Resistant Hypertension in Chronic Kidney Disease

162

overactivity could be involved in CKD progression, such as facilitation of hyperten-
sion target organ damage, directly and/or mediated by angiotensin II [ 60 ]. Now we
know that sympathetic activation and CKD go hand in hand, starting early in CKD
evolution [ 61 ].
Mechanisms are far from elucidated, but now we do know that in CKD there is
first a deficit in the baroreflex afferent component and then a gradual impairment of
central control of renal sympathetic nerve activity and heart rate; both these earlier
and later components are associated with serious baroreflex dysfunction [ 62 ]. A
relevant study used the subtotal nephrectomy model and α2A-adrenoceptors knock-
out mice to investigate whether in renal failure the actual mechanism of increased
noradrenaline release from renal sympathetic nerve endings involves altered intrin-
sic synaptic autoregulation [ 63 ]; the study revealed that those presynaptic adreno-
ceptors are less efficient in inhibiting noradrenaline release in renal failure. On the
other side, it has been known for almost 40 years that reduced baroreflex sensitivity
could contribute to hypertension in patients with end-stage chronic glomerulone-
phritis [ 64 ].
Baroreflex activation (discussed in some detail in the previous sections) has
recently been shown to be effective in CKD with resistant hypertension, by decreas-
ing ABP and proteinuria and by stabilizing estimated glomerular filtration rate
(GFR) [ 65 ]. Baroreflex activation has also been shown to be a safe and effective
therapy in end-stage renal disease (ESRD) [ 66 ]. Several small-scale studies investi-
gated renal sympathetic denervation in CKD and, on purpose, the benefits of such
procedures regarding resistant hypertension in CKD and, to some extent, the mech-
anisms involved.
Sympathetic vasoconstrictor tone itself can be more important as hypertensive
mechanism than any “vascular amplifier effect,” as shown in the Lewis polycystic
kidney rat model of CKD [ 67 ]. It has been directly shown, by telemetry of ABP and
of renal sympathetic nerve activity, that the increase in the latter could be a major
hypertension mechanism in a rat model of genetic CKD [ 68 ].
Renal sympathetic denervation (by intravascular radiofrequency catheter), a safe
and efficient remedy in hypertension resistant to antihypertensive drugs, possibly
including hypertension in CKD [ 69 , 70 ], does not affect patient adherence to the
respective ongoing medication [ 71 ], while it was already known that renal
denervation is more efficient in patients with resistant hypertension who also have
impaired cardiac baroreflex sensitivity [ 72 ].

CKD

Na+ reabsorption RAAS

Resistant hypertension

Sympathetic outflow

Fig. 10.1 The key role of
sympathetic overactivation
in the frame of pathogenic
relations between chronic
kidney disease (CKD) and
hypertension

R. Iliescu and D.N. Şerban