Advances in the Pathogenesis and Treatment of Resistant Hypertension.

Hypertension is a prevalent chronic disease associated with an increased risk of cardiovascular (CV) premature death, and its severe form manifests as resistant hypertension (RH). The accurate prevalence of resistant hypertension is difficult to determine due to the discrepancy in data from various populations, but according to recent publications, it ranges from 6% to 18% in hypertensive patients. However, a comprehensive understanding of the pathogenesis and treatment of RH is essential. This review emphasizes the importance of identifying the causes of treatment resistance in antihypertensive therapy and highlights the utilization of appropriate diagnostic methods. We discussed innovative therapies such as autonomic neuromodulation techniques like renal denervation (RDN) and carotid baroreceptor stimulation, along with invasive interventions such as arteriovenous anastomosis as potential approaches to support patients with inadequate medical treatment and enhance outcomes in RH.

Cardiovascular Diseases: Therapeutic Potential of SGLT-2 Inhibitors.

Cardiovascular diseases (CVD) are a global health concern, affecting millions of patients worldwide and being the leading cause of global morbidity and mortality, thus creating a major public health concern. Sodium/glucose cotransporter 2 (SGLT2) inhibitors have emerged as a promising class of medications for managing CVD. Initially developed as antihyperglycemic agents for treating type 2 diabetes, these drugs have demonstrated significant cardiovascular benefits beyond glycemic control. In our paper, we discuss the role of empagliflozin, dapagliflozin, canagliflozin, ertugliflozin, and the relatively recently approved bexagliflozin, the class of SGLT-2 inhibitors, as potential therapeutic targets for cardiovascular diseases. All mentioned SGLT-2 inhibitors have demonstrated significant cardiovascular benefits and renal protection in clinical trials, in patients with or without type 2 diabetes. These novel therapeutic approaches aim to develop more effective treatments that improve patient outcomes and reduce the burden of these conditions. However, the major scientific achievements of recent years and the many new discoveries and mechanisms still require careful attention and additional studies.

Chronic Kidney Disease as a Comorbidity in Heart Failure.

Heart failure (HF) is one of the greatest problems in healthcare and it often coexists with declining renal function. The pathophysiology between the heart and the kidneys is bidirectional. Common mechanisms leading to the dysfunction of these organs result in a vicious cycle of cardiorenal deterioration. It is also associated with difficulties in the treatment of aggravating HF and chronic kidney disease (CKD) and, as a consequence, recurrent hospitalizations and death. As the worsening of renal function has an undeniably negative impact on the outcomes in patients with HF, searching for new treatment strategies and identification of biomarkers is necessary. This review is focused on the pathomechanisms in chronic kidney disease in patients with HF and therapeutic strategies for co-existing CKD and HF.

Structural and Functional Changes in Aging Kidneys.

The renal condition is one of the crucial predictors of longevity; therefore, early diagnosis of any dysfunction plays an important role. Kidneys are highly susceptible to the aging process. Unfavorable conditions may lead to a significant disturbance of the body's homeostasis. Apart from physiological changes, there are some conditions such as hypertension, diabetes or obesity which contribute to the acceleration of the aging process. A determination of macroscopic and microscopic changes is essential for assessing the progression of aging. With age, we observe a decrease in the volume of renal parenchyma and an increase in adipose tissue in the renal sinuses. Senescence may also be manifested by the roughness of the kidney surface or simple renal cysts. The main microscopic changes are a thickening of the glomerular basement membrane, nephrosclerosis, an accumulation of extracellular matrix, and mesangial widening. The principal aspect of stopping unfavorable changes is to maintain health. Studies have shown many useful ways to mitigate renal aging. This review is focused especially on medications such as renin-angiotensin-aldosterone system blockers or resveratrol, but even eating habits and lifestyle.

New Insights into Molecular Mechanisms of Chronic Kidney Disease.

Chronic kidney disease (CKD) is a major public health problem with a developing incidence and prevalence. As a consequence of the growing number of patients diagnosed with renal dysfunction leading to the development of CKD, it is particularly important to explain the mechanisms of its underlying causes. In our paper, we discuss the molecular mechanisms of the development and progression of CKD, focusing on oxidative stress, the role of the immune system, neutrophil gelatinase-associated lipocalin, and matrix metalloproteinases. Moreover, growing evidence shows the importance of the role of the gut-kidney axis in the maintenance of normal homeostasis and of the dysregulation of this axis in CKD. Further, we discuss the therapeutic potential and highlight the future research directions for the therapeutic targeting of CKD. However, additional investigation is crucial to improve our knowledge of CKD progression and, more importantly, accelerate basic research to improve our understanding of the mechanism of pathophysiology.

Cellular Mechanisms of Coronary Artery Spasm.

Coronary artery spasm (CAS) is a reversible phenomenon caused by spontaneous excessive vascular smooth muscle contractility and vascular wall hypertonicity, which results in partial or complete closure of the lumen of normal or atherosclerotic coronary arteries. The clinical picture of CAS includes chest discomfort which is similar in quality to that of stable effort angina. Mechanisms underlying the development of CAS are still unclear. CAS certainly is a multifactorial disease. In this review, we paid attention to the role of the main pathophysiologic mechanisms in CAS: endothelial dysfunction, chronic inflammation, oxidative stress, smooth muscle hypercontractility, atherosclerosis and thrombosis, and mutations leading to deficient aldehyde dehydrogenase 2 (ALDH2) activity. These findings might shed novel insight on the underlying mechanisms and identify potential diagnostic and therapeutic targets for cardiovascular diseases in the future.

Mineralocorticoid Receptor Antagonists-Use in Chronic Kidney Disease.

Mineralocorticoid receptor antagonists (MRA) are drugs with a potentially broad spectrum of action. They have been reported to have healing effects in many diseases, such as chronic heart failure, hypertension, or nephrotic syndrome. Numerous studies suggest that mineralocorticoid receptor activation is pathogenic and a progression factor of chronic kidney disease (CKD); however, results of studies on the use of MRA in the treatment of CKD are inconclusive. Current guidelines recommend against the use of MRA in patients with advanced CKD. Although, there is growing interest on their use in this population due to treatment benefits. In this review, we summarize studies which were purposed to evaluate the impact of MRA therapy on CKD patients. Despite many benefits of this treatment e.g., reducing cardiovascular mortality or alleviating proteinuria, steroidal MRA (such as spironolactone or eplerenone) have a low safety profile. They often lead to hyperkalemia complications which are dangerous in patients with CKD, and diabetic nephropathy, especially in hemodialysis patients. Studies on recently developed nonsteroidal MRA showed that they have fewer side effects. In our review, we discuss steroidal and nonsteroidal MRA treatment effects on the estimated glomerular filtration rate (eGFR), proteinuria, the cardiovascular system, and hyperkalemia in CKD patients. We present new content and recent publications in this field.