Managing this multifaceted syndrome is challenging in the hospital and requires a multidisciplinary approach to tackle the many manifestations and complications. There is no universally accepted algorithm to treat patients, and therapeutic options vary from one patient to another. The mainstays of therapy involve the stabilization of hemodynamics, decongestion using diuretics or renal replacement therapy, improvement of cardiac output with inotropes, and goal-directed medical treatment with renin–angiotensin–aldosterone system inhibitors, beta-blockers, and other medications. Mechanical circulatory support is another viable option in the armamentarium of agents that improve symptoms in select patients.

Abstract In rats with unilateral nephrectomy and cardiac dysfunction, renal function deteriorates at an accelerated rate, as evidenced by increased proteinuria. Whether myocardial infarct-induced heart failure (HF) exacerbates renal injury in hypertensive rats with mild renal injury has not been reported. Rats underwent either coronary ligation or sham surgery. Thirty spontaneously hypertensive rats (SHRs) aged 8 weeks were randomly divided into two groups. Group 1 was the sham group, in which the rats underwent thoracotomy without ligation of the coronary artery. Group 2 underwent coronary artery ligation. The rats in group 2 underwent coronary artery ligation on week 0. The experiment lasted 12 weeks. Urine was collected in metabolic cages over a 24-h period. Urine was collected from the rats 2 days before the end of the experiment, and the ratio of urinary protein to urinary creatinine was measured in the clinical laboratory. All rats were examined by echocardiogram one day before the end of the experiment. On the last day of the experiment, blood was collected and sent to the laboratory for analysis. Hematoxylin–eosin (HE) and periodic acid-Schiff (PAS) staining were performed on heart and kidney sections. The ejection fraction in group 2 was lower than that in group 1 (P

Abstract Aims Fractional excretion of urea nitrogen (FEUN), used to differentiate the cause of acute kidney injury, has emerged as a useful fluid index in patients with heart failure (HF). We hypothesized that FEUN could be useful in identifying worsening renal function (WRF) associated with poor outcomes in patients with acute HF (AHF). Methods and results Overall, 1103 patients with AHF (median age, 78 years; male proportion, 60%) were categorized into six groups according to the presence of WRF and FEUN values (low, ≤32.1%; medium, >32.1% and ≤38.0%; and high, >38.0%) at discharge. WRF was defined as an increase of ≥0.3 mg/dL in the serum creatinine level from admission to discharge. FEUN was calculated by the following formula: (urinary urea × serum creatinine) × 100/(serum urea × urinary creatinine). The cut‐off values for low, medium, and high FEUN were based on a previous study. The primary outcome of this study was HF readmission after hospital discharge. During the 1 year follow‐up, 170 HF readmissions occurred. Kaplan–Meier analysis revealed significantly higher HF readmission rates in patients with WRF than in those without WRF (log‐rank test, P

Abstract Congestive nephropathy is an underappreciated manifestation of cardiorenal syndrome and is characterized by a potentially reversible kidney dysfunction caused by a reduced renal venous outflow secondary to right‐sided heart failure or intra‐abdominal hypertension. To date, the histological diagnostic criteria for congestive nephropathy have not been defined. We herein report a case of acute renal dysfunction following cardiac allograft failure and present a review of the relevant literature to elucidate the current understanding of the disease. Our case demonstrated that congestion‐driven nephropathy may be histopathologically characterized by markedly dilated veins and peritubular capillaries, focally accentuated low‐grade acute tubular damage, small areas of interstitial fibrosis, and tubular atrophy on a background of normal glomeruli and predominantly normal tubular cell differentiation.

Abstract Background With the development of pathophysiology, cardiorenal syndrome (CRS), a complex and severe disease, has received increasing attention. Monocyte to high-density lipoprotein-cholesterol ratio (MHR) and body mass index (BMI) are independent risk factors for cardiovascular diseases, but their association with CRS remains unexplored. This study aims to explore the independent and joint effects of MHR and BMI on CRS. Methods We included 42,178 NHANES participants. The determination of CRS referred to the simultaneous presence of cardiovascular disease (identified through self-report) and chronic kidney disease (eGFR

Introduction: Cardiac implantable electrical devices are able to affect kidney function through hemodynamic improvements. The cardiac contractility modulation (CCM) is a device-based therapy option for patients with symptomatic chronic heart failure (HF) despite optimized medical treatment. The long-term cardiorenal interactions for CCM treated patients are yet to be described. Methods: CCM recipients (n = 187) from the Mannheim Cardiac Contractility Modulation Observational Study (MAINTAINED) were evaluated in the long-term (up to 60 months) for changes in serum creatinine, estimated glomerular filtration rate (eGFR), other surrogate markers of kidney function, and the chronic kidney disease (CKD) stage distribution. With regard to kidney function at baseline, the patients were furthermore grouped to either advanced CKD (aCKD, CKD stage ≥3, eGFR≤59 mL/min/1.73 m2, n = 107) or preserved kidney function and mild CKD (pCKD, CKD stages 1–2, eGFR≥60 mL/min/1.73 m2, n = 80). The groups were compared for differences regarding kidney function, New York Heart Association classification (NYHA), biventricular systolic function, HF hospitalizations and other parameters in the long-term (60 months). Results: CKD stage distribution remained stable during the entire follow-up (p = 0.65). An increase in serum creatinine (1.47 ± 1 vs. 1.6±1 mg/dL) with a corresponding decline of eGFR (58.2 ± 23.4 vs. 54.2 ± 24.4 mL/min/1.73 m2, both p < 0.05) were seen after 60 months but not before for the total cohort, which was only significant in pCKD patients in terms of group comparison. Mean survival (54.3 ± 1.3 vs. 55.3 ± 1.2 months, p = 0.53) was comparable in both groups. Improvements in NYHA (3.11 ± 0.46 vs. 2.94 ± 0.41–2.28 ± 0.8 vs. 1.94 ± 0.6) and LVEF (24.8 ± 7.1 vs. 22.9 ± 6.6–31.1 ± 11.4 vs. 35.5 ± 11.1%) were likewise similar after 60 months (both p < 0.05). The aCKD patients suffered from more HF hospitalizations and ventricular tachycardias during the entire follow-up period (both p < 0.05). Conclusions: The kidney function parameters and CKD stage distribution might remain stable in CCM treated HF patients in the long-term, who experience improvements in LVEF and functional status, regardless of their kidney function before. An impaired kidney function might be associated with further cardiovascular comorbidities and more advanced HF before CCM, and could be an additional risk factor of HF complications afterward. [ABSTRACT FROM AUTHOR]

