From the Guidelines
Chronic kidney disease (CKD) causes secondary hypertension through a complex interplay of mechanisms, including impaired salt excretion, overactivation of the renin-angiotensin-aldosterone system, increased sympathetic nervous system activity, and altered medication efficacy, as highlighted in the 2018 American Heart Association scientific statement 1. The kidneys play a crucial role in regulating blood pressure by controlling fluid balance, sodium excretion, and producing hormones that affect blood vessels. In CKD, reduced kidney function leads to sodium and water retention, expanding blood volume and increasing blood pressure.
- The renin-angiotensin-aldosterone system (RAAS) is inappropriately activated, producing excess renin which triggers the formation of angiotensin II, a powerful vasoconstrictor that narrows blood vessels and raises blood pressure, as noted in the study by Carey et al. 1.
- CKD patients often experience increased sympathetic nervous system activity, which further constricts blood vessels and increases heart rate.
- Damaged kidneys also produce less nitric oxide (a vasodilator) and more endothelin (a vasoconstrictor), creating an imbalance that promotes hypertension. The study by Carey et al. 1 emphasizes the importance of controlling blood pressure in CKD management, typically requiring multiple antihypertensive medications, including ACE inhibitors or ARBs, which specifically target the RAAS system.
- The American Heart Association scientific statement 1 also highlights the need for special attention to be focused on appropriate dietary sodium restriction, as reduced salt intake may improve the efficacy of antihypertensive medications.
- The evidence suggests that CKD is both a cause and a complication of poorly controlled hypertension, and that treatment resistance in patients with CKD is related to increased sodium and fluid retention, and consequential intravascular volume expansion, as discussed in the study by Carey et al. 1.
From the Research
Pathophysiology of Secondary Hypertension in Chronic Kidney Disease
Chronic kidney disease (CKD) can lead to secondary hypertension due to a complex interplay of factors, including:
- Reduced number of functioning nephrons 2, 3, 4
- Sodium retention and volume expansion 2, 3, 4, 5
- Upregulation of the sympathetic nervous system 2, 3, 4, 5
- Hormonal factors such as upregulation of the renin-angiotensin-aldosterone system (RAAS) 2, 3, 4, 6, 5
- Endothelial dysfunction 2, 3, 4, 5
Role of the Renin-Angiotensin-Aldosterone System
The RAAS plays a crucial role in the pathophysiology of hypertension in CKD, promoting:
- Systemic and glomerular capillary hypertension 6
- Hemodynamic injury to the vascular endothelium and glomerulus 6
- Direct profibrotic and proinflammatory actions of angiotensin II and aldosterone 6
Consequences of Uncontrolled Hypertension
Uncontrolled hypertension can lead to: