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A reduced number of nephrons have been proposed as one of the factors contrib-
uting to the development of primary hypertension. Autopsy series from victims of
fatal accidents showed that hypertensive patients had fewer nephrons than matched
normotensive controls [ 11 ]. With a decline in nephron numbers, abnormalities of
sodium homeostasis are prominent, and prevalence of salt-sensitive hypertension
increases in CKD patients. However, the exact nature of renal defect or defects
responsible for inappropriate sodium excretion remains unclear.
Subtle renal defects associated with sodium excretion may underlie the patho-
physiology of hypertension in CKD. It has been shown that normotensive subjects
with family history of hypertension respond to salt loading with less natriuresis and
higher blood pressure than those with no family history [ 12 ].
It is also theorized that sodium may elevate blood pressure through direct vaso-
toxic effects such as increased inflammation, oxidative stress, and arterial stiffness
[ 13 , 14 ]. High dietary salt intake exacerbates hypertension in patients with CKD,
and dietary sodium restriction decreases extracellular volume and blood pressure in
this patient group [ 15 ]. Chronic forms of glomerulonephritis nearly always show a
mixture of volume-mediated and vasoconstrictor pathophysiology.
The Role of Volume Expansion
Rise in blood pressure is initially mediated by expansion of extracellular fluid vol-
ume, despite reduction in total peripheral vascular resistance. Renal salt and water
retention is sufficient to increase the extracellular fluid and blood volume.
The critical role of volume expansion in hypertension due to CKD is under-
scored by the effect of ultrafiltration or diuretics on blood pressure. Patients with
CKD have elevated extracellular fluid volume which can be corrected acutely with
the help of loop diuretics. Persistent diuretic use results in dynamic changes in
extracellular fluid volume that provides better blood pressure control in earlier
stages of CKD [ 16 ]. In patients with ESRD, the role of extracellular fluid volume
expansion is also apparent in the pathogenesis of hypertension. Inter-dialytic weight
gain is associated with inter-dialytic increase in ambulatory blood pressure. It is
reported that only a minority of patients undergoing better volume control with 8-h
thrice-weekly or short daily hemodialysis require antihypertensive medications for
blood pressure control in patients on maintenance hemodialysis [ 17 , 18 ]. Similarly,
better blood pressure control can be achieved by strict volume control in peritoneal
dialysis patients [ 19 ].
Positive sodium balance and hypervolemia are the dominant but not sole factor
in the pathogenesis of hypertension in CKD patients. Additional important volume-
independent factors regulating blood pressure may also contribute to CKD-related
hypertension. Some evidence suggests that there is an important sympathetic neural
component for pathogenesis of hypertension.
F. Turgut et al.