Background/Objectives: Cardiorenal syndrome (CRS) is a disorder of the heart and kidneys, with one type of organ dysfunction affecting the other. The pathophysiology is complex, and its actual description has been questioned. We used clustering analysis to identify clinically relevant phenogroups among patients with CRS. Methods: Data for patients admitted from 1 January 2012 to 31 December 2012 were collected from the French national medico-administrative database. Patients with a diagnosis of heart failure and chronic kidney disease and at least 5 years of follow-up were included. Results: In total, 13,665 patients were included and four clusters were identified. Cluster 1 could be described as the vascular–diabetes cluster. It comprised 1930 patients (14.1%), among which 60% had diabetes, 94% had coronary artery disease (CAD), and 80% had peripheral artery disease (PAD). Cluster 2 could be described as the vascular cluster. It comprised 2487 patients (18.2%), among which 33% had diabetes, 85% had CAD, and 78% had PAD. Cluster 3 could be described as the metabolic cluster. It comprised 2163 patients (15.8%), among which 87% had diabetes, 67% dyslipidemia, and 62% obesity. Cluster 4 comprised 7085 patients (51.8%) and could be described as the low-vascular cluster. The vascular cluster was the only one associated with a higher risk of cardiovascular death (HR: 1.48 [1.32–1.66]). The metabolic cluster was associated with a higher risk of kidney replacement therapy (HR: 1.33 [1.17–1.51]). Conclusions: Our study supports a new classification of CRS based on the vascular aspect of pathophysiology differentiating microvascular or macrovascular lesions. These results could have an impact on patients' medical treatment. [ABSTRACT FROM AUTHOR]

In recent decades, there has been considerable effort in investigating the clinical utility of renal Doppler measurements in both cardiovascular and renal disorders. In particular, a measure of renal arterial resistance, the renal resistive index (RRI), has been demonstrated to predict chronic kidney disease progression and acute kidney injury in different clinical settings. Furthermore, it is linked to a poorer prognosis in individuals suffering from chronic heart failure. Examining the renal venous flow through pulsed Doppler can offer additional insights into renal congestion and cardiovascular outcomes for these patients. This review seeks to summarize the existing data concerning the clinical significance of arterial and venous renal Doppler measurements across various cardiovascular and renal disease contexts. [ABSTRACT FROM AUTHOR]

Background: With the development of pathophysiology, cardiorenal syndrome (CRS), a complex and severe disease, has received increasing attention. Monocyte to high-density lipoprotein-cholesterol ratio (MHR) and body mass index (BMI) are independent risk factors for cardiovascular diseases, but their association with CRS remains unexplored. This study aims to explore the independent and joint effects of MHR and BMI on CRS. Methods: We included 42,178 NHANES participants. The determination of CRS referred to the simultaneous presence of cardiovascular disease (identified through self-report) and chronic kidney disease (eGFR < 60 mL/min per 1.73 m²). We employed multivariate weighted logistic regression to evaluate the odds ratio (OR) and 95% confidence interval (CI) for the independent and joint associations of MHR and BMI with CRS. We also conducted restricted cubic spines to explore nonlinear associations. Results: The prevalence of CRS was 3.45% among all participants. An increase in both MHR and BMI is associated with a higher risk of CRS (MHR: OR = 1.799, 95% CI = 1.520–2.129, P < 0.001, P-trend < 0.001; BMI: OR = 1.037, 95% CI = 1.023–1.051, P < 0.001). Individuals who simultaneously fall into the highest quartile of MHR and have a BMI of 30 or more face the highest risk of CRS compared to those in the lowest MHR quartile with a BMI of less than 25 (OR = 3.45, 95% CI = 2.40–4.98, P < 0.001). However, there is no interactive association between MHR and BMI with CRS. Conclusions: Higher MHR and BMI are associated with higher odds of CRS. MHR and BMI can serve as tools for early prevention and intervention of CRS, respectively. [ABSTRACT FROM AUTHOR]

Aims: Loop diuretics may exacerbate cardiorenal syndrome (CRS) in heart failure (HF). Direct sodium removal (DSR) using the peritoneal membrane, in conjunction with complete diuretic withdrawal, may improve CRS and diuretic resistance. Methods and results: Patients with HF requiring high‐dose loop diuretics were enrolled in two prospective, single‐arm studies: RED DESERT (n = 8 euvolaemic patients), and SAHARA (n = 10 hypervolaemic patients). Loop diuretics were withdrawn, and serial DSR was utilized to achieve and maintain euvolaemia. At baseline, participants required a median 240 mg (interquartile range [IQR] 200–400) oral furosemide equivalents/day, which was withdrawn in all participants during DSR (median time of DSR 4 weeks [IQR 4–6]). Diuretic response (queried by formal 40 mg intravenous furosemide challenge and 6 h urine sodium quantification) increased substantially from baseline (81 ± 37 mmol) to end of DSR (223 ± 71 mmol, p < 0.001). Median time to re‐initiate diuretics was 87 days, and the median re‐initiation dose was 8% (IQR 6–10%) of baseline. At 1 year, diuretic dose remained substantially below baseline (30 [IQR 7.5–40] mg furosemide equivalents/day). Multiple dimensions of kidney function such as filtration, uraemic toxin excretion, kidney injury, and electrolyte handling improved (p < 0.05 for all). HF‐related biomarkers including N‐terminal pro‐B‐type natriuretic peptide, carbohydrate antigen‐125, soluble ST2, interleukin‐6, and growth differentiation factor‐15 (p < 0.003 for all) also improved. Conclusions: In patients with HF and diuretic resistance, serial DSR therapy with loop diuretic withdrawal was feasible and associated with substantial and persistent improvement in diuretic resistance and several cardiorenal parameters. If replicated in randomized controlled studies, DSR may represent a novel therapy for diuretic resistance and CRS. Clinical Trial Registration: RED DESERT (NCT04116034), SAHARA (NCT04882358). [ABSTRACT FROM AUTHOR]

Background: In this investigation, we explored the effects of pharmacological cholinergic stimulation on cardiac function and renal inflammation following acute myocardial infarction (AMI) in spontaneously hypertensive rats (SHRs). Methods: Adult male SHRs were randomized into three experimental groups: sham-operated; AMI + Veh (infarcted, treated with vehicle); and AMI + PY (infarcted, treated with the cholinesterase inhibitor, pyridostigmine bromide (PY)—40 mg/kg, once daily for seven days). Rats were euthanized 7 or 30 days post-surgery. The clinical parameters were assessed on the day before euthanasia. Subsequent to euthanasia, blood samples were collected and renal tissues were harvested for histological and gene expression analyses aimed to evaluate inflammation and injury. Results: Seven days post-surgery, the AMI + PY group demonstrated improvements in left ventricular diastolic function and autonomic regulation, and a reduction in renal macrophage infiltration compared to the AMI + Veh group. Furthermore, there was a notable downregulation in pro-inflammatory gene expression and an upregulation in anti-inflammatory gene expression. Analysis 30 days post-surgery showed that PY treatment had a sustained positive effect on renal gene expression, correlated with a decrease in biomarkers, indicative of subclinical kidney injury. Conclusions: Short-term cholinergic stimulation with PY provides both cardiac and renal protection by mitigating the inflammatory response after AMI. [ABSTRACT FROM AUTHOR]

