Nightingale Health’s Post

Most exposed: the endothelium in chronic kidney disease Marc Vila Cuenca 1, Peter L Hordijk 2, Marc G Vervloet 1 Affiliations expand PMID: 31071222 PMCID: PMC7473805 DOI: 10.1093/ndt/gfz055 Abstract Accumulating evidence indicates that the pathological changes of the endothelium may contribute to the development of cardiovascular complications in chronic kidney disease (CKD). Non-traditional risk factors related to CKD are associated with the incidence of cardiovascular disease, but their role in uraemic endothelial dysfunction has often been disregarded. In this context, soluble α-Klotho and vitamin D are of importance to maintain endothelial integrity, but their concentrations decline in CKD, thereby contributing to the dysfunction of the endothelial lining. These hormonal disturbances are accompanied by an increment of circulating fibroblast growth factor-23 and phosphate, both exacerbating endothelial toxicities. Furthermore, impaired renal function leads to an increment of inflammatory mediators, reactive oxygen species and uraemic toxins that further aggravate the endothelial abnormalities and in turn also inhibit the regeneration of disrupted endothelial lining. Here, we highlight the distinct endothelial alterations mediated by the abovementioned non-traditional risk factors as demonstrated in experimental studies and connect these to pathological changes in CKD patients, which are driven by endothelial disturbances, other than atherosclerosis. In addition, we describe therapeutic strategies that may promote restoration of endothelial abnormalities by modulating imbalanced mineral homoeostasis and attenuate the impact of uraemic retention molecules, inflammatory mediators and reactive oxygen species. .. A clinical perspective on endothelial dysfunction in CKD may translate into reduced structural and functional abnormalities of the vessel wall in CKD, and ultimately improved cardiovascular disease.

"While modern lifestyles are a major driver, as much as 30% of mortality associated with cardiovascular disease occurs in individuals without modifiable risk factors,” said Matt Sause, CEO of Roche Diagnostics. Globally, about 1 in 5 people have elevated Lp(a), which is largely unaffected by lifestyle changes like diet and exercise. While non-genetic factors such as menopause, kidney and liver diseases, and hyperthyroidism can influence Lp(a) levels, they are mostly (>90%) determined by genetic variations in the LPA gene. Elevated Lp(a) is especially common among women and people of African descent. High Lp(a) levels contribute to lipid buildup in artery walls, increasing the risk of cardiovascular events. Therefore, Lp(a) testing is becoming an important tool for assessing cardiovascular risk and is expected to be part of routine diagnostics in the future. Read more here: https://lnkd.in/gYi9MFsy

Metabolic dysfunction–associated steatohepatitis (MASH), formerly called nonalcoholic steatohepatitis (NASH), is a severe liver disease. MASH involves fat buildup, liver inflammation, and cell injury, often leading to fibrosis. With rising obesity and type 2 diabetes, MASH cases are growing globally. It was the second leading reason for liver transplants in 2019. Today, the FDA has approved only one medication for NASH treatment: Rezdiffra (resmetirom), along with diet and exercise. Testing Tirzepatide: Researchers conducted a phase 2 clinical trial to assess tirzepatide’s effectiveness. Tirzepatide is a new drug that targets two receptors, GIP and GLP-1, known to help with insulin production and reducing appetite. The trial included 190 participants with confirmed MASH and moderate to severe fibrosis. They were randomly assigned to receive either tirzepatide (at 5 mg, 10 mg, or 15 mg) or a placebo once a week for 52 weeks. The main goal was to see if tirzepatide could resolve MASH without worsening fibrosis. ..... ..... #Mounjaro #Zepbound #Obesity #Diabetes #NASH #Liver

Today on International #GlobalFattyLiverDay, I would like to highlight a new #review #paper suggesting that #cardiovasculardisease is more prevalent in patients living with #MASH than in patients with other liver diseases. The authors, including three from @NovoNordisk, performed a literature review evaluating #CVD outcome studies in adults with histologically confirmed MASH. 🩺 MASH is a severe liver disease characterized by the accumulation of fat in the liver (hepatic steatosis) along with inflammation and liver cell damage. Worldwide, fatty liver diseases (MASH and the less severe form MASLD) affect more than 115 million people and the number is increasing.   Why is the link between MASH and CVD interesting? It has long been known that liver diseases lead to elevated risk of developing cardiovascular disease. But in this study, it becomes evident that the risk of experiencing major cardiovascular events such as #stroke or #heartfailure is suggestively higher – maybe even 3 to 4 times higher - for people living with MASH than for other liver patient subgroups. This study also concludes that cardiovascular health should be carefully and proactively managed in patients with MASH.🩺   MASH is closely linked to metabolic syndrome, a cluster of conditions that includes obesity, high blood pressure, high blood sugar, and abnormal cholesterol or triglyceride levels and often insulin resistance. Many of these diseases and biomarkers of disease interlink, and that is why we must treat the drivers of metabolic syndrome to treat all at once.   Today, I hope that you will join me in creating awareness to the unmet need of millions of patients living with MASH, which is often accompanied by other diseases and comorbidities such as type 2 diabetes, kidney disease, #obesity, and liver diseases. 📢 Let’s speak up and talk about these diseases that people rarely know much about but that affect so many. That is why we at @NovoNordisk work hard to innovate every day to meet the unmet needs of these patients. 🤍 #innovation #pharma #science #metabolicsyndrome https://lnkd.in/ddsUcRxw

