Cardiorenal Metabolic Syndrome Research Articles

Abstract P3190: Renal Tubular Mitochondrial Akt1 Modulates Cardiorenal Metabolic Syndrome

Metabolic syndrome-induced cardiomyopathy is a significant risk factor for cardiovascular diseases (CVDs). The proximal tubular cells of the kidney play a crucial role in regulating glucose and lipid metabolism. Mitochondrial dysfunction in these cells has been linked to the development of metabolic syndrome-induced cardiac dysfunction. AKT1, a serine/threonine protein kinase, regulates mitochondrial function. In this study, we investigated the effects of renal proximal tubular mitochondrial AKT1 on metabolic syndrome-induced cardiomyopathy in transgenic mice. We generated transgenic mouse lines, KMioxCAKT, with inducible overexpression of mitochondrial AKT1, specifically in renal proximal tubular cells. One line was induced with tamoxifen, while the other was with corn oil. Both lines were fed a high-fat diet (HFD) for 16 weeks to provoke metabolic syndrome. For renal function, although serum BUN ( p= 0.728 ) and creatinine ( p=0.622 ) were not changed, the proteinuria ( p=0.031 ) and the urine KIM-1 ( p=0.012 ) were decreased in tamoxifen-induced KMioxCAKT. The glomerulosclerosis index ( p =0.027), tubulointerstitial fibrosis score ( p =0.032), tubular dilatation score ( p =0.032), tubular vacuolation score ( p =0.031), and tubular casts ( p =0.018) of renal histology were amended in tamoxifen-induced KMioxCAKT. The fasting glucose level ( p =0.015); the 15 to 120 minutes glucose levels ( p =0.020); the fasting insulin level ( p=0.037 ), and insulin resistance measured by Homeostatic Model Assessment for Insulin Resistance ( p=0.005 ) were reduced in metabolic syndrome with augmentation of renal tubular mitochondrial AKT1. In addition, tamoxifen-induced KMioxCAKT mice had significantly attenuated cardiac hypertrophy in the heart compared to corn oil-induced KMioxCAKT. Our results suggest that enhancing renal proximal tubular mitochondrial AKT1 could ameliorate the cardiorenal metabolic syndrome.

Healthcare Costs Associated with the Development and Combination of Cardio-Renal-Metabolic Diseases.

Background The Cardio-Renal-Metabolic Syndrome (CRM) is a constellation of conditions that includes atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), chronic kidney disease (CKD) and type 2 diabetes (T2D). The economic consequences of developing each of these comorbidities in the context of the others has not been studied. Methods We used the electronic medical records of Kaiser Permanente Northwest (KPNW) to identify 387,985 members aged 18 or older who had a serum creatinine measured between 2005 and 2017. Patients were followed through 2019. We used a statistical approach that assesses time dependency for continuous measures; the total observation period for each patient was divided into quarters (91-day increments), and each patient contributed a record for every quarter in which they were members of the health plan. CRM status was determined for each quarter. Results The incremental annualized cost of each of these chronic diseases was similar regardless of which other conditions were present when the new condition developed. Overall costs increased by $10,316 (130%) when CKD developed, $6,789 (84%) for T2D, $21,573 (304%) for ASCVD, and $36,522 (475%) for HF. However, as a result of pre-diagnosis costs being higher as more conditions were present, the percentage increases in costs associated with incidence were lower when more prevalent conditions existed. Conclusions Onset of any new CRM condition drove substantial increase in health care costs. Our findings indicate a clear interplay of CRM conditions and emphasize the need for better simultaneous prevention and management of these disease states to reduce the economic burden on healthcare systems.

Type 2 diabetes: treatment recommendations for reducing the risk of complications.

Nurses should recognise type 2 diabetes as a cardiorenal metabolic syndrome that requires the holistic management of blood glucose, blood pressure, lipid levels and lifestyle factors. It is also important that nurses can identify, prevent and manage complications associated with type 2 diabetes, such as cardiovascular disease, retinopathy, nephropathy, foot health issues and psychological effects. This article explains the latest national guidelines on managing type 2 diabetes in adults, including the recommendations for pharmacological treatment, thereby supporting nurses to provide effective care for people with this condition.