Background: Empagliflozin (EMPA) demonstrates cardioprotective effects on the patients with heart failure, but its effects in cardiorenal syndrome (CRS) remain unspecified. The purpose of the exploratory study was to investigate the effect of EMPA on patients with type 2 CRS and type 2 diabetes mellitus (DM). Methods: This study was a randomized trial of patients with type 2 CRS and DM done between December 2020 and January 2022. Patients were randomly allocated to the control group and the EMPA group using EMPA as an add-on treatment. Serum interleukin 6 (IL-6), janus kinase 2 (JAK-2), and signal transducer and activator of transcription 3 (STAT-3) concentrations were measured in 102 patients with CRS and healthy individuals without any disease using enzyme-linked immunosorbent assay before and after treatment. The evaluation of renal function was measured by immunoturbidimetry, and cardiac function was estimated by doppler echocardiography. Rates of adverse events and major adverse cardiac events (MACE) were documented. Results: The results showed that EMPA decreased the level of IL-6 but increased the level of JAK-2 and STAT-3 in patients. Additionally, the results suggest EMPA significantly reduced the incidence of MACE compared to the control group, while the rate of adverse events did not significantly differed. Conclusions: Our study suggested that the cardiorenal benefits conferred by EMPA might be driven by anti-inflammatory effects, cooperated with the activation of JAK2/STAT3 signaling pathways, leading to modest short-term improvements in patients with type 2 CRS. The overall safety and low complication make EMPA a significant choice for clinical application. [ABSTRACT FROM AUTHOR]

Acute kidney injury represents a significant threat in cardiac surgery regarding complications and costs. Novel preventive approaches are needed, as the therapeutic modalities are still limited. As experimental studies have demonstrated, glutamine, a conditionally essential amino acid, might have a protective role in this setting. Moreover, the levels of glutamine after the cardiopulmonary bypass are significantly lower. In clinical practice, various trials have investigated the effects of glutamine supplementation on cardiac surgery with encouraging results. However, these studies are heterogeneous regarding the selection criteria, timing, dose, outcomes studied, and way of glutamine administration. This narrative review aims to present the potential role of glutamine in cardiac surgery-associated acute kidney injury prevention, starting from the experimental studies and guidelines to the clinical practice and future directions. [ABSTRACT FROM AUTHOR]

Introduction and aim. Systemic lupus erythematosus (SLE) is a chronic, autoimmune disorder that may affect every organ. The use of immunosuppression has changed a natural course of the disease. Thereupon mortality in SLE is not only associated with implications of disease activity and its impact on cardiovascular system but also with treatment-related complications like cytopenia or increased risk of infection, which can lead to a life-threatening sepsis. Description of the case. We present a case of a 60-year-old Caucasian female patient with a long-time history of active SLE, who has first developed nephrotic syndrome and then acute lupus myocarditis (LM) complicated by dilated cardiomyopathy. Conclusion: The appearance of LM and its complications seem to be a landmark event in the further course of disease.

Background: Cardiorenal syndrome (CRS) is a complex condition characterized by the interplay of immune imbalance and inflammation. The C-reactive protein-Albumin-lymphocyte (CALLY) CALLY index serves as a new immune-nutritional scoring system, but its predictive value for CRS remains to be established. Methods: In this study, we analyzed data from 27,978 participants in National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010. The CALLY index was calculated as the ratio of albumin to lymphocyte, divided by C-reactive protein (CRP) multiplied by 104. CRS was defined by the coexistence of cardiovascular disease and chronic kidney disease (eGFR

AimsKidney function changes dynamically during AHF treatment, but risk factors for and consequences of worsening renal function (WRF) at hospital admission are uncertain. We aimed to determine the significance of WRF at admission for acute heart failure (AHF).Methods and resultsWe evaluated a subgroup of 406 patients from The Acute Kidney Injury Neutrophil gelatinase-associated lipocalin Evaluation of Symptomatic heart failure Study (AKINESIS) who had serum creatinine measurements available within 3 months before and at the time of admission. Admission WRF was primarily defined as a 0.3 mg/dL or 50% creatinine increase from preadmission. Alternative definitions evaluated were a ≥0.5 mg/dL creatinine increase, ≥25% glomerular filtration rate decrease, and an overall change in creatinine. Predictors of admission WRF were evaluated. Outcomes evaluated were length of hospitalization, a composite of adverse in-hospital events, and the composite of death or HF readmission at 30, 90, and 365 days. Biomarkers' prognostic ability for these outcomes were evaluated in patients with admission WRF. One-hundred six patients (26%) had admission WRF. These patients had features of more severe AHF with lower blood pressure, higher BUN, and lower serum sodium concentrations at admission. Higher BNP (odds ratio [OR] per doubling 1.16-1.28, 95% confidence interval [CI] 1.00-1.55) and lower diastolic blood pressure (OR 0.97-0.98, 95% CI 0.96-0.99) were associated with a higher odds for the three definitions of admission WRF. The primary WRF definition was not associated with a longer hospitalization, but alternative WRF definitions were (1.3 to 1.6 days longer, 95% CI 1.0-2.2). WRF across definitions was not associated with a higher odds of adverse in-hospital events or a higher risk of death or HF readmission. In the subset of patients with WRF, biomarkers were not prognostic for any outcome.ConclusionsAdmission WRF is common in AHF patients and is associated with an increased length of hospitalization, but not adverse in-hospital events, death, or HF readmission. Among those with admission WRF, biomarkers did not risk stratify for adverse events.

