263CKD progresses, glomerular filtration rate (GFR) is reduced and, consequently, fil-
tered sodium and fluid load is reduced. It is important to realize that this net fall in
GFR is due to decreased GFR in some nephrons while hyperfiltration in other neph-
rons. This brings additional risk of glomerular damage and microalbuminuria in
remaining nephrons and additional decrease of GFR in time [ 27 ].
There is also an opinion that high salt intake directly blunts kidney autoregula-
tion, which exposes the glomerulus to higher filtration pressures [ 28 ]. Over time,
the high glomerular filtration pressure leads to glomerular sclerosis and nephron
loss. However, these compensatory mechanisms may be inadequate as CKD pro-
gresses and, hence, the resultant sodium retention and ECV expansion cause HT.
Second mechanism between salt intake and RHT may reside an amplification of
the effects of constrictors including angiotensin II or norepinephrine [ 26 , 29 ].
Third mechanism may be independent of BP; salt has unwanted effects on vessel
wall structure and endothelial function. Ying et al. have shown the involvement of
the fibrosis-promoting cytokine transforming growth factor-β (TGF-β) by salt.
Dietary salt intake, working through shearing stress at the endothelial level, acti-
vates the proline-enriched tyrosine kinase-2 pathway. Proline-enriched tyrosine
kinase-2, in turn, signals endothelial cells to produce TGF-β. By stimulating TGF-β
production, salt contributes to accelerated aging and fibrosis in the vessel wall [ 30 ].
It was also concluded that an excess of total body salt likely also contributes to arte-
rial stiffness, which is approximated by pulse pressure and known to be associated
with worsened kidney function [ 31 ].
Johnson and colleagues hypothesized a fourth mechanism regarding CKD,
hypertension, and salt. They have suggested that primary subclinical renal micro-
vascular disease leading to afferent arteriolopathy and tubulointerstitial disease may
be responsible for the development of HT [ 32 ]. Progressive tubulointerstitial dis-
ease will eventually result in microalbuminuria before the development of clinically
apparent impairment of glomerular filtration. Concurrent microvascular damage is
thought to result in renal vasoconstriction and subsequent local generation of angio-
tensin II. The resulting increased vascular resistance, reduced rate of ultrafiltration,
and decreased sodium excretion cause sodium retention, volume expansion, and
hypertension [ 33 ].
Thus by the light of aforementioned data one can say that BP in CKD patients is
salt sensitive and with decreasing renal function, the salt sensitivity of BP increases
[ 34 ]. The potential mechanisms related with increased salt and development of HT
in CKD are summarized in Table 16.1.
Indeed clinical observations have also confirmed the specific role of salt in HT in
CKD patients. For instance, salt-loading in CKD patients and healthy subjects over
several days results in a predictable expansion of ECV and an increased fractional
excretion of sodium; however, patients with CKD show an increase in arterial BP
concomitant with the increase in ECV, whereas healthy subjects have no significant
change in arterial BP [ 35 ]. It is also interesting to observe that the extent of ECV
expansion correlates with the severity of renal impairment and contributes to
approximately 5–10% of body weight even in the absence of peripheral edema [ 36 ].
16 Treatment of Hypertension in Light of the New Guidelines: Salt Intake