135stimulate vascular contraction directly through decreasing local NO production or
modulate central SNS activation.
Drugs
Several drugs may contribute to hypertension in CKD patients (Table 8.1).
Calcineurin inhibitors (CNIs) (cyclosporine and tacrolimus) are routinely used to
prevent rejection after transplantation and occasionally to treat autoimmune dis-
ease. Hypertension induced by CNIs has been attributed to indirect vascular effects
(vasoconstriction, impaired vasodilatation) and sodium retention by increasing
endothelin-1, RAAS, and SNS activity and decreasing NO level [ 41 , 42 ]. Tacrolimus
appears to be less pro-hypertensive than cyclosporine. In addition to CNIs, gluco-
corticoids may also contribute to hypertension in kidney transplant recipients and
patients with renal parenchymal disease. Glucocorticoids lead to fluid retention by
their mineralocorticoid effect.
Erythropoiesis-stimulating agents (ESA) can worsen blood pressure control in
CKD patients. The mechanisms responsible for ESA-induced hypertension have
been attributed to increased blood viscosity, hypersensitivity to norepinephrine and
angiotensin II, impaired endothelial relaxation or direct vasoconstrictor effect,
increased cytosolic calcium, and increased blood serotonin or endothelin-1 levels
[ 43 ].
Finally, independent of the organ system playing a role in high blood pressure,
arterial hypertension may be considered a disease of vessels characterized by endo-
thelial dysfunction, vascular remodeling, increased stiffness, and reduced distensi-
bility [ 44 ]. It is clear that alterations in vascular function and structure are frequently
observed in CKD. Processes that can stiffen the arterial or arteriolar wall, such as
vascular calcification or excessive collagen accumulation, are both known to be
more active in patients with CKD and contribute to an increase in blood pressure.
In conclusion, it is clear that hypertension in CKD is multifactorial; however,
volume expansion by excessive salt intake and RAAS activation by several mecha-
nisms are predominant factors contributing to hypertension in patients with CKD.
References
- US Renal Data System USRDS 2010 Annual Data Report. Atlas of chronic kidney disease and
end-stage renal disease in the United States. Bethesda: National Institutes of Health, National
Institute of Diabetes and Digestive and Kidney Diseases; 2010. - Foley RN, Parfrey PS, Sarnak MJ. Clinical epidemiology of cardiovascular disease in chronic
renal disease. Am J Kidney Dis. 1998;32(5 Suppl 3):S112–9. - USRD 2009. Atlas of Chronic Kidney Disease in the United States. Am J Kidney Dis.
2010;55(Suppl 1):S1–420.
8 Pathophysiological Insights of Hypertension in Patients with Chronic Kidney Disease