Background. The pandemic of noncommunicable chronic diseases and the high prevalence of combined damage to the cardiovascular system and kidneys determine the relevance of continuing scientific research to solve these medical problems. Therefore, the aim of this study was to compare the influence of the Earth’s electromagnetic field on the occurrence of episodes of kidney disease and myocardial infarction in order to search for new pathogenetic components of cardiorenal syndrome and deepen fundamental knowledge. According to the Lithuanian magnetometer GCI003, a number of stu­dies in 2014–2018 found that changes in the Earth’s electromagnetic field may play an important role in the pathogenesis of cardiovascular diseases as well as their incidence. Since the functioning of the cardiovascular system and kidneys are closely connected through the metabolic processes of the cardiorenal metabolic axis, this study tested the hypothesis that changes in the Earth’s electromagnetic field may also affect the pathogenesis of kidney disease as the changes of local magnetic field have been shown to influence the functioning of the cardiovascular system. Materials and methods. This was a search retrospective study on the relationship between the influence of local Schumann resonances and the occurrence of hospitalizations in 1340 patients with kidney disease. It also examined the relationship between local Schumann resonances and heart attacks in patients admitted to the University Hospital of the Lithuanian University of Health Sciences (703 patients). Mean power of local magnetic field fluctuations in Lithuania was measured in pT2 s2 in five different frequency ranges, which overlaps the Schumann resonance and electroencephalogram’s frequency ranges: SDelta (0–3.5 Hz), STheta (3.5–7 Hz), SAlpha (7–15 Hz), SBeta (15–32 Hz), SGamma (32–66 Hz). The data of hospitalizations to the Nephrology Department of University Hospital and the dynamics of Schumann resonances were analyzed from January 1, 2021 to December 31, 2021. The data of hospitalizations for myocardial infarction to the Cardiology Department of University Hospital and the dynamics of Schumann resonances were studied from January 1, 2016 to December 31, 2016. Results. It was found that changes in the strength of the Earth’s local magnetic field in 2016 and 2021 were comparable and corresponded to the characteristic annual dynamics of the Earth’s local electromagnetic fields. This made it possible to conduct a comparative analysis of annual correlation graphs and establish general trends in the dynamics of indicators and graphical similarities. It confirmed the pre­sence of a general dependence of reactions to the external electromagnetic field of the Earth in female and male patients both with nephrological pathology and myocardial infarction. In nephrological patients of both sexes, all correlation coefficients in all ranges of Schumann resonances were positive. The only negative correlation coefficient P5 (SGamma) [32; 65] Hz (r = –0.069; p = 0.313) was in the female group. This fact as well as the presence of a significant dynamics of the correlation coefficient P5 (SGamma) [32; 65] Hz (r = 0.009; p = 0.475) in the male group indicate that higher magnetic field strength in this frequency range may be associated with a reduced incidence of kidney disease. We obtained data that a higher magnetic field intensity in the gamma range from 32 to 65 Hz as a pathogenetic component can contribute to the destabilization of the cardiovascular system, but at the same time it is associated with a positive effect on the state of nephrological pathology. Based on this, we can tentatively assume the opposite direction of the Earth’s electromagnetic field influence on the pathogenetic mechanisms of renal and cardiovascular diseases. This is clearly demonstrated by comparing the correlation coefficients between the incidence of kidney disease and the occurrence of myocardial infarction in men and women. The Earth’s stronger magnetic field in the gamma range contributes to an increase in the incidence of myocardial infarction, which is confirmed by the large number of patients during this period. Under these same conditions, a decrease in the incidence of kidney disease has been detected. This opposite direction is observed in both sexes. But in women the reaction is stronger, which is confirmed by a larger difference in correlation coefficients. Conclusions. 1. Changes in the Earth’s electromagnetic field are related to the functional state of the cardiovascular system and the condition of the kidneys. 2. It can be assumed that the effect of the Earth’s electromagnetic field on the pathogenetic mechanisms of kidney disease is in the opposite direction of that on the cardiovascular one. 3. Reliable gender differences in correlations between the influence of changes in the local Schumann resonance on the functional state of the cardiovascular system and kidneys were not found. 4. The connection of the Earth’s local geomagnetic field with kidney function may be another new unexplored pathogenetic mechanism in cardiorenal syndrome and noncommunicable chronic diseases.

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

Sodium is the main osmotically active ion in the extracellular fluid and its concentration goes hand in hand with fluid volume. Under physiological conditions, homeostasis of sodium and thus amount of fluid is regulated by neural and humoral interconnection of body tissues and organs. Both heart and kidneys are crucial in maintaining volume status. Proper kidney function is necessary to excrete regulated amount of water and solutes and adequate heart function is inevitable to sustain renal perfusion pressure, oxygen supply etc. As these organs are bidirectionally interconnected, injury of one leads to dysfunction of another. This condition is known as cardiorenal syndrome. It is divided into five subtypes regarding timeframe and pathophysiology of the onset. Hemodynamic effects include congestion, decreased cardiac output, but also production of natriuretic peptides. Renal congestion and hypoperfusion leads to kidney injury and maladaptive activation of renin-angiotensin-aldosterone system and sympathetic nervous system. In cardiorenal syndromes sodium and water excretion is impaired leading to volume overload and far-reaching negative consequences, including higher morbidity and mortality of these patients. [ABSTRACT FROM AUTHOR]

Background: Inflammation is essential in cardiorenal syndrome, however there is still a lack of evidence proving the interaction between cardiac injury, renal dysfunction and the inflammatory response. This study aimed to illustrate the association between renal dysfunction and cardiac injury with a specific focus on the role of inflammation. Methods: A single-center, retrospective study included patients with heart failure admitted to the cardiovascular department from September 2019 to April 2022. Patients received cardiovascular magnetic resonance (CMR) imaging (T1 mapping and late gadolinium enhancement (LGE)). Demographic, creatinine and native T1 were analyzed using pearson correlation, linear regression and adjusted for confounders. Interaction and subgroup analysis were performed. Results: Finally, 50 validated heart failure (HF) patients (age 58.5 ± 14.8 years; 78.0% men) were included. Cardiac global native T1 for the high estimated glomeruar filtration rate (eGFR) group was 1117.0 ± 56.6 ms, and for the low eGFR group was 1096.5 ± 61.8 ms. Univariate analysis identified global native T1 (β = 0.16, 95% confidence interval (CI): 0.04-0.28, p = 0.014) and C-reactive protein (CRP) (β = 0.30, 95% CI: 0.15-0.45, p < 0.001) as determinants of creatinine. Multivariable linear regression analysis identified global native T1 (β = 0.12, 95% CI: 0.01-0.123, p = 0.040) as a determinant of creatinine while age and diabetes were adjusted. Significant interactions between CRP and global native T1 in relation to creatinine level (p for interaction = 0.005) were identified. Conclusions: Kidney dysfunction was associated with cardiac injury and inflammation, respectively. The interaction between myocardial injury and kidney dysfunction is contingent on the severity of the inflammatory response. Further studies were needed to identify the mechanisms of the inflammatory response in cardiorenal syndrome. [ABSTRACT FROM AUTHOR]

Cardiorenal syndrome (CRS) involves joint dysfunction of the heart and kidney. Acute forms share biochemical alterations like hyperuricaemia (HU) with tumour lysis syndrome (TLS). The mainstay treatment of acute CRS with systemic overload is diuretics, but rasburicase is used in TLS to prevent and treat hyperuricaemia. An observational, retrospective study was performed to assess the effectiveness and safety of a single dose of rasburicase in hospitalized patients with cardiorenal syndrome, worsening renal function and uric acid levels above 9 mg/dL. Rasburicase improved diuresis and systemic congestion in the 35 patients included. A total of 86% of patients did not need to undergo RRT, and early withdrawal was possible in the remaining five. Creatinine (Cr) decreased after treatment with rasburicase from a peak of 3.6 ± 1.27 to 1.79 ± 0.83 mg/dL, and the estimated glomerular filtration rate (eGFR) improved from 17 ± 8 to 41 ± 20 mL/min/1.73 m2 (p = 0.0001). The levels of N-terminal type B Brain Natriuretic Peptide (Nt-ProBNP) and C-reactive protein (CRP) were also significantly reduced. No relevant adverse events were detected. Our results show that early treatment with a dose of rasburicase in patients with CRS and severe HU is effective to improve renal function and systemic congestion, avoiding the need for sustained extrarenal clearance, regardless of comorbidities and ventricular function. [ABSTRACT FROM AUTHOR]

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

Chronic kidney disease (CKD) affects > 10% of the global adult population and significantly increases the risk of cardiovascular disease (CVD), which remains the leading cause of death in this population. The development and progression of CVD—compared to the general population—is premature and accelerated, manifesting as coronary artery disease, heart failure, arrhythmias, and sudden cardiac death. CKD and CV disease combine to cause multimorbid cardiorenal syndrome (CRS) due to contributions from shared risk factors, including systolic hypertension, diabetes mellitus, obesity, and dyslipidemia. Additional neurohormonal activation, innate immunity, and inflammation contribute to progressive cardiac and renal deterioration, reflecting the strong bidirectional interaction between these organ systems. A shared molecular pathophysiology—including inflammation, oxidative stress, senescence, and hemodynamic fluctuations characterise all types of CRS. This review highlights the evolving paradigm and recent advances in our understanding of the molecular biology of CRS, outlining the potential for disease-specific therapies and biomarker disease detection. [ABSTRACT FROM AUTHOR]

