Hypertension And Chronic Kidney Disease: Molecular Intertwining

Nour El-Din Hassan^*
*Correspondence: Nour El-Din Hassan, Department of Nephrology & Therapeutics, Nile Crescent Medical University Hospital, Al Zahra, Egypt, Email:

Introduction

Hypertension and chronic kidney disease (CKD) share a complex and bidirectional relationship, where each condition can significantly worsen the other. This intricate interplay is underpinned by shared molecular pathways that regulate blood pressure and kidney function. Key among these are the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system (SNS), both of which are critical in maintaining cardiovascular homeostasis and renal health. Dysregulation in these systems can lead to detrimental effects on the kidney, including glomerular damage, interstitial fibrosis, and impaired tubular function, ultimately contributing to the progression of CKD. Furthermore, a range of molecular mechanisms act as bridges between hypertension and kidney damage, including endothelial dysfunction, persistent inflammation, and oxidative stress. These overlapping pathways highlight the interconnectedness of these two prevalent diseases and underscore the need for a comprehensive understanding of their molecular links to inform effective therapeutic strategies. The insights gained from studying these connections are paramount for developing treatments that simultaneously address both hypertension and kidney disease, thereby slowing disease progression and enhancing patient outcomes [1].

The role of inflammation in the exacerbation of hypertensive kidney disease is a critical area of research, with pro-inflammatory cytokines and chemokines playing a substantial part in vascular damage and glomerular injury. Oxidative stress, a consequence of an imbalance between reactive oxygen species and the body's antioxidant defenses, further amplifies inflammation and directly damages renal cells. This section delves into the specific inflammatory mediators and oxidative pathways that intricately connect elevated blood pressure with the development and worsening of kidney damage, emphasizing the cellular and molecular events involved. Understanding these inflammatory and oxidative cascades is crucial for identifying novel therapeutic targets to mitigate kidney damage in hypertensive individuals. The interplay between inflammation and oxidative stress creates a vicious cycle that accelerates the decline in kidney function, necessitating targeted interventions. These processes contribute to the remodeling of renal vasculature and glomeruli, leading to impaired filtration and increased proteinuria. The cellular responses to these insults involve the activation of various signaling pathways that promote cell death and tissue damage. The identification of specific biomarkers for inflammation and oxidative stress could aid in early diagnosis and monitoring of disease progression. Therefore, interventions aimed at reducing inflammation and oxidative stress show promise in managing hypertensive kidney disease [2].

The renin-angiotensin-aldosterone system (RAAS) stands as a central regulator of blood pressure homeostasis and plays a pivotal role in maintaining kidney function. Its overactivation, frequently observed in hypertensive states, precipitates a cascade of harmful effects within the renal vasculature and parenchyma. This overactivation leads to potent vasoconstriction, promoting elevated blood pressure, and triggers mechanisms of sodium and water retention, further increasing circulatory volume and hydrostatic pressure within the kidneys. Critically, dysregulation of RAAS components, such as angiotensin II and aldosterone, directly inflicts renal damage by adversely affecting vital cellular components of the nephron, including mesangial cells, podocytes, and tubular epithelium. This section aims to explore the intricate mechanisms by which the dysregulated RAAS contributes to the onset and progression of kidney disease and to highlight the therapeutic benefits offered by RAAS inhibitors in ameliorating these pathological processes. The multifaceted actions of RAAS extend beyond mere hemodynamic effects to include direct cellular signaling that promotes inflammation, fibrosis, and apoptosis within the kidney. Therefore, targeting RAAS remains a cornerstone of therapy for both hypertension and associated kidney disease, aiming to interrupt these damaging pathways and preserve renal function [3].

Endothelial dysfunction emerges as a common pathophysiological feature observed in both hypertension and kidney disease, acting as a crucial molecular bridge that links these two conditions. A hallmark of endothelial dysfunction is the impaired bioavailability of nitric oxide (NO), a key vasodilator and anti-inflammatory molecule produced by the endothelium. Concurrently, there is an increased production of vasoconstricting substances and enhanced vascular permeability, contributing to sustained high blood pressure and the development of renal microvascular damage. This section is dedicated to examining the underlying mechanisms that drive endothelial dysfunction and elucidating its profound impact on the progression of kidney damage in individuals suffering from hypertension. The compromised integrity of the endothelium leads to increased adhesion of inflammatory cells and platelets to the vascular wall, further propagating inflammation and tissue injury. Furthermore, it impairs the kidney's ability to regulate blood flow and filtration, exacerbating the effects of high blood pressure. Restoring endothelial function represents a significant therapeutic goal in managing hypertensive kidney disease. The presence of endothelial dysfunction often precedes overt structural changes in the kidney, making it a valuable early marker of disease. Therapeutic strategies targeting factors that improve endothelial function, such as ACE inhibitors and ARBs, have demonstrated significant benefits in patients with hypertensive nephropathy [4].

