Hypertension and CKD

Outline
• Prevalence
• Hypertension effect on renal function
• BP control and progression in CKD
Prevalence
• The prevalence of hypertension in CKD is high and increases with the
severity of renal function ranging from 75% to 89% in advanced CKD
stages.
Hypertension Effect on Renal Function
• Mild to moderate hypertension causing renal injury is, as discussed
before, inconsistent across animal and human clinical studies
• Histological changes associated with this type of hypertension are
arteriolar hyalinosis*, medial hypertrophy**, and intimal fibrosis

(*)Type of arteriosclerosis, refers to thickening of the walls of arterioles by the deposits that appear as
homogeneous pink hyaline material in routine staining, not specific to hypertension and can be found in other
conditions such as diabetes and aging
(**) circumferential thickening of the tunica media of arteries that often results in narrowing of the vascular
lumen
• these changes lead to ischemic glomerulosclerosis demonstrated by the
collapse of capillary loops and wrinkling of the capillary basement, leading
to wall thickening.
• This ultimately results in glomerular tuft retraction and filling of the
Bowman space with collagen
• In addition, the tubules may show areas of atrophy and tubular lumen
dilatation as well as chronic interstitial inflammatory cells surrounding the
areas of tubular atrophy.
• Evidence suggests that impaired renal autoregulation results in the
transmission of systemic pressure to the renal microvasculature, leading to
renal microvasculature acute injury
BP Progression and Control in CKD
• Ultimately, the main factors that account for the presence and exacerbation of hypertension in
CKD include increased extracellular volume and increased vascular resistance
• The main mechanisms that contribute to the presence and exacerbation of these factors are
sympathetic nervous system overactivity and activation of the renin-angiotensin-aldosterone
system (RAAS), which result in arterial stiffness and impaired renal and water excretion
• Increased volume* and cardiac output are the first changes that begin even before any change in
BP manifests
• Hypertension develops once the vascular bed compliance can no longer compensate for the
increase in the blood volume

(*) related to the impaired salt and water excretion that occurs in CKD as a consequence of altered pressure natriuresis in the
presence of a decreased glomerular filtration rate (GFR) and the presence of angiotensin II resultant from RAAS activation
• Most of the patients with moderate to advanced CKD face a state of
volume expansion, which correlates with higher BP levels and worse
clinical outcomes
• These adverse outcomes are the result of not only hypertension but the
direct and independent effects of volume expansion and sodium load
• The overactivity of the sympathetic nervous system in CKD contributes
both to increased volume expansionand vascular resistance.
• Several stimuli identified for increased sympathetic activity in CKD (i.e.,
renal ischemia, hyperleptinemia, RAAS, uremic toxins, smoking, obesity,
hypercapnia, and decreased nitric oxide availability)
• The consequences of this hyperactive sympathetic system are
activation of the RAAS with increased release of renin and
angiotensin II, vasoconstriction of renal vasculature with arterial
smooth muscle and fibroblast proliferation, and salt and water
retention
• There is also evidence that sympathetic overactivity can result in
increased local inflammatory cytokines, which could additionally
potentiate the progression of CKD
• The 2014 Eighth Joint National Committee guidelines recommend a
goal BP for adults with hypertension and CKD of ≤140/90 mmHg
• Control:
• Therapeutic control
• Lifestyle modification
• Surgical intervention
• Therapeutic control:
• Considerable evidence from animal models of CKD that RAAS blockade using either
angiotensin-converting enzyme inhibitors (ACEIs ) or angiotensin receptor blockers
(ARBs) results in decreased glomerular pressure and consequently proteinuria,
protects against arterial wall thickening, prevents activation of profibrotic and
proinflammatory cytokines and macrophage recruitment. Human trials have
confirmed the protective effects of these agents in both diabetic and nondiabetic
individuals with CKD
• Direct renin inhibitor
• Aldosterone antagonist (not confirmed in CKD patient)
• Diuretics
• Calcium channel blocker
• Adrenergic blocker