Chronic Cardiovascular and Kidney Disorder (CCKD) represents a growing challenge in healthcare, characterized by the complex interplay between heart and kidney diseases. This manuscript delves into the "butterfly effect" in CCKD, a phenomenon in which acute injuries in one organ lead to progressive dysfunction in the other. Through extensive review, we explore the pathophysiology underlying this effect, emphasizing the roles of acute kidney injury (AKI) and heart failure (HF) in exacerbating each other. We highlight emerging therapies, such as renin–angiotensin–aldosterone system (RAAS) inhibitors, SGLT2 inhibitors, and GLP1 agonists, that show promise in mitigating the progression of CCKD. Additionally, we discuss novel therapeutic targets, including Galectin-3 inhibition and IL33/ST2 pathway modulation, and their potential in altering the course of CCKD. Our comprehensive analysis underscores the importance of recognizing and treating the intertwined nature of cardiac and renal dysfunctions, paving the way for more effective management strategies for this multifaceted syndrome. [ABSTRACT FROM AUTHOR]

Background The mineralocorticoid receptor plays a significant role in the development of chronic kidney disease (CKD) and associated cardiovascular complications. Classic steroidal mineralocorticoid receptor antagonists are a therapeutic option, but their use in the clinic is limited due to the associated risk of hyperkalemia in patients with CKD. Finerenone is a nonsteroidal mineralocorticoid receptor antagonist that has been recently investigated in 2 large phase III clinical trials (FIDELIO‐DKD [Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease] and FIGARO‐DKD [Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease]), showing reductions in kidney and cardiovascular outcomes. Methods and Results We tested whether finerenone improves renal and cardiac function in a preclinical nondiabetic CKD model. Twelve weeks after 5/6 nephrectomy, the rats showed classic signs of CKD characterized by a reduced glomerular filtration rate and increased kidney weight, associated with left ventricular (LV) diastolic dysfunction and decreased LV perfusion. These changes were associated with increased cardiac fibrosis and reduced endothelial nitric oxide synthase activating phosphorylation (ser 1177). Treatment with finerenone prevented LV diastolic dysfunction and increased LV tissue perfusion associated with a reduction in cardiac fibrosis and increased endothelial nitric oxide synthase phosphorylation. Curative treatment with finerenone improves nondiabetic CKD‐related LV diastolic function associated with a reduction in cardiac fibrosis and increased cardiac phosphorylated endothelial nitric oxide synthase independently from changes in kidney function. Short‐term finerenone treatment decreased LV end‐diastolic pressure volume relationship and increased phosphorylated endothelial nitric oxide synthase and nitric oxide synthase activity. Conclusions We showed that the nonsteroidal mineralocorticoid receptor antagonist finerenone reduces renal hypertrophy and albuminuria, attenuates cardiac diastolic dysfunction and cardiac fibrosis, and improves cardiac perfusion in a preclinical nondiabetic CKD model.

A 54-year-old woman with a diagnosis of Erdheim-Chester disease under therapy with dabrafenib presents with clinical signs of heart failure. After discontinuing the offending medication and initiating guideline-directed medical therapy for heart failure with reduced ejection fraction, the clinical picture improved.

As early as the first stages of rheumatic diseases in children, a number of pathological changes occur with the involvement of many organs and systems in the process. In children with juvenile idiopathic arthritis (JIA), decreased adaptability of the cardiovascular system is detected in 17.0–20.0 % of cases. 36.9 % of children with JIA develop renal lesions. Thus, inflammation underlies the interaction between pathological mechanisms of renal and heart failure in patients with rheumatic diseases. The aim of the work is to identify the characteristics of the interaction between main morphofunctional parameters of the cardiovascular system and kidneys in children with JIA, and the factors that give rise to the formation and worsening of these disorders. Materials and methods. 152 patients aged 13.42 ± 0.22 years with JIA were examined. Renal functions were examined based on the levels of creatinine, urea, albuminuria, urine specific gravity, glomerular filtration rate. To determine the morphofunctional parameters of the heart, ultrasound examinations of both left and right ventricles were performed. Results. In children with JIA, the functional parameters of the kidneys almost do not differ from those of the control group, with the exception of albuminuria, which is significantly higher in children of the main group and increases with the process activity progression. Morphofunctional analysis of the cardiac parameters has shown a decrease in the stroke volume of the left ventricle (51.83 ± 1.57 ml against 57.86 ± 2.54 ml, р < 0.05) with preserved ejection fraction and a significant increase in the right ventricle volumes both diastolic (34.54 ± 1.51 ml against 22.45 ± 2.11 ml, p < 0.001) and systolic (19.15 ± 0.96 ml against 10.18 ± 1.14 ml, p < 0.001), as well as stroke volume (15.39 ± 0.84 ml against 12.21 ± 1.05 ml, p < 0.01), with a significant decrease in its ejection fraction (45.04 ± 1.44 % against 56.06 ± 1.59 %, p < 0.001). Conclusions. Renal functional parameters are within normal values, but the level of albuminuria is significantly higher and increases with the process activity progression in children with JIA. The morphofunctional parameters of the left ventricle correspond to the control ones, but there is an increase in the right ventricle volume with a significant decrease in its ejection fraction. A decrease in the myocardial pumping function of the right ventricle is accompanied by a decrease in renal blood supply which leads to the development of cardiorenal syndrome type 5 in JIA children.

Introduction: Apela has a wide range of biological effects on the cardiovascular system, but the changes and significance of endogenous Apela in patients with chronic heart failure (CHF) and acute deterioration of cardiac and renal function are unclear. Methods: A total of 69 patients with stable CHF combined with well-preserved renal function were enrolled and followed for 12 months. The effects of Apela on human renal glomerular endothelial cells (hRGEC), human glomerular mesangial cells (hMC), and human renal tubular epithelial cells (HK-2) were observed. Results: Serum Apela concentration was positively correlated with NYHA class (r = 0.711) and N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration (r = 0.303) but negatively correlated with left ventricular ejection fraction (LVEF) (r = −0.374) and 6-min walk distance (r = −0.860) in patients with stable CHF. Twenty-one patients experiencing deterioration of renal and cardiac function were diagnosed with cardiorenal syndrome (CRS) during the follow-up period. In addition, the serum Apela, as well as the difference in Apela between stable and worsening phases (ΔApela), was correlated with the estimated glomerular filtration rate (eGFR) and ΔeGFR in patients with CRS. Apela significantly inhibited the upregulated expression of MCP-1 and TNF-α induced by angiotensin II (AngII) in hRGEC, hMC, and HK-2 cells. Apela inhibited the adhesion of THP-1 cells to hRGEC and promoted the tubular formation of hRGEC. Moreover, Apela enhanced the expression of MMP-9 in hMC but inhibited the upregulated expression of α-SMA and vimentin in HK-2 cells by AngII. Conclusion: This study suggests that the level of Apela can be used to diagnose heart failure and assess the severity of cardiac dysfunction in patients with stable CHF, and its dynamic changes can be used to evaluate the damage to renal function in patients with CRS. Apela plays multiple protective effects on renal cells, highlighting its clinical application prospect in the prevention and treatment of CRS.