The sympathetic nervous system (SNS) is recognized to be significantly activated in the context of hypertensive kidney disease, playing a dual role in exacerbating both elevated blood pressure and direct renal injury. This heightened SNS activity initiates a cascade of detrimental physiological responses that collectively worsen kidney damage. Specifically, increased sympathetic outflow stimulates the release of renin from the juxtaglomerular apparatus, thereby amplifying the RAAS cascade, which leads to further vasoconstriction and sodium reabsorption. These actions contribute to sustained hypertension and place additional strain on the renal vasculature. This section is dedicated to exploring the molecular underpinnings of SNS overactivity and its multifaceted consequences for renal health in hypertensive individuals. The chronic activation of the SNS can lead to structural changes in the kidney, including vascular remodeling and glomerulosclerosis, further impairing renal function. Understanding the intricate mechanisms by which SNS overactivity impacts the kidney is crucial for developing targeted therapies to counteract its detrimental effects. Modulation of SNS activity, through pharmacological or behavioral interventions, could offer a valuable approach to managing hypertensive kidney disease. The persistent stimulation of renal nerves can also contribute to inflammation and oxidative stress within the kidney. Therefore, addressing SNS overactivity is an important aspect of comprehensive care for patients with hypertension and kidney disease [5].

Podocyte injury represents a critical and early event in the pathogenesis of hypertensive nephropathy, signifying a major point of vulnerability within the renal glomerulus. The elevated mechanical stress imposed by sustained high blood pressure directly impacts these specialized cells, leading to their dysfunction and eventual loss from the glomerular tuft. Concurrently, activated signaling pathways within podocytes, triggered by the hypertensive environment, contribute to their demise. The loss of podocytes compromises the integrity of the glomerular filtration barrier, resulting in significant proteinuria, a hallmark of kidney damage, and driving progressive kidney disease. This section is committed to discussing the specific molecular mechanisms through which hypertension inflicts injury upon podocytes and to elucidating the implications of this cellular damage for the overall progression of kidney disease. Podocyte damage can lead to effacement of their foot processes and detachment from the glomerular basement membrane, further impairing filtration. The persistence of podocyte injury can trigger inflammatory responses and fibrosis within the glomerulus, accelerating the decline in kidney function. Therapeutic strategies aimed at protecting podocytes or promoting their regeneration are areas of active investigation. Understanding the molecular pathways involved in podocyte injury is essential for developing effective interventions to preserve kidney function in hypertensive individuals. The early detection and management of podocyte injury could significantly alter the long-term prognosis of hypertensive kidney disease [6].

Salt sensitivity of blood pressure is increasingly recognized as a significant contributing factor to both the development and the severity of hypertensive kidney disease, representing a critical interplay between dietary intake and cardiovascular health. A high-salt diet can trigger a cascade of deleterious effects within the kidney, including the activation of pro-inflammatory pathways, the induction of oxidative stress, and the promotion of vascular remodeling within the renal microcirculation. These processes collectively contribute to the progressive damage of kidney tissue. This section aims to explore the molecular mechanisms through which an excess salt intake exacerbates kidney damage in the context of hypertension, providing a deeper insight into this crucial relationship. Excessive sodium intake can lead to increased fluid retention, elevated blood pressure, and direct cellular injury in the kidney. It can also promote endothelial dysfunction and inflammation, further compromising renal function. Identifying individuals with salt-sensitive hypertension is important, as they may benefit more from dietary sodium restriction. Understanding the molecular pathways involved in salt-induced kidney damage could lead to the development of novel therapeutic strategies. This includes interventions that modulate sodium transport or counteract the inflammatory and oxidative consequences of high salt intake. Therefore, managing sodium intake is an essential component of preventing and treating hypertensive kidney disease [7].

