Why CKD Causes Hypertension
CKD causes hypertension primarily through sodium and water retention with extracellular volume expansion, which occurs because the diseased kidneys cannot adequately excrete sodium, leading to a vicious cycle where approximately 85% of CKD patients develop hypertension. 1
Primary Mechanism: Volume Expansion
- Impaired sodium excretion is the fundamental defect in CKD that drives hypertension, as reduced functioning nephron mass cannot handle normal sodium loads, resulting in progressive fluid accumulation in the extracellular compartment 1
- The relationship between volume and blood pressure may be sigmoidal rather than linear—blood pressure remains controlled until physiological autoregulation can no longer compensate for the fluid excess, then rises sharply 2
- Sodium directly disrupts normal autoregulation of glomerular filtration rate (GFR), exposing remaining glomeruli to inappropriately high systemic pressures and accelerating further kidney damage 1
Secondary Pathophysiological Mechanisms
Renin-Angiotensin-Aldosterone System (RAAS) Activation
- When functioning kidney mass declines, surviving glomeruli experience increased hemodynamic stress with activation of local RAAS, causing efferent arteriolar vasoconstriction more than afferent arteriolar dilation 1
- This maladaptive response increases single nephron GFR to maintain total GFR but transmits elevated systemic pressure directly into the glomerulus, perpetuating injury 1
- RAAS activation amplifies sodium retention and vasoconstriction beyond the primary volume effect 3
Sympathetic Nervous System Overactivity
- CKD patients demonstrate excessive sympathetic activation that contributes independently to hypertension through increased peripheral vascular resistance 4, 5
- This mechanism becomes particularly important in treatment-resistant hypertension in CKD 6
Endothelial Dysfunction and Vascular Changes
- Salt-related reduction in nitric oxide formation impairs vasodilation in CKD patients 2
- Arterial stiffness from arteriosclerosis limits vascular compliance, making blood pressure more sensitive to volume changes 2
- Structural arterial remodeling and decreased availability of endothelium-derived vasodilators contribute to sustained hypertension 6
The Bidirectional Relationship
- Hypertension both results from and accelerates CKD progression—this creates a self-perpetuating cycle where elevated blood pressure causes further nephron loss, which worsens volume retention and raises blood pressure further 7
- Disordered autoregulation of GFR occurs in CKD, allowing systemic blood pressure to be transmitted directly to the glomerulus rather than being buffered by normal afferent arteriolar constriction 1
- Proteinuria, which is common in CKD, further elevates blood pressure and activates cellular injury pathways promoting glomerulosclerosis 1
Clinical Implications
- Approximately 85% of CKD patients have hypertension, with prevalence increasing as kidney function declines—reaching 86% in advanced CKD cohorts 1
- Patients with proteinuric CKD have higher blood pressure than those with non-proteinuric CKD and show attenuated response to antihypertensive therapy 1
- Treatment resistance is common in CKD, with less than 15% achieving blood pressure control to 130/80 mmHg despite using an average of 3 different antihypertensive agents 1
Key Pitfalls to Avoid
- Do not assume hypertension in CKD is purely volume-mediated—while sodium and water retention is the primary mechanism, multiple overlapping pathways (RAAS, sympathetic overactivity, endothelial dysfunction) contribute and require comprehensive treatment 4, 5
- Recognize that conventional dialysis time may be too short for adequate ultrafiltration in some patients, and accelerated ultrafiltration can paradoxically worsen hypertension by triggering hypotension requiring saline administration 2
- In dialysis patients specifically, inadequate achievement of dry weight is a major contributor that must be addressed before escalating antihypertensive medications 2