Penyakit ginjal dan jantung merupakan penyakit yang memiliki tingkat morbiditas dan mortalitas yang tinggi. Organ ginjal dan jantung memiliki faktor risiko vaskular yang sama dan saling terkait. Disfungsi pada satu organ tersebut akan mempengaruhi satu organ lainnya. Hubungan permasalahan dua organ disebut dengan Cardiorenal Syndrome (CRS). Penanganan intervensi kombinasi ginjal dan jantung membutuhkan analisis yang dalam. Studi kasus ini bertujuan untuk menganalisis kasus Chronic Kidney Disease (CKD) pada pasien dengan Cardiorenal Syndrome (CRS) di ruang Intensif Care Unit (ICU). Studi kasus ini menggunakan metode case report dengan single case yang dilakukan melalui rangkaian proses asuhan keperawatan berupa pengkajian, perumusan masalah keperawatan, intervensi, implementasi, dan evaluasi keperawatan. Studi kasus ini dilakukan dengan cara memberikan asuhan keperawatan pada pasien CKD di ruang ICU selama 5 hari. Masalah keperawatan utama pada pasien Cardiorenal Syndrome yaitu penurunan curah jantung berhubungan dengan preload dan kontraktilitas. Hasil evaluasi asuhan keperawatan selama 5 hari menunjukkan hemodinamika membaik, nadi perifer teraba agak kuat, takikardia menurun, edema menurun dari derajat 2 menjadi derajat 1, hemoglobin membaik, belum ada hasil pemeriksaan TTE (Transthoracic echocardiography) ulang, dan kesadaran pasien masih soporcoma E2M2Vett. Proses keperawatan yang tepat dapat berkontribusi terhadap perbaikan hemodinamika, penurunan derajat edema, serta perbaikan hemoglobin pasien Chronic Kidney Disease (CKD) dengan Cardiorenal Syndrome (CRS).

Abstract Background Heart failure (HF), chronic kidney disease (CKD), and type 2 diabetes mellitus (T2DM) are common and interrelated conditions, each with a significant burden of disease. HF and kidney disease progress through pathophysiologic pathways that culminate in end-stage disease, for which T2DM is a major risk factor. Intervention within these pathways can disrupt disease processes and improve patient outcomes. Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have been investigated in patient populations with combinations of T2DM, CKD, and/or HF. However, until recently, the effect of these agents in patients with HF with preserved ejection fraction (HFpEF) was not well studied. Main body The aim of this review is to summarize key information regarding the interaction between HFpEF, CKD, and T2DM and discuss the role of SGLT2 inhibition in the management of patients with comorbid HFpEF and CKD, with or without T2DM. Literature was retrieved using Boolean searches for English-language articles in PubMed and Google Scholar and included terms related to SGLT2is, HFpEF, T2DM, and CKD. The reference lists from retrieved articles were also considered. Conclusion SGLT2is are efficacious and safe in treating HFpEF in patients with comorbid CKD with and without T2DM. The totality of evidence from clinical trials data suggests there are benefits in using SGLT2is across the spectrum of left ventricular ejection fractions, but there may be a potential for different renal effects in the different ejection fraction groups. Further analysis of these clinical trials has highlighted the need to obtain more accurate phenotypes for patients with HF and CKD to better determine which patients might respond to guideline-directed medical therapies, including SGLT2is. Graphical Abstract CI confidence interval, EF ejection fraction, eGFR estimated glomerular filtration rate, HF heart failure, HHF hospitalization for HF, HR hazard ratio, LVEF left ventricular ejection fraction, SGLT2i sodium-glucose cotransporter-2 inhibitor, UACR urine albumin-creatinine ratio. a Mean value, unless otherwise stated, b SGLT2i vs. placebo, c Data reanalyzed using more conventional endpoints (≥ 50% sustained decrease in eGFR, and including renal death) (UACR at baseline not stated in trial reports)

Despite a large amount of research on synchronous and mutually induced kidney and heart damage, the basis of the disease is still not fully clarified. Healthy mitochondria are essential for normal kidney and heart function. Mitochondrial dysfunction occurs when the clearance or process of generation and fragmentation of mitochondria is disturbed. The kidney is the second organ after the heart in terms of the number of mitochondria. Kidney tubules are rich in mitochondria due to the high energy requirements for absorption of large amounts of ultrafiltrate and dissolved substances. The place of action of oxidative stress is the influence on the balance in the production and breakdown of the mitochondrial reactive oxygen species. A more precise determination of the place and role of key factors that play a role in the onset of the disease is necessary for understanding the nature of the onset of the disease and the creation of therapy in the future. This underscores the urgent need for further research. The narrative review integrates results found in previously performed studies that have evaluated oxidative stress participation in cardiorenal syndrome type 3.

Chronic kidney disease (CKD) can lead to cardiac dysfunction in a condition known as cardiorenal syndrome (CRS). It is postulated that the accumulation of uremic toxins in the bloodstream, as a consequence of declining kidney function, may contribute to these adverse cardiac effects. While CRS in adults has been extensively studied, there is a significant knowledge gap with pediatric patients. Uremic toxin levels in children remain inadequately characterized and quantified compared to adults. This review aims to systematically evaluate the association between uremic toxin concentrations and cardiac changes in pediatric CRS and to examine the impact of different dialysis modalities, specifically hemodialysis and peritoneal dialysis, on uremic toxin clearance and cardiovascular parameters. To address this, we conducted a systematic literature search of PubMed, following PRISMA guidelines. We used the terms “uremic toxins” and “cardiorenal syndrome” with variations in syntax to search for studies discussing the relationship between uremic toxin levels in CKD, the subsequent impact on cardiac parameters, and the emergence of cardiac dysfunction. Full-text articles written in English, conducted on humans aged from birth to 18 years, and published until December 2021 were included. A comprehensive literature search yielded six studies, and their risk of bias was assessed using JBI Critical Appraisal Checklists. Our systematic review is registered on PROSPERO, number CRD42023460072. This synthesis intends to provide an understanding of the role of uremic toxins in pediatric CRS. The findings reveal that pediatric patients with end-stage CKD on dialysis exhibit elevated uremic toxin levels, which are significantly associated with cardiovascular disease parameters. Additionally, the severity of CKD correlated with higher uremic toxin levels. No conclusive evidence was found to support the superiority of either hemodialysis or peritoneal dialysis in terms of uremic toxin clearance or cardiovascular outcomes. More pediatric-specific standardized and longitudinal studies are needed to develop targeted treatments and improve clinical outcomes and the quality of life for affected children.