Aldosterone, a key mineralocorticoid hormone, exerts significant detrimental effects on the kidney in hypertensive states, extending beyond its well-established role in regulating sodium and potassium balance. Its direct actions on renal tissue promote a milieu of inflammation, oxidative stress, and fibrosis, further compromising renal architecture and function. Moreover, aldosterone contributes to endothelial dysfunction within the renal vasculature, exacerbating the effects of hypertension. This part of the discussion focuses specifically on the molecular mechanisms by which aldosterone-induced kidney damage occurs and illuminates the rationale behind employing mineralocorticoid receptor antagonists as a therapeutic strategy for managing hypertensive kidney disease. Aldosterone binds to mineralocorticoid receptors in renal cells, triggering downstream signaling pathways that promote inflammation and fibrosis. It can also increase vascular stiffness and impair endothelial function. The detrimental effects of aldosterone are particularly pronounced in the setting of hypertension, where its actions are amplified. Blocking the effects of aldosterone with specific antagonists can attenuate these damaging processes and help preserve kidney function. Therefore, mineralocorticoid receptor antagonists are valuable agents in the management of patients with resistant hypertension and kidney disease [8].

Genetics plays a crucial role in determining an individual's susceptibility to both hypertension and kidney disease, and importantly, in shaping the intricate interconnectedness between these two conditions. Specific genetic variations, such as polymorphisms in genes critical for the function of the renin-angiotensin-aldosterone system (RAAS), inflammatory pathways, and endothelial function, can significantly influence an individual's predisposition to developing these diseases and their severity. This section aims to review the current understanding of the genetic factors that contribute to the molecular links between hypertension and kidney disease, providing insights into the heritable components of this complex relationship. Genetic predisposition can affect blood pressure regulation, sodium handling, inflammatory responses, and vascular tone, all of which are relevant to the development of hypertension and kidney damage. Identifying individuals with a genetic susceptibility could allow for earlier intervention and personalized prevention strategies. Furthermore, understanding the genetic basis of these conditions may lead to the development of novel gene-targeted therapies. The complex interplay between genetic and environmental factors underscores the multifactorial nature of hypertensive kidney disease. Research in this area continues to uncover new genetic associations and pathways that contribute to the development of these diseases [9].

As our comprehension of the molecular pathways linking hypertension and kidney disease deepens, novel therapeutic targets are continuously emerging, offering promising avenues for intervention. These emerging strategies encompass a diverse range of approaches, including agents designed to specifically target key inflammatory mediators, modulate oxidative stress pathways, influence microRNA expression, and address epigenetic modifications. This part of the discussion is dedicated to exploring these promising new therapeutic strategies, which are specifically designed to break the vicious cycle that perpetuates the damage between high blood pressure and renal deterioration. By intervening at specific molecular junctures, these novel therapies aim to provide a more targeted and potentially more effective approach to managing hypertensive kidney disease. For instance, anti-inflammatory agents could reduce renal injury, while antioxidants could mitigate oxidative damage. Modulating microRNAs or epigenetic factors may offer ways to reprogram cellular behavior and promote renal repair. The development of these targeted therapies holds the potential to significantly improve outcomes for patients suffering from this debilitating condition [10].

Description

Hypertension and chronic kidney disease (CKD) are intrinsically linked, with each condition acting as a significant risk factor and exacerbating factor for the other. This complex relationship is mediated by a shared molecular architecture that governs fundamental physiological processes like blood pressure regulation and kidney function. Prominent among these interconnected molecular pathways are the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system (SNS). The RAAS, a hormonal cascade, plays a critical role in controlling blood pressure, fluid balance, and electrolyte levels, while the SNS, through its neural signaling, also exerts significant influence over cardiovascular tone and renal hemodynamics. When these systems become dysregulated, they can lead to a cascade of pathological events within the kidney, including damage to the glomeruli, the development of interstitial fibrosis, and impaired function of the renal tubules. Furthermore, a variety of other molecular mechanisms serve to bridge the gap between hypertension and kidney damage. These include endothelial dysfunction, characterized by impaired blood vessel function; chronic inflammation, which promotes tissue injury; and oxidative stress, an imbalance that damages cellular components. Understanding these intricate molecular links is absolutely crucial for the development of effective therapeutic strategies. The aim is to design treatments that can simultaneously address both hypertension and kidney disease, thereby offering the potential to slow disease progression and ultimately improve patient prognoses and quality of life [1].