The Conicity Index in Identification of Cardiorenal Metabolic Syndrome Patients at Increased Risk for Complications

The Conicity Index in Identification of Cardiorenal Metabolic Syndrome Patients at Increased Risk for Complications

Exploring the Complex Relationship between Diabetes and Cardiovascular Complications: Understanding Diabetic Cardiomyopathy and Promising Therapies

Diabetes mellitus (DM) and cardiovascular complications are two unmet medical emergencies that can occur together. The rising incidence of heart failure in diabetic populations, in addition to apparent coronary heart disease, ischemia, and hypertension-related complications, has created a more challenging situation. Diabetes, as a predominant cardio-renal metabolic syndrome, is related to severe vascular risk factors, and it underlies various complex pathophysiological pathways at the metabolic and molecular level that progress and converge toward the development of diabetic cardiomyopathy (DCM). DCM involves several downstream cascades that cause structural and functional alterations of the diabetic heart, such as diastolic dysfunction progressing into systolic dysfunction, cardiomyocyte hypertrophy, myocardial fibrosis, and subsequent heart failure over time. The effects of glucagon-like peptide-1 (GLP-1) analogues and sodium-glucose cotransporter-2 (SGLT-2) inhibitors on cardiovascular (CV) outcomes in diabetes have shown promising results, including improved contractile bioenergetics and significant cardiovascular benefits. The purpose of this article is to highlight the various pathophysiological, metabolic, and molecular pathways that contribute to the development of DCM and its significant effects on cardiac morphology and functioning. Additionally, this article will discuss the potential therapies that may be available in the future.

Kidney Biopsy in a Patient with Cardiorenal Metabolic Syndrome—How to Interpret Histopathology

The components of Cardiorenal Metabolic Syndrome (CRMS) include central obesity, insulin resistance, hypertension, metabolic dyslipidemia, proteinuria, and/or reduced glomerular filtration rate. Kidney biopsy is rarely performed in patients with CRMS; histopathology findings include glomerulopathy, podocytopathy, mesangial expansion and proliferation, glomerular basement thickening, global and segmental sclerosis, interstitial fibrosis and tubular atrophy, and arterial sclerosis and hyalinosis. We report a case of CRMS with slow progression during 10 years of follow-up on chronic kidney disease (CKD). The middle-aged patient had central obesity, hypertension, dyslipidemia, cardiovascular disease, type 2 diabetes mellitus, proteinuria, and CKD stage G3b-G4. Kidney biopsy, performed 3 years after the first presentation, led to the diagnosis of chronic thrombotic microangiopathy (TMA) and complement-associated glomerulopathy. This was not compatible with the medical history and the course of the disease, and previous kidney biopsy review showed metabolic nephropathy with glomerulomegaly, global and segmental glomerulosclerosis, tubular atrophy and interstitial fibrosis, arteriosclerosis, and lipid embolus in the lumen of one artery, and found neither TMA features nor C3 deposition. The reported case demonstrates the importance of an accurate and thoughtful reading and interpretation of kidney biopsy, and stresses that disregarding medical history may potentially mislead and alter the understanding of the true cause of CKD.

Kidney Dysfunction in Central Obesity Associated Metabolic Disorders

Epidemiological data confirm the association of the metabolic syndrome (MS) with CKD, causality, however, is still debated. The complex multimorbid pathology known as cardiorenal MS is characterized by interrelated and intertwined, mutually aggravating conditions, caused by shared factors with synergistic, additive, multiplicative effects. Early identification of patients at increased CVD and mortality risk, associated even with mild kidney dysfunction, by simple predictive biomarkers applicable from the primary care setting, may optimize management and lessen the public health burden. In a central Romanian population, 201 middle-aged control subjects and MS patients were investigated, diagnosed by the IDF-criteria, with mandatory central obesity but no microalbuminuria or hyperuricemia included in the diagnostic system. Renal dysfunction was assessed by eGFR (estimated glomerular filtration rate), regarded useful in early CKD detection, calculated by the novel CKD-EPI creatinine formula. eGFR was significantly reduced in cases in comparison with controls, and an increased risk for kidney dysfunction associated with the MS, as well as with dysglycemia+hypertension+low HDL-C - considered critical components compared to other combinations within the patient group (OR: 2.05 and 1.46; p<0.05). In case of the MS, eGFR correlated with both disease components and etiological factors, such as weight-adjusted-waist index, blood pressure and uric acid, HOMA-assessed beta-cell function and age, or dysglycemia, hypertension, dyslipidemia, hyperuricemia and cardiovascular disease onset (r: 0.37,-0.24,-0.36,-0.31,-0.49,-0.28,-0.27,-0.53,-0.49,-0.28; p<0.05). In conclusion, reduced eGFR appears related to disease development and progression in central obesity-associated MS. Timely detection may improve risk assessment and intervention by targeted preventive measures and novel therapeutics with multisystem impact.

