Resistant Hypertension in Chronic Kidney Disease

129

The kidney acts as an excretory organ, a component in the sympathetic axis, and
a source of circulating constrictors and dilators. The traditional paradigm is that
hypertension in CKD is due to either an excess of intravascular volume (volume
dependent) or excessive activation of the renin-angiotensin-aldosterone system
(RAAS) in relation to the state of sodium/volume balance (renin-dependent hyper-
tension). However, numerous other factors of exogenous and endogenous nature
can influence blood pressure in patients with CKD, including enhanced activity of
the sympathetic nervous system, and factors influencing endothelial function.
Table 8.1 shows a list of proposed factors in the pathophysiology of hypertension
in CKD.

Role of Sodium Retention and Volume Overload

Sodium retention and consequent fluid overload have been well recognized in CKD-
related hypertension. The normal kidneys are exquisitely sensitive to blood pressure.
Acute rise in mean arterial pressure elicits a subtle increase in renal sodium and
fluid excretion. This “pressure natriuresis” also runs contrary and retains sodium
and fluid during decreases in blood pressure. The normal kidneys are also quite
effective in balancing volume status so much so that extracellular fluid and blood
volumes normally vary less than 10% with changes in salt intake. This delicate bal-
ance changes in a bad way with declining kidney function, and blood pressure often
increases with excessive salt intake.
The regulation of sodium excretion is a highly complex process and is not still
completely understood. There are so many regulatory pathways affecting sodium
excretion by the kidney including the RAAS, the mineralocorticoid receptor, the
endothelin system, and the nitric oxide (NO) [ 10 ]. The pathogenesis of hyperten-
sion is largely attributed to positive sodium balance in CKD patients. Many condi-
tions are associated with impaired salt excretion in CKD, including reduced renal
mass, the RAAS and sympathetic nervous system activation, and altered sodium
chloride handling in the distal nephron.

Table 8.1 Factors that may cause high blood pressure in chronic kidney disease

Well-known factors

Less-recognized

factors Plausible factors Drugs

Sodium and volume

excess

Mineral and bone

disorders

Sleep apnea ESAs

Activation of RAAS Endothelins Hyperuricemia CNIs

SNS hyperactivity Decreased NO Inflammatory

cytokines (i.e., TNF)

Steroids

Renovascular disease Oxidative stress Renalase NSAIDs
Arterial stiffness
RAAS renin-angiotensin-aldosterone system, SNS sympathetic nervous system, NO nitric oxide,
ESAs erythropoietin-stimulating agents, CNIs calcineurin inhibitors, NSAIDs nonsteroid anti-
inflammatory drugs

8 Pathophysiological Insights of Hypertension in Patients with Chronic Kidney Disease