Is increased systemic vasoconstriction a stage in the perpetuating process of Chronic Kidney Disease (CKD)?

From the Guidelines

Increased systemic vasoconstriction plays a crucial role in the perpetuating process of Chronic Kidney Disease (CKD), as it raises blood pressure and reduces renal blood flow, thereby accelerating kidney damage. The relationship between hypertension and CKD is complex, with hypertension being both a cause and a consequence of kidney disease 1. As kidney function declines, the renin-angiotensin-aldosterone system (RAAS) becomes overactivated, leading to increased production of angiotensin II, a potent vasoconstrictor. This systemic vasoconstriction raises blood pressure and increases renal vascular resistance, which reduces renal blood flow and glomerular filtration rate.

The importance of managing hypertension in CKD patients is highlighted by the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline, which recommends a blood pressure target of <130/80 mm Hg for all patients with CKD 1. This is supported by the SPRINT study, which found that intensive blood pressure management provided benefits for reduction in the cardiovascular composite primary outcome and all-cause mortality in patients with CKD 1.

Key factors that contribute to vasoconstriction in CKD include:

• Overactivation of the RAAS system
• Sympathetic nervous system hyperactivity
• Endothelial dysfunction, which reduces nitric oxide production and increases endothelin-1
• Increased production of angiotensin II, a potent vasoconstrictor

The use of RAAS inhibitors, such as ACE inhibitors (e.g., lisinopril, enalapril) and ARBs (e.g., losartan, valsartan), is a cornerstone treatment for CKD, as they reduce vasoconstriction, lower blood pressure, and provide renoprotective effects. These medications decrease intraglomerular pressure and proteinuria, thereby slowing the progression of kidney disease 1. However, it is essential to avoid the combination of an ACE inhibitor and an ARB, as this approach has been associated with reported harms, including hyperkalemia and hypotension 1.

From the Research

Systemic Vasoconstriction in Chronic Kidney Disease (CKD)

• Increased systemic vasoconstriction is not directly mentioned as a stage in the perpetuating process of CKD in the provided studies 2, 3, 4, 5, 6.
• However, studies suggest that CKD is associated with increased sympathetic nerve activity (SNA) 5, which can contribute to hypertension and play a detrimental role in the progression of CKD.
• The renin-angiotensin system, which is involved in blood pressure regulation and kidney function, is also implicated in the development and progression of CKD 4, 6.
• Angiotensin receptor blockers (ARBs) have been shown to be effective in improving renal dysfunction and reducing proteinuria in patients with CKD 4.
• Other factors, such as inflammation, oxidative stress, and endothelial dysfunction, also contribute to the progression of CKD 2, 3, 6.

Mechanisms and Consequences

• The mechanisms leading to chronic sympathoexcitation in CKD are complex and multifactorial, and not completely understood 5.
• Increased SNA is associated with poor prognosis and increased cardiovascular morbidity and mortality independent of its effect on blood pressure 5.
• CKD is characterized by manifestations and symptoms involving systemic organs and apparatus, associated with elevated cardiovascular morbidity and mortality, bone disease, and other tissue involvement 3.
• The progression of CKD may not be linear, and new surrogate markers and omic-based technologies may allow for potential intervention and treatment in the earlier stages of CKD 6.