Clinical complexity and diabetes: a multidimensional approach for the management of cardiorenal metabolic syndrome

Diabetes mellitus (DM) is one of the fastest-growing health emergencies of the 21st century, and one of the chronic diseases with the highest socio-economic impact on health care systems. DM is the main cause of chronic kidney disease, and is associated with a significant increase in cardiovascular risk and clinical and care complexity. The presence of a constellation of cardiac, metabolic, and renal diseases, in a complex patient with DM, constitutes the CardioRenal Metabolic Syndrome (CRMS). The management of these patients should include a paradigm shift from a reactive strategy to a proactive approach, and the integration of territorial, hospital and social assistance services according to the Chronic Care Model (CCM). Complexity science suggests an alternative model in which disease and health arise from complex, dynamic, and unique interactions among the different components of the overall system. The hospital should be viewed as a highly specialized hub of the chronic care system, which interacts with the outpatient specialist and primary care. In order to create effective communication among territorial care units and highly specialized hospitals, levels of clinical complexity are here proposed and included in a multidimensional management model for the complex patient with diabetes and cardiorenal comorbidity.

Diagnosing Arterial Stiffness in Pregnancy and Its Implications in the Cardio-Renal-Metabolic Chain.

Cardio-renal and metabolic modifications during gestation are crucial determinants of foetal and maternal health in the short and long term. The cardio-renal metabolic syndrome is a vicious circle that starts in the presence of risk factors such as obesity, hypertension, diabetes, kidney disease and ageing, all predisposing to a status dominated by increased arterial stiffness and alteration of the vascular wall, which eventually damages the target organs, such as the heart and kidneys. The literature is scarce regarding cardio-renal metabolic syndrome in pregnancy cohorts. The present paper exposes the current state of the art and emphasises the most important findings of this entity, particularly in pregnant women. The early assessment of arterial function can lead to proper and individualised measures for women predisposed to hypertension, pre-eclampsia, eclampsia, and diabetes mellitus. This review focuses on available information regarding the assessment of arterial function during gestation, possible cut-off values, the possible predictive role for future events and modalities to reverse or control its dysfunction, a fact of crucial importance with excellent outcomes at meagre costs.

Bergamot leaf extract treats cardiorenal metabolic syndrome and associated pathophysiological factors in rats fed with a high sugar fat diet

Bergamot citrus (Citrus bergamia Risso et Poiteau), have been used as a strategy to prevent or treat comorbidities associated with metabolic syndrome parameters, such as cardiorenal metabolic syndrome (CRMS). The aim was to test the effect of bergamot leaf extract on CRMS and associated pathophysiological factors in rats fed with a high sugar-fat diet. Animals were divided into two experimental groups with control diet (Control, n = 30) and high sugar-fat diet (HSF, n = 30) for 20 weeks. Once CRMS was detected, animals were redivided to begin the treatment with Bergamot Leaf Extract (BLE) by gavage (50 mg/kg) for 10 weeks: control diet + placebo (Control, n = 09), control diet + BLE (Control + BLE, n = 09), HSF diet + placebo (HSF, n = 09), HSF + BLE (n = 09). Evaluation included nutritional, metabolic and hormonal analysis; and renal and cardiac parameters. HSF groups presented obesity, dyslipidemia, hypertension, hyperglycemia, hyperinsulinemia, insulin resistance. BLE showed protection against effects on hypertriglyceridemia, insulin resistance, renal damage, and structural and functional alterations of the heart. Conclusion: Bergamot leaf extract shows potential as a therapeutic to treat CRMS in animals fed with a high sugar-fat diet.

