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Miscellaneous Other Non-humoral Factors
Mineral and Bone Disorders
The progression of CKD is associated with disorders of mineral metabolism (hyper-
phosphatemia and hypocalcemia), leading to the development of secondary hyper-
parathyroidism, which occurs even at early stages of CKD. Vascular stiffness is
induced by altered mineral metabolism in CKD patients. Secondary hyperparathy-
roidism may contribute to arterial stiffness and hypertension.
Hyperphosphatemia develops due to impaired renal phosphate excretion in
advanced CKD patients. Hyperphosphatemia may directly induce vascular injury
and indirectly stimulates osteoblastic differentiation of vascular smooth muscle
cells. Vascular calcification or excessive collagen accumulation can further stiffen
the arterial and/or arteriolar wall in patients with CKD. But decreased vascular com-
pliance because of vascular calcification has a more pronounced effect on systolic
pressure.
Fibroblast growth factor-23 (FGF-23), a hormone produced by osteoblasts, is
involved in the regulation of phosphate and vitamin D metabolism. FGF-23 level
rises in patients with CKD from early stages on. We still need to know more about
the influence of FGF-23 on the pathogenesis of hypertension.
Uric Acid
Uric acid is the main urinary metabolite of purines. Hyperuricemia seems to be a
cofactor in sodium-sensitive hypertension. It has been showed that circulating high
uric acid levels were associated with increased prevalence of hypertension [ 36 – 38 ].
Potential mechanisms to account for this association are the activation of intrarenal
RAAS, vascular smooth muscle cell proliferation, and impaired endothelial NO
productions [ 39 ]. But the role of hyperuricemia in CKD-related hypertension is still
a matter of controversy.
Oxidative Stress
Oxidative stress commonly accompanies both hypertension and CKD and is
believed to contribute in part to their pathogenesis [ 40 ]. Oxidative stress occurs
when generation of the reactive oxygen species (ROS) exceeds the natural antioxi-
dant capacity of the organism. It is well known that uremia increases ROS activity
and decreases antioxidant capacity. The exact mechanism through which oxidative
stress may raise blood pressure has not been fully elucidated. Oxygen radicals and
endogenous scavenging systems modulate vascular tone and function. ROS may
F. Turgut et al.