Rationale & objectiveHeart failure treatment relies on loop diuretics to induce natriuresis and decongestion, but the therapy is often limited by diuretic resistance. We explored the association of renin-angiotensin-aldosterone system (RAAS) activation with diuretic response.Study designObservational cohort.Setting & populationEuvolemic ambulatory adults with chronic heart failure were administered torsemide in a monitored environment.PredictorsPlasma total renin, active renin, angiotensinogen, and aldosterone levels. Urine total renin and angiotensinogen levels.OutcomesSodium output per doubling of diuretic dose and fractional excretion of sodium per doubling of diuretic dose.Analytical approachRobust linear regression models estimated the associations of each RAAS intermediate with outcomes.ResultsThe analysis included 56 participants, and the median age was 65 years; 50% were women, and 41% were Black. The median home diuretic dose was 80-mg furosemide equivalents. In unadjusted and multivariable-adjusted models, higher levels of RAAS measures were generally associated with lower diuretic efficiency. Higher plasma total renin remained significantly associated with lower sodium output per doubling of diuretic dose (β = -0.41 [-0.76, -0.059] per SD change) with adjustment; higher plasma total and active renin were significantly associated with lower fractional excretion of sodium per doubling of diuretic dose (β = -0.48 [-0.83, -0.14] and β = -0.51 [-0.95, -0.08], respectively) in adjusted models. Stratification by RAAS inhibitor use did not substantially alter these associations.LimitationsSmall sample size; highly selected participants; associations may not be causal.ConclusionsAmong multiple measures of RAAS activation, higher plasma total and active renin levels were consistently associated with lower diuretic response. These findings highlight the potential drivers of diuretic resistance and underscore the need for high-quality trials of decongestive therapy enhanced by RAAS blockade.

Introduction: Apela has a wide range of biological effects on the cardiovascular system, but the changes and significance of endogenous Apela in patients with chronic heart failure (CHF) and acute deterioration of cardiac and renal function are unclear. Methods: A total of 69 patients with stable CHF combined with well-preserved renal function were enrolled and followed for 12 months. The effects of Apela on human renal glomerular endothelial cells (hRGEC), human glomerular mesangial cells (hMC), and human renal tubular epithelial cells (HK-2) were observed. Results: Serum Apela concentration was positively correlated with NYHA class (r = 0.711) and N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration (r = 0.303) but negatively correlated with left ventricular ejection fraction (LVEF) (r = −0.374) and 6-min walk distance (r = −0.860) in patients with stable CHF. Twenty-one patients experiencing deterioration of renal and cardiac function were diagnosed with cardiorenal syndrome (CRS) during the follow-up period. In addition, the serum Apela, as well as the difference in Apela between stable and worsening phases (ΔApela), was correlated with the estimated glomerular filtration rate (eGFR) and ΔeGFR in patients with CRS. Apela significantly inhibited the upregulated expression of MCP-1 and TNF-α induced by angiotensin II (AngII) in hRGEC, hMC, and HK-2 cells. Apela inhibited the adhesion of THP-1 cells to hRGEC and promoted the tubular formation of hRGEC. Moreover, Apela enhanced the expression of MMP-9 in hMC but inhibited the upregulated expression of α-SMA and vimentin in HK-2 cells by AngII. Conclusion: This study suggests that the level of Apela can be used to diagnose heart failure and assess the severity of cardiac dysfunction in patients with stable CHF, and its dynamic changes can be used to evaluate the damage to renal function in patients with CRS. Apela plays multiple protective effects on renal cells, highlighting its clinical application prospect in the prevention and treatment of CRS. [ABSTRACT FROM AUTHOR]

Background. The pandemic of noncommunicable chronic diseases and the high prevalence of combined damage to the cardiovascular system and kidneys determine the relevance of continuing scientific research to solve these medical problems. Therefore, the aim of this study was to compare the influence of the Earth’s electromagnetic field on the occurrence of episodes of kidney disease and myocardial infarction in order to search for new pathogenetic components of cardiorenal syndrome and deepen fundamental knowledge. According to the Lithuanian magnetometer GCI003, a number of studies in 2014–2018 found that changes in the Earth’s electromagnetic field may play an important role in the pathogenesis of cardiovascular diseases as well as their incidence. Since the functioning of the cardiovascular system and kidneys are closely connected through the metabolic processes of the cardiorenal metabolic axis, this study tested the hypothesis that changes in the Earth’s electromagnetic field may also affect the pathogenesis of kidney disease as the changes of local magnetic field have been shown to influence the functioning of the cardiovascular system. Materials and methods. This was a search retrospective study on the relationship between the influence of local Schumann resonances and the occurrence of hospitalizations in 1340 patients with kidney disease. It also examined the relationship between local Schumann resonances and heart attacks in patients admitted to the University Hospital of the Lithuanian University of Health Sciences (703 patients). Mean power of local magnetic field fluctuations in Lithuania was measured in pT2 s2 in five different frequency ranges, which overlaps the Schumann resonance and electroencephalogram’s frequency ranges: SDelta (0–3.5 Hz), STheta (3.5–7 Hz), SAlpha (7–15 Hz), SBeta (15–32 Hz), SGamma (32–66 Hz). The data of hospitalizations to the Nephrology Department of University Hospital and the dynamics of Schumann resonances were analyzed from January 1, 2021 to December 31, 2021. The data of hospitalizations for myocardial infarction to the Cardiology Department of University Hospital and the dynamics of Schumann resonances were studied from January 1, 2016 to December 31, 2016. Results. It was found that changes in the strength of the Earth’s local magnetic field in 2016 and 2021 were comparable and corresponded to the characteristic annual dynamics of the Earth’s local electromagnetic fields. This made it possible to conduct a comparative analysis of annual correlation graphs and establish general trends in the dynamics of indicators and graphical similarities. It confirmed the presence of a general dependence of reactions to the external electromagnetic field of the Earth in female and male patients both with nephrological pathology and myocardial infarction. In nephrological patients of both sexes, all correlation coefficients in all ranges of Schumann resonances were positive. The only negative correlation coefficient P5 (SGamma) [32; 65] Hz (r = –0.069; p = 0.313) was in the female group. This fact as well as the presence of a significant dynamics of the correlation coefficient P5 (SGamma) [32; 65] Hz (r = 0.009; p = 0.475) in the male group indicate that higher magnetic field strength in this frequency range may be associated with a reduced incidence of kidney disease. We obtained data that a higher magnetic field intensity in the gamma range from 32 to 65 Hz as a pathogenetic component can contribute to the destabilization of the cardiovascular system, but at the same time it is associated with a positive effect on the state of nephrological pathology. Based on this, we can tentatively assume the opposite direction of the Earth’s electromagnetic field influence on the pathogenetic mechanisms of renal and cardiovascular diseases. This is clearly demonstrated by comparing the correlation coefficients between the incidence of kidney disease and the occurrence of myocardial infarction in men and women. The Earth’s stronger magnetic field in the gamma range contributes to an increase in the incidence of myocardial infarction, which is confirmed by the large number of patients during this period. Under these same conditions, a decrease in the incidence of kidney disease has been detected. This opposite direction is observed in both sexes. But in women the reaction is stronger, which is confirmed by a larger difference in correlation coefficients. Conclusions. 1. Changes in the Earth’s electromagnetic field are related to the functional state of the cardiovascular system and the condition of the kidneys. 2. It can be assumed that the effect of the Earth’s electromagnetic field on the pathogenetic mechanisms of kidney disease is in the opposite direction of that on the cardiovascular one. 3. Reliable gender differences in correlations between the influence of changes in the local Schumann resonance on the functional state of the cardiovascular system and kidneys were not found. 4. The connection of the Earth’s local geomagnetic field with kidney function may be another new unexplored pathogenetic mechanism in cardiorenal syndrome and noncommunicable chronic diseases. [ABSTRACT FROM AUTHOR]