Cardiorenal metabolic syndrome: reaching a consensus in shared care

Cardiorenal metabolic syndrome is a group of interactive conditions affecting cardiovascular, renal and metabolic systems. Treatment for this multidimensional syndrome is complex, partly as a result of the current lack of definition and inclusion and exclusion criteria. Symptoms can fluctuate and follow a nonconforming pattern, and treatment is dependent on the severity of the underlying conditions involved. A multidisciplinary service model can integrate care for patients with cardiorenal metabolic syndrome and promote shared decision making. Research indicates that the use of an integrated care model also has the potential to improve clinical outcomes, while strategies such as interdisciplinary education and the promotion of self-management opportunities for individuals can improve quality of life.

Development and Current Role of Sodium Glucose Cotransporter Inhibition in Cardiorenal Metabolic Syndrome.

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.

The relationship of asymptomatic hyperuricemia and metabolic syndrome in cardio renal patients

Background and Aims: The association between hyperuricemia and Mets has been reveled for a long time. Both serum uric acid (SUA) levels and metabolic syndrome are associated with progression of kidney and cardiovascular diseases and cardiorenal metabolic syndrome. Aim: The purpose of the study was to evaluate the relationship of hyperuricemia and metabolic syndrome (MetS) in cardiorenal patients

The role of sodium-glucose cotransporter 2 inhibitors in the treatment of type 2 diabetes: from clinical research to real practice

In type 2 diabetes mellitus (T2DM), the development and progression of cardiovascular diseases occurs, which allows it to be considered as a cardiorenal metabolic syndrome. This should be taken into account when choosing hypoglycemic drugs. Patients with T2DM receiving insulin therapy often have a long history of diabetes, cardiovascular disease, chronic kidney disease, obesity, and need to be prescribed high doses of insulin and/or complex insulin therapy regimens to maintain glycemic control, which does not always lead to the achievement of target levels of glycemia and glycated hemoglobin (HbA1c). Adding to any insulin therapy regimen drugs from the class of sodium-glucose cotransporter type 2 inhibitors (SGLT-2), which have proven their cardio- and renoprotective properties, seems to be a rational combination in patients with T2DM and may have a number of advantages. The article presents 4 clinical examples of dapagliflozin administration, a drug from the SGLT2 class, to patients who are on insulin therapy, having T2DM with a long history (10–26 years), as well as cardiovascular diseases, chronic kidney disease, and obesity. Dapagliflozin administration allowed to improve glycemic control, to stabilize the insulin dose, as well as reduce body weight without increasing the frequency of serious episodes of hypoglycemia in patients who initially received large doses of insulin. In the long term, we can expect reduction of the progression of cardiovascular risks and the risks of hospitalization due to existing complications of the disease.

The complex pa¬tient with diabetes and cardio-renal comorbidities: a mana¬gement model proposal

Type 2 diabetes mellitus (DM) is a metabolic disorder and its prevalence has been increasing in the world population and represents one of the chronic diseases with the highest socioeconomic impact on the health systems. It is expected that in the next decade life expectancy and population aging will increase with the consequences of the increasing incidence of diabetes and its associated comorbidities. (DM) is the main cause of chronic kidney disease and it is associated with a significant increasing in cardiovascular risk. The coexistence of cardiac and kidney diseases on a metabolic basis, named “cardiorenal metabolic syndrome”, in elderly patients affected by multimorbidity increase their clinical and care complexity. In order to assess clinical complexity it is necessary to change paradigm from a reactive approach to a proactive one and the integration of territorial, hospital and social services according to the Chronic Care Model (CCM) is important. The proactive management of the complex patient suffering from chronic diseases and multimorbidity has been implemented at the National ARNAS Civico Hospital in Palermo with the MUSE (Multidimensional aSsessment of Elderly) project. The interaction between hospital and territorial services to respond to patients’ needs should be a priority. The hospital must therefore be conceived as a highly specialized center for chronic disease management that works with primary care according to a multidimensional and multidisciplinar model of care reducing rehospitalization and negative outcomes in patients affected by chronic diseases. KEY WORDS diabetes mellitus type2; comorbidity; management model; complexity; cardiorenal syndrome.