Sains Malaysiana 53(8)(2024): 1843-1858 https://lnkd.in/g_Twz8hK Establishing the Association between Ankylosing Spondylitis and Its Comorbidities Based on Their Shared Pathways (Penentuan Asosiasi antara Ankylosing Spondylitis dan Komorbiditinya Berdasarkan Tapak Jalan Sepunya) ABSTRACT Ankylosing spondylitis (AS) is an autoimmune and inflammatory arthritis associated with various comorbidities, such as axial spondyloarthritis (axSpA), cardiovascular disease (CD), Guillain-Barre syndrome (GBS), rheumatic fever (RF), and vasculitis (Vs). The co-occurrence of these comorbidities underlies the molecular mechanisms of complex biological interactions shared by dysfunctional pathways. We used network biology and computational methods to establish association between biological processes and molecular mechanisms in AS and its comorbidities. The findings showed significant association between twelve shared pathways in AS and its comorbidities. These shared pathways are associated with pathobiological processes, such as immune responses, inflammatory responses and cellular signaling responses, in AS and its comorbidities. Nine of these pathways are involved in signaling, two are involved in the metabolic processes, and one is involved in the regulatory processes in AS and its comorbidities. In conclusion, this work highlights specific and common shared pathways in AS and its comorbidities. These findings provide information on key shared pathways that can be used to explain the pathobiological processes of AS and its comorbidities and can help in therapeutic discovery towards accurate diagnosis and effective treatment.

Are 5 stages of kidney disease classification really needed? Kidney Disease Quality Outcome Initiative (K/DOQI) has defined and classified the stages of kidney diseases (chronic kidney diseases). Since the inception of CKD stages as first published by KDIGO in 2002, concerns have been expressed about the definition and classification of CKD. The position paper published in Kidney International June 2005 issue in response to a survey by nephrologists worldwide, quotes “about one third find it ether not useful or would prefer modifications.” So why are we revisiting the question? Going back to the original intentions of the consensus writers (KDIGO 2005), the attempt to define and classify kidney diseases was to 1) “provide a CLEAR understanding to both nephrology and NONNEPHROLOGY communities” and 2) “develop global consensus for the adoption of a SIMPLE definition and classification system” Does the definition and especially the classification of CKD as defined by K/DOQI succeed in providing a clear (unambiguous) understanding to the general community? The answer is an emphatic NO. The idea behind defining things is to make it easy enough for most people to grasp a basic understanding. If the essential definition itself sows confusion, I think it is recommended we revisit the definition. So as per current definition including classification of CKD- Defined by a glomerular filtration rate (GFR) of less than 60 mL/min/1.73 m2, albuminuria of at least 30 mg per 24 hours, or markers of kidney damage (eg, hematuria or structural abnormalities such as polycystic or dysplastic kidneys) persisting for more than 3 months. Though the definition hits all the necessary points needed- it does not tell us that one can still have CKD- stages I and II in otherwise healthy people who have no proteinuria or blood in urine or morphological aberration of kidneys. Even when their GFR is above 60 ml/min For comparison, our neighbors across the Atlantic (UK Kidney Association) make it explicitly clear that patients with eGFR >60 should NOT be classified as having CKD unless they have other markers of kidney disease. So do we still need to classify people who have no evidence of kidney dysfunction (urine/ultrasound) as having CKD if their GFR (derived from serum creatinine value) happens to be 89 ml/min. The answer is clearly no but the current classification will stage them as Stage II CKD which appears preposterous to me. It is one thing to have classification based from epidemiologic/public health perspective but it is clearly not helpful when we are frivolously diagnosing people as having CKD when in fact they do not have any evidence of kidney problem whatsoever. The responsibility falls on the shoulders of interested stakeholders (Kidney Health Inititiative/National Kidney Foundation) and also kidney disease leaders to call for action for redefining stages of CKD. References: https://lnkd.in/gThYZMej