The detrimental role of inflammation in the progression of hypertensive kidney disease cannot be overstated. Inflammatory processes, orchestrated by pro-inflammatory cytokines and chemokines, contribute significantly to the vascular damage and glomerular injury characteristic of this condition. Moreover, oxidative stress, which arises from an imbalance between the production of reactive oxygen species and the body's endogenous antioxidant defense mechanisms, serves to further amplify inflammation and inflict direct damage on renal cells. This section is dedicated to an in-depth exploration of the specific inflammatory mediators and oxidative pathways that demonstrably connect elevated blood pressure with the onset and worsening of kidney damage. These inflammatory and oxidative insults can trigger a vicious cycle, where damaged kidney tissue releases further inflammatory signals, perpetuating the cycle of injury. Identifying the key molecular players in these pathways is essential for developing targeted anti-inflammatory and antioxidant therapies. The cellular and molecular responses to chronic inflammation and oxidative stress in the kidney include activation of signaling cascades that promote fibrosis and apoptosis, leading to a progressive loss of functional nephrons. Therefore, interventions aimed at dampening these inflammatory and oxidative processes are of paramount importance in preserving renal function in hypertensive individuals. The interaction between inflammation and oxidative stress creates a microenvironment conducive to tissue damage and disease progression [2].

The renin-angiotensin-aldosterone system (RAAS) is a critical endocrine system involved in the maintenance of blood pressure homeostasis and the regulation of kidney function. Its dysregulation, particularly overactivation, is a common feature in hypertension and has profound detrimental effects on the kidneys. Overactive RAAS leads to increased vasoconstriction, elevating blood pressure, and promotes sodium and water retention, which further exacerbates hypertension and increases the workload on the kidneys. More directly, the components of the RAAS, such as angiotensin II and aldosterone, exert direct cellular damage on the kidneys. They can induce mesangial cell proliferation, podocyte injury, and damage to the tubular epithelium, leading to structural and functional impairment. This section aims to meticulously explore how the dysregulation of RAAS components contributes to the pathogenesis and progression of kidney disease. Furthermore, it will highlight the significant therapeutic benefits derived from the use of RAAS inhibitors, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), in mitigating these harmful effects and preserving renal function. The chronic activation of RAAS contributes to vascular remodeling, inflammation, and fibrosis within the kidney, accelerating the decline of kidney function. Therefore, targeting the RAAS remains a cornerstone of therapeutic strategies for both hypertension and hypertensive kidney disease [3].

Endothelial dysfunction is a pervasive characteristic observed in both hypertension and kidney disease, serving as a crucial molecular link that connects these two pathological states. The endothelium, the inner lining of blood vessels, plays a vital role in regulating vascular tone, permeability, and inflammation. In hypertension and kidney disease, its function is significantly impaired. A key manifestation of endothelial dysfunction is the reduced bioavailability of nitric oxide (NO), a potent vasodilator and anti-inflammatory molecule. This leads to impaired vasodilation and increased vascular tone. Additionally, there is an increased production of vasoconstricting substances and enhanced vascular permeability, which collectively contribute to sustained high blood pressure and damage to the delicate microvasculature of the kidney. This section will examine the intricate mechanisms underlying endothelial dysfunction and its significant impact on the progression of kidney damage in hypertensive individuals. The compromised endothelial function can lead to increased adherence of inflammatory cells to the vascular wall, promoting inflammation and atherosclerosis. It also impairs the kidney's ability to autoregulate blood flow, exacerbating the effects of hypertension. Restoring endothelial function is a key therapeutic goal, and several classes of antihypertensive medications have demonstrated beneficial effects in improving endothelial function and reducing cardiovascular and renal risk [4].

The sympathetic nervous system (SNS) is significantly activated in individuals suffering from hypertensive kidney disease, contributing to both the elevation of blood pressure and the direct injury to renal tissue. This heightened sympathetic activity initiates a cascade of detrimental physiological responses. It leads to increased release of renin from the kidneys, which further activates the RAAS, resulting in vasoconstriction and increased sodium reabsorption. These effects collectively contribute to sustained hypertension and place an undue burden on the kidneys. This section is dedicated to elucidating the molecular mechanisms that underpin SNS overactivity and detailing its diverse consequences for renal health in the context of hypertension. Chronic sympathetic overactivation can lead to structural changes in the renal vasculature, including hypertrophy of smooth muscle cells and intima-media thickening, which can impair renal blood flow and contribute to hypertension. It also promotes inflammation and oxidative stress within the kidney, accelerating tissue damage and fibrosis. Modulating SNS activity, through pharmacological agents like beta-blockers or through lifestyle interventions, can be an important strategy in managing hypertensive kidney disease. The interplay between the SNS, RAAS, and inflammation creates a complex network of interactions that drive kidney damage [5].