Range of adiposity and cardiorenal syndrome.

Obesity and obesity-related co-morbidities, diabetes mellitus, and hypertension are among the fastest-growing risk factors of heart failure and kidney disease worldwide. Obesity, which is not a unitary concept, or a static process, ranges from alterations in distribution to the amount of adiposity. Visceral adiposity, which includes intraabdominal visceral fat mass and ectopic fat deposition such as hepatic, cardiac, or renal, was robustly associated with a greater risk for cardiorenal morbidity than subcutaneous adiposity. In addition, morbid obesity has also demonstrated a negative effect on cardiac and renal functioning. The mechanisms by which adipose tissue is linked with the cardiorenal syndrome (CRS) are hemodynamic and mechanical changes, as well neurohumoral pathways such as insulin resistance, endothelial dysfunction, nitric oxide bioavailability, renin-angiotensin-aldosterone, oxidative stress, sympathetic nervous systems, natriuretic peptides, adipokines and inflammation. Adiposity and other associated co-morbidities induce adverse cardiac remodeling and interstitial fibrosis. Heart failure with preserved ejection fraction has been associated with obesity-related functional and structural abnormalities. Obesity might also impair kidney function through hyperfiltration, increased glomerular capillary wall tension, and podocyte dysfunction, which leads to tubulointerstitial fibrosis and loss of nephrons and, finally, chronic kidney disease. The development of new treatments with renal and cardiac effects in the context of type 2 diabetes, which improves mortality outcome, has highlighted the importance of CRS and its prevalence. Increased body fat triggers cellular, neuro-humoral and metabolic pathways, which create a phenotype of the CRS with specific cellular and biochemical biomarkers. Obesity has become a single cardiorenal umbrella or type of cardiorenal metabolic syndrome. This review article provides a clinical overview of the available data on the relationship between a range of adiposity and CRS, the support for obesity as a single cardiorenal umbrella, and the most relevant studies on the recent therapeutic approaches.

CARDIO-RENAL METABOLIC SYNDROME AND PRO-INFLAMMATORY FACTORS: THE DIFFERENTIAL EFFECTS OF DIETARY CARBOHYDRATE AND FAT.

We aimed to evaluate whether a high carbohydrate or a high fat diet differs in alteration of the inflammatory and metabolic risk factors in cardio-renal metabolic syndrome in rats. Twelve male Wister rats were randomly divided into two groups: one received diet 1 standard pellet rat diet (D1) containing 10% fat, 50% carbohydrate, 25% protein and another group received diet 2 (D2) containing 59% fat, 30% carbohydrate and 11% protein for 16 weeks. Weight was recorded weekly. FSG and insulin levels were measured using an enzymatic spectrophotometric and a standard ELISA kit respectively. Inflammatory parameters including TGF-β, MCP-1, TNF-α, IL-1β, IL-6 in the renal and cardiac tissues of rats were evaluated by ELISA technique. Food intake in D1 and D2 groups increased in the study period, however food intake in D2 group was significantly higher compared with D1 group. FSG, HOMA and TG concentrations in D2 group were significantly higher compared to D1 group. Moreover, TGF-β and MCP-1 concentrations in the renal tissues of D2 group and TNF-α in the cardiac tissues of D1 group were significantly higher compared with D1 group (P<0.05). Positive associations between IL-1β and TG and between HOMA, FSG with TGF-β and MCP-1 in the renal tissue of animals were also identified.

Effect of Gamma-Oryzanol as Therapeutic Agent to Prevent Cardiorenal Metabolic Syndrome in Animals Submitted to High Sugar-Fat Diet.

