michigan hypertension core curriculum - State of Michigan

to elevated BP causes progressive glomerular damage. The damage and loss of additional glomeruli
further exacerbates the situation such that remaining glomeruli may promote even higher BP in order to
maintain waste clearance.
An additional issue that is well recognized by providers is the difficulty in controlling HTN in the
CKD population. In part, this difficulty is a result of trying to interrupt the maladaptive compensation of
kidneys to inadequate glomerular mass. Maintenance of HTN is occurs through multiple mechanisms.
A significant number, though not all, of these mechanisms are renin-angiotensin-aldosterone system
(RAAS)-related. Sympathetic nervous activity increases as glomerular filtration rate falls. Renin
production from the juxtaglomerular cells of the kidney is stimulated by sympathetic activity and
renal hypoperfusion. Renin, the rate-limiting enzyme in the synthesis of angiotensin II, converts
angiotensinogen to angiotensin I which is ultimately converted by angiotensin converting enzyme
(ACE) to the penultimate product of the RAAS system, angiotensin II. Angiotensin II is a potent
vasoconstrictor and in addition promotes sodium and water reabsorption from the renal proximal tubule.
Aldosterone production from the adrenal gland occurs in part from stimulation from angiotensin
II. Aldosterone promotes sodium chloride retention and as a result water, thus increasing vascular
volume and as a consequence, blood pressure. The RAAS is the most important intrinsic renal
contribution to HTN. In addition, the contribution of the RAAS to HTN as well as to the pathogenesis of
CKD makes clear why interruption with direct renin inhibitors, angiotensin converting enzyme inhibitors
and angiotensin receptor blockers have an important role in both lowering of BP as well as in the
preservation of kidney function control.
Kidney disease perpetuates HTN in part because of the diseases that cause CKD. Diabetes
mellitus is the leading cause of CKD in the U.S. and is responsible for over 40% of all end-stage
kidney disease (ESRD) cases. 1 The progressive macro and microvascular damage that occurs as
a consequence of glycemic and non-glycemic CVD risk factors (e.g., hypertension, dyslipidemia) in
persons with diabetes directly promotes HTN. Diabetes further contributes to HTN through direct
kidney injury in the form of diabetic nephrosclerosis. The loss of nephron mass contributes to HTN as
described previously. In addition, the proteinuria associated with diabetic nephropathy further injures
nephrons causing more kidney damage and further exacerbating the situation.
The second leading cause of advanced CKD and ESRD is essential HTN itself. 1 The
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