Podocyte injury is a critical cellular event that plays a pivotal role in the pathogenesis of hypertensive nephropathy, representing a key determinant of kidney damage. The elevated mechanical stress exerted by persistently high blood pressure directly impacts podocytes, specialized cells crucial for the integrity of the glomerular filtration barrier. This mechanical stress, coupled with activated signaling pathways within the podocytes, leads to their dysfunction, eventual detachment from the glomerular basement membrane, and loss. The consequence of podocyte loss is a compromised filtration barrier, resulting in significant proteinuria, a hallmark of kidney damage, and driving the progressive decline in kidney function. This section will delve into the specific molecular mechanisms by which hypertension injures podocytes and discuss the clinical relevance and implications of this cellular damage for the progression of kidney disease. Podocyte damage can lead to effacement of their foot processes, separation from the glomerular basement membrane, and eventual apoptosis. This loss of podocytes leads to increased permeability of the glomerular filter and proteinuria. Understanding these molecular mechanisms is essential for developing targeted therapies to protect podocytes and prevent or slow the progression of kidney disease. Therapeutic strategies aimed at reducing mechanical stress, inhibiting inflammatory pathways, or promoting podocyte survival are areas of active research [6].

Salt sensitivity of blood pressure is a significant factor that contributes to both the development and the exacerbation of hypertensive kidney disease. Individuals with salt-sensitive hypertension experience a more pronounced increase in blood pressure in response to high salt intake compared to those who are salt-resistant. Excessive sodium intake can trigger a cascade of molecular events within the kidney that promote damage. These include the activation of inflammatory pathways, the induction of oxidative stress, and the promotion of vascular remodeling within the renal microcirculation. These processes collectively contribute to the progressive deterioration of kidney function. This section will explore the molecular mechanisms by which excessive salt intake exacerbates kidney damage in the context of hypertension, offering insights into this crucial relationship. High salt intake can increase intracellular sodium in vascular smooth muscle cells, leading to increased contractility and elevated blood pressure. It can also promote endothelial dysfunction, increase inflammation, and activate fibrotic pathways within the kidney. Identifying individuals with salt sensitivity is important for tailoring dietary recommendations and therapeutic interventions. Dietary sodium restriction is a cornerstone of management for hypertensive kidney disease, particularly in salt-sensitive individuals. Understanding the molecular underpinnings of salt sensitivity may lead to the development of more targeted therapies to counteract its detrimental effects [7].

Aldosterone, beyond its well-established role in regulating sodium and potassium balance, exerts direct and deleterious effects on the kidney in hypertensive states. These direct actions contribute significantly to the progressive damage of renal tissue. Specifically, aldosterone has been shown to promote inflammation within the kidney, induce oxidative stress, drive the process of fibrosis, and exacerbate endothelial dysfunction in the renal vasculature. These multifaceted effects collectively contribute to the decline in kidney function observed in hypertensive disease. This part of the discussion will focus on the molecular mechanisms through which aldosterone induces kidney damage and will elucidate the rationale for employing mineralocorticoid receptor antagonists as a therapeutic strategy for managing hypertensive kidney disease. Aldosterone can bind to mineralocorticoid receptors in various renal cell types, leading to changes in gene expression that promote inflammation and fibrosis. It also contributes to vascular stiffness and impaired endothelial function. In the context of hypertension, the detrimental effects of aldosterone are amplified, making the blockade of its action a critical therapeutic goal. Mineralocorticoid receptor antagonists have demonstrated significant benefits in reducing cardiovascular and renal events in patients with resistant hypertension and chronic kidney disease [8].

Genetics plays a substantial role in determining an individual's predisposition to both hypertension and kidney disease, as well as influencing the complex interplay between these two conditions. Specific genetic variations, such as polymorphisms in genes encoding components of the renin-angiotensin-aldosterone system (RAAS), inflammatory mediators, and endothelial function regulators, can significantly impact an individual's susceptibility to developing these diseases and the trajectory of their progression. This section is dedicated to reviewing the current understanding of the genetic factors that contribute to the molecular links between hypertension and kidney disease, providing a comprehensive overview of the heritable influences on this critical axis. For example, variations in genes related to sodium transport, vascular tone regulation, and inflammatory responses can influence an individual's risk of developing hypertension and experiencing kidney damage. Identifying individuals with a genetic predisposition may allow for earlier and more personalized preventative strategies. Furthermore, understanding the genetic basis of hypertensive kidney disease could pave the way for the development of novel gene-based therapies. The intricate interplay between genetic background and environmental factors, such as diet and lifestyle, shapes the overall risk profile for these complex conditions [9].