The study of trimethylamine oxide (TMAO), a metabolite of gut microbiota, and heart failure and chronic kidney disease has made preliminary achievements and been summarized by many researchers, but its research in the field of cardiorenal syndrome is just beginning. TMAO is derived from the trimethylamine (TMA) that is produced by the gut microbiota after consumption of carnitine and choline and is then transformed by flavin-containing monooxygenase (FMO) in the liver. Numerous research results have shown that TMAO not only participates in the pathophysiological progression of heart and renal diseases but also significantly affects outcomes in chronic heart failure (CHF) and chronic kidney disease (CKD), besides influencing the general health of populations. Elevated circulating TMAO levels are associated with adverse cardiovascular events such as HF, myocardial infarction, and stroke, patients with CKD have a poor prognosis as well. However, no study has confirmed an association between TMAO and cardiorenal syndrome (CRS). As a syndrome in which heart and kidney diseases intersect, CRS is often overlooked by clinicians. Here, we summarize the research on TMAO in HF and kidney disease and review the existing biomarkers of CRS. At the same time, we introduced the relationship between exercise and gut microbiota, and appropriately explored the possible mechanisms by which exercise affects gut microbiota. Finally, we discuss whether TMAO can serve as a biomarker of CRS, with the aim of providing new strategies for the detection, prognostic, and treatment evaluation of CRS. [ABSTRACT FROM AUTHOR]

Left ventricular assist device (LVAD) has been highlighted as a new treatment option in the end-stage heart failure (HF). Kidney outcome after LVAD in severe cardiorenal syndrome (CRS) patients requiring kidney replacement therapy (KRT) is unclear. We investigated the impact of preoperative KRT on kidney function and survival in LVAD patients with severe CRS. A total of 50 patients followed up for at least 1 year after LVAD implantation was analyzed. The primary outcomes were estimated glomerular filtration rate and survival rate. Patients were divided into two groups depending on in-hospital KRT before LVAD implantation: the control group (n = 33) and the KRT group (n = 17). Postoperative KRT was performed for 76.5% of patients in the KRT group, and all of them discontinued KRT before discharge. There were no statistically significant differences in the degree of eGFR decline in survivors according to preoperative KRT. Although there were no statistically significant differences in the degree of eGFR decline in survivors regardless of preoperative KRT, old age (β −0.94, p < 0.01), preexisting chronic kidney disease (β −21.89, p < 0.01), and high serum creatinine (β −13.95, p < 0.01) were identified as independent predictors of post-LVAD eGFR decline. Mortality rate was higher, and more patients progressed to end-stage kidney disease in KRT group than control group. However, LVAD still can be considered as the treatment option in end-stage HF patients with severe CRS requiring KRT, especially in those with young age and previous normal kidney function. [ABSTRACT FROM AUTHOR]

Background: Individuals suffering from heart failure (HF) and cardiorenal syndrome (CRS) represent a special group of patients considering their age, multiple health issues, and treatment challenges. These factors make them more susceptible to frequent hospital stays and a higher mortality rate. UMIPIC is a multidisciplinary care model program for patients with heart failure follow up provided by internists and nurses who are experts in this entity. Our study delved into the effectiveness of this specialized care program (UMIPIC) in mitigating these risks for HF and CRS patients. Methods: We analyzed the medical records of 3255 patients diagnosed with HF and CRS types 2 and 4, sourced from the RICA registry. These patients were divided into two distinct groups: those enrolled in the UMIPIC program (1205 patients) and those under standard care (2050 patients). Using propensity score matching, we ensured that both groups were comparable. The study focused on tracking hospital admissions and mortality rates for one year after an HF-related hospital stay. Results: Patients in the UMIPIC group experienced fewer hospital readmissions due to HF compared to their counterparts (20% vs. 32%; Hazard Ratio [HR] = 0.48; 95% Confidence Interval [95% CI]: 0.40–0.57; p < 0.001). They also showed a lower mortality rate (24% vs. 36%; HR = 0.64; 95% CI: 0.54–0.75; p < 0.001). Furthermore, the UMIPIC group had fewer total hospital admissions (36% vs. 47%; HR = 0.58; 95% CI: 0.51–0.66; p < 0.001). Conclusions: The UMIPIC program, centered on holistic and ongoing care, effectively reduces both hospital admissions and mortality rates for HF and CRS patients after a one-year follow-up period. [ABSTRACT FROM AUTHOR]

Background: Heart failure (HF), chronic kidney disease (CKD), and type 2 diabetes mellitus (T2DM) are common and interrelated conditions, each with a significant burden of disease. HF and kidney disease progress through pathophysiologic pathways that culminate in end-stage disease, for which T2DM is a major risk factor. Intervention within these pathways can disrupt disease processes and improve patient outcomes. Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have been investigated in patient populations with combinations of T2DM, CKD, and/or HF. However, until recently, the effect of these agents in patients with HF with preserved ejection fraction (HFpEF) was not well studied. Main body: The aim of this review is to summarize key information regarding the interaction between HFpEF, CKD, and T2DM and discuss the role of SGLT2 inhibition in the management of patients with comorbid HFpEF and CKD, with or without T2DM. Literature was retrieved using Boolean searches for English-language articles in PubMed and Google Scholar and included terms related to SGLT2is, HFpEF, T2DM, and CKD. The reference lists from retrieved articles were also considered. Conclusion: SGLT2is are efficacious and safe in treating HFpEF in patients with comorbid CKD with and without T2DM. The totality of evidence from clinical trials data suggests there are benefits in using SGLT2is across the spectrum of left ventricular ejection fractions, but there may be a potential for different renal effects in the different ejection fraction groups. Further analysis of these clinical trials has highlighted the need to obtain more accurate phenotypes for patients with HF and CKD to better determine which patients might respond to guideline-directed medical therapies, including SGLT2is. CI confidence interval, EF ejection fraction, eGFR estimated glomerular filtration rate, HF heart failure, HHF hospitalization for HF, HR hazard ratio, LVEF left ventricular ejection fraction, SGLT2i sodium-glucose cotransporter-2 inhibitor, UACR urine albumin-creatinine ratio. a Mean value, unless otherwise stated, b SGLT2i vs. placebo, c Data reanalyzed using more conventional endpoints (≥ 50% sustained decrease in eGFR, and including renal death) (UACR at baseline not stated in trial reports) [ABSTRACT FROM AUTHOR]