🩺 C-Peptide: A Powerful Predictor of Cardiovascular and Overall Mortality? 🔍 This study highlighted the role of C-peptide levels in predicting cardiovascular and all-cause mortality, OUTPERFORMING traditional insulin resistance markers such as HOMA-IR and QUICKI. 😵 📖 Key Findings: 🔬 Fasting C-peptide levels predicted cardiovascular and overall mortality better than other studied measures: AUC = 0.62 and 0.60, respectively, compared to ≤0.58 and ≤0.57 for other markers (P < 0.001). 📊 C-Peptide and Mortality Risk: 🔗 After adjusting for confounders, individuals in the highest C-peptide quartile had significantly higher risks of: ☝ Cardiovascular death: HR = 1.60 (95% CI: 1.07–2.39). ✌ Overall mortality: HR = 1.72 (95% CI: 1.34–2.21) ⚠️ "The increased hazards associated with the highest vs the lowest C-peptide quartile were comparable to that of being male, a current smoker, or having elevated C-reactive protein levels." 🩺 The attributable risk of cardiovascular death associated with C-peptide levels in the upper quartile was ~52%. 🤗 Why Is Insulin Resistance Important? Understanding IR and related biomarkers like C-peptide helps identify at-risk individuals earlier, allowing for tailored interventions to mitigate the genesis or progression of chronic disease. 💡 Conclusion: C-peptide levels provide a robust, independent marker for assessing cardiovascular and all-cause mortality, even when controlling for an array of confounders. This underscores its potential as a key biomarker for improving risk prediction in clinical practice. 🤓 For the full study, read here: https://lnkd.in/gwFiUKbk Do you run C-peptide for your patients as a risk stratification metric? Drop a comment below! 🤔📉❤️

🌟 Unlocking the Power of Statins Beyond Cholesterol! 🌟 Recent studies reveal that statins, traditionally known for lowering cholesterol, are making waves in the realm of inflammation management. These medications are now recognized for their ability to modulate immune responses and target critical pathways in various diseases. 🔍 Key Insights: - Statins inhibit the CD40:CD40L signaling pathway, crucial in autoimmune and inflammatory conditions. - They showcase anti-inflammatory effects by reducing immune activity. - Potential applications span chronic diseases like asthma and multiple sclerosis, as well as cardiovascular issues. With tailored therapeutic approaches, statins could revolutionize treatment strategies by addressing both lipid levels and inflammation. 💡 This research opens doors for clinicians to explore specific statin roles in inflammatory pathways—paving the way for enhanced patient outcomes! 👉 Dive deeper into this groundbreaking study by clicking on the link! #AutoimmuneDiseases #CardiovascularHealth #HealthcareInnovation #Inflammation #MedicalResearch #Pharma #PharmaceuticalCompanies #Publications #Statins #MarketAccess #MarketAccessToday

📢 Exploring the Protective Role of Lactoferrin in Atherosclerosis Cardiovascular diseases, including stroke, hypertension and heart failure, have a significant impact on global health and are often due to atherosclerosis. This disease, characterized by endothelial cell dysfunction, smooth muscle proliferation, cholesterol accumulation and chronic inflammation, leads to serious complications such as heart attacks. At Mercurius Production, we are committed to advancing the understanding and benefits of lactoferrin (Lf) in combating atherosclerosis and promoting cardiovascular health. 🔍 Key Points on Lactoferrin's Potential Role: 1.⁠ ⁠Correlation with Atherosclerosis Risk: o Endogenous Lf levels correlate with the severity of coronary stenosis and cardiovascular events. o Higher Lf levels are observed in patients with significant coronary stenosis and ischemic heart disease. 2.⁠ ⁠Improving Cholesterol Metabolism: o Bovine Lf (bLf) can increase HDL levels while reducing "bad cholesterol" (triacylglycerides, non-esterified fatty acids). o bLf promotes bile acid excretion, lowering liver cholesterol and alleviating atherosclerosis symptoms. 3.⁠ ⁠Inhibiting Foam Cell Formation: o bLf may neutralize modified LDL's negative charge, inhibiting macrophage binding and reducing foam cell formation. 4.⁠ ⁠Binding to Advanced Glycation End Products (AGEs): o Lf can bind to AGEs, potentially impacting oxidative stress and atherosclerotic disease pathogenesis. 5.⁠ ⁠Reducing Homocysteine and Leptin Levels: o bLf intake significantly lowers these markers, crucial in preventing cardiovascular disease. 6.⁠ ⁠Anti-inflammatory and Antioxidant Properties: o Lf inhibits excessive inflammatory responses and oxidative stress, critical factors in atherosclerosis development. These promising findings underscore Lactoferrin's potential as a preventive and therapeutic agent in atherosclerosis management. We look forward to continuing our research and contributing to innovative healthcare solutions. 🌐 Learn more on our website: https://lnkd.in/ejqMUkwg #lactoferrin #health #protein #atherosclerosis #germany #europe

If you don't take steps to reverse fatty liver disease, it can progress and lead to serious health consequences: Inflammation: Fatty liver can worsen, causing ongoing liver inflammation. Scarring: This inflammation can lead to the development of scar tissue (fibrosis) in the liver. Cirrhosis: As fibrosis advances, it can result in cirrhosis, which severely impairs liver function. Liver Failure: Cirrhosis can eventually lead to liver failure, a life-threatening condition. Increased Cancer Risk: Fatty liver disease raises the risk of liver cancer. Cardiovascular Issues: It's often associated with conditions like obesity and diabetes, increasing the risk of heart disease. Metabolic Problems: Fatty liver is linked to insulin resistance and metabolic syndrome, increasing the risk of diabetes. Digestive Problems: Liver dysfunction can affect digestion and nutrient absorption. Complications Beyond Liver: Fatty liver can contribute to systemic inflammation and impact other organs.