Background: The high consumption of fat and sugar contributes to the development of obesity and co-morbidities, such as diabetes, and cardiovascular and kidney diseases. Different strategies have been used to prevent these diseases associated with obesity, such as changes in eating habits and/or the addition of dietary components with anti-inflammatory and anti-oxidant properties, such as gamma-oryzanol (γOz) present mainly in bran layers and rice germ. Methods: Animals were randomly divided into four experimental groups and fed ad libitum for 20 weeks with control diet (C, n = 8), control diet + γOz (C + γOz, n = 8), high-sugar and high-fat diet (HSF, n = 8), and high-sugar and high-fat diet + γOz (HSF + γOz, n = 8). HSF groups also received water + sucrose (25%). The dose of γOz was added to diets to reach 0.5% of final concentration (w/w). Evaluation in animals included food and caloric intake, body weight, plasma glucose, insulin, triglycerides, uric acid, HOMA-IR, glomerular filtration rate, protein/creatinine ratio, systolic blood pressure, and Doppler echocardiographic. Results: Animals that consumed the HSF diet had weight gain compared to group C, increased insulin, HOMA, glucose and triglycerides, there were also atrial and ventricular structural alterations, deterioration of systolic and diastolic function, decreased glomerular filtration rate, and proteinuria. Gamma-oryzanol is significantly protective against effects on body weight, hypertriglyceridemia, renal damage, and against structural and functional alteration of the heart. Conclusion: Gamma-oryzanol shows potential as a therapeutic to prevent Cardiorenal Metabolic Syndrome.

Distinct Endothelial Cell Responses in the Heart and Kidney Microvasculature Characterize the Progression of Heart Failure With Preserved Ejection Fraction in the Obese ZSF1 Rat With Cardiorenal Metabolic Syndrome.

The combination of cardiac and renal disease driven by metabolic risk factors, referred to as cardiorenal metabolic syndrome (CRMS), is increasingly recognized as a critical pathological entity. The contribution of (micro)vascular injury to CRMS is considered to be substantial. However, mechanistic studies are hampered by lack of in vivo models that mimic the natural onset of the disease. Here, we evaluated the coronary and renal microvasculature during CRMS development in obese diabetic Zucker fatty/Spontaneously hypertensive heart failure F1 hybrid (ZSF1) rats. Echocardiographic, urine, and blood evaluations were conducted in 3 groups (Wistar-Kyoto, lean ZSF1, and obese ZSF1) at 20 and 25 weeks of age. Immunohistological evaluation of renal and cardiac tissues was conducted at both time points. At 20 and 25 weeks, obese ZSF1 rats showed higher body weight, significant left ventricular hypertrophy, and impaired diastolic function compared with all other groups. Indices of systolic function did not differ between groups. Obese ZSF1 rats developed hyperproliferative vascular foci in the subendocardium, which lacked microvascular organization and were predilection sites of inflammation and fibrosis. In the kidney, obese ZSF1 animals showed regression of the peritubular and glomerular microvasculature, accompanied by tubulointerstitial damage, glomerulosclerosis, and proteinuria. The obese ZSF1 rat strain is a suitable in vivo model for CRMS, sharing characteristics with the human syndrome during the earliest onset of disease. In these rats, CRMS induces microvascular fibrotic responses in heart and kidneys, associated with functional impairment of both organs.

Mitochondrial functional impairment in response to environmental toxins in the cardiorenal metabolic syndrome.

Environmental toxins can promote cardiovascular, metabolic, and renal abnormalities, which characterize the cardiorenal metabolic syndrome (CRS). Heavy metals, such as mercury and arsenic, represent two of the most toxic pollutants. Exposure to these toxins is increasing due to increased industrialization throughout much of the world. Studies conducted to understand the impact of environmental toxins have shown a major impact on mitochondrial structure and function. The maladaptive stress products caused by these toxins, including aggregated proteins, damaged organelles, and intracellular pathogens, can be removed through autophagy, which is also known as mitophagy in mitochondria. Although the underlying mechanisms involved in the regulation of mitophagy in response to pollution are not well understood, accumulating evidence supports a role for maladaptive mitochondrial responses to environmental pollution in the pathogenesis of the CRS. In this review, we discuss the ongoing research, which explores the mechanisms by which these toxins promote abnormalities in mitophagy and associated mitochondrial dysfunction and the CRS.