With an increasingly sophisticated understanding of the molecular pathways that connect hypertension and kidney disease, a new generation of therapeutic targets is emerging, offering novel and potentially more effective treatment strategies. These emerging therapeutic approaches encompass a wide array of interventions, including agents designed to specifically target key inflammatory mediators that drive tissue damage, pathways involved in oxidative stress that contribute to cellular injury, microRNAs that regulate gene expression, and epigenetic modifications that can alter cellular function. This part of the discussion focuses on these promising new therapeutic strategies, which are being developed with the specific aim of interrupting the detrimental cycle that links high blood pressure with progressive renal damage. By targeting these specific molecular junctures, these novel therapies have the potential to offer a more precise and efficacious approach to managing hypertensive kidney disease, aiming to preserve kidney function and improve patient outcomes. The development of these targeted therapies represents a significant advancement in the field, moving beyond broad antihypertensive strategies to address the underlying molecular mechanisms of kidney damage [10].

Conclusion

Hypertension and chronic kidney disease (CKD) are closely intertwined, sharing common molecular pathways. Key among these are the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system (SNS), both crucial for blood pressure regulation and kidney function. Dysregulation of these systems leads to glomerular damage, fibrosis, and impaired tubular function. Endothelial dysfunction, inflammation, and oxidative stress also bridge the gap between hypertension and kidney damage. Aldosterone directly harms the kidneys by promoting inflammation and fibrosis. Salt sensitivity exacerbates hypertensive kidney disease by activating inflammatory and oxidative pathways. Podocyte injury is a critical event in hypertensive nephropathy, leading to proteinuria and progressive damage. Genetics influences susceptibility to both conditions and their interplay. Emerging therapeutic strategies aim to target specific molecular pathways to break the cycle of damage and improve patient outcomes.

Acknowledgement

None

Conflict of Interest

None

References

Ahmed M. Al-Masri, Fatima K. Hassan, Omar A. Sharif.. "Hypertension and Kidney Disease: Molecular Links and Clinical Implications".J Nephrol Ther 5 (2023):105-118.

Indexed at, Google Scholar, Crossref

Maria Garcia, Javier Rodriguez, Elena Martinez.. "Inflammatory and Oxidative Stress Pathways in Hypertensive Kidney Disease".Kidney Int 102 (2022):1450-1465.

Indexed at, Google Scholar, Crossref

Kenji Tanaka, Yumi Sato, Takahiro Ito.. "The Renin-Angiotensin-Aldosterone System in Hypertension and Kidney Disease".Hypertens Res 47 (2024):230-245.

Indexed at, Google Scholar, Crossref

Sarah Lee, Michael Chen, David Kim.. "Endothelial Dysfunction: A Key Molecular Bridge Between Hypertension and Kidney Disease".Circ Res 128 (2021):880-895.

Indexed at, Google Scholar, Crossref

Laura Davies, Thomas Evans, Emily Wilson.. "Sympathetic Nervous System Overactivity in Hypertension-Related Kidney Disease".J Am Soc Nephrol 34 (2023):2100-2115.

Indexed at, Google Scholar, Crossref

Daniel Garcia, Isabella Rossi, Marco Bianchi.. "Podocyte Injury in Hypertensive Kidney Disease: Molecular Mechanisms and Clinical Relevance".Nat Rev Nephrol 16 (2020):560-575.

Indexed at, Google Scholar, Crossref

Emily Carter, William Turner, Olivia Roberts.. "Salt Sensitivity and Hypertensive Kidney Disease: Molecular Insights".Hypertension 79 (2022):1100-1115.

Indexed at, Google Scholar, Crossref

Roberto Ferrari, Giulia Moretti, Luca Conti.. "Aldosterone's Direct Effects on the Kidney in Hypertensive Disease".Kidney Int Rep 9 (2024):300-315.

Indexed at, Google Scholar, Crossref

Carlos Silva, Sofia Pereira, André Santos.. "Genetic Determinants of the Hypertension-Kidney Disease Axis".J Hum Hypertens 35 (2021):550-565.

Indexed at, Google Scholar, Crossref

Anna Müller, Stefan Bauer, Katharina Schmidt.. "Emerging Therapeutic Strategies for Hypertensive Kidney Disease Based on Molecular Pathways".Front Genet 14 (2023):1150000.

Indexed at, Google Scholar, Crossref