michigan hypertension core curriculum - State of Michigan

[ACE inhibitors (ACEIs), angiotensin 2 receptor blockers (ARBs), direct aldosterone antagonists
(spironolactone, epleronone), and most recently direct renin inhibitors (aliskiren) are the primary
medications fulfilling these criteria. Non-dihyropyridine calcium channel blockers (NDHP CCBs)
reduce proteinuria though they have not been shown in prospective studies to provide the renal
protection observed with ACE inhibitors and ARBs. DHPCCBs preferentially dilate the efferent
glomerular arteriole and therefore can raise intraglomerular pressure – alikely explanation for
their inconsistent ability to lower proteinuria when used as monotherapy. However, when used
in conjunction with proven renoprotective RAAS blockade, these agents do not attenuate the
renoprotection of the RAAS blocker.
2. The ability of the kidney to maintain electrolyte and acid-base homeostasis is decreased, resulting
in an increased risk of treatment-related complications such as hyperkalemia and metabolic
acidosis when using RAAS inhibitors. In most patients with even advanced CKD, hyperkalemia
can be managed through dietary potassium restriction, and the use of furosemide (or other potent
diuretics used alone or in combination) and supplemental sodium bicarbonate. Occasionally, the
chronic use of low dose (2.5 – 5 g with meals) sodium polystyrene resin (Kayexalate®) may be
required.
3. In patients with certain etiologies of chronic kidney disease (e.g., renal artery stenosis or chronic
CHF) the maintenance of GFR there is dependent on angiotensin II, resulting in disproportionate
decreases in GFR during RAAS inhibitor therapy. In patients with late stage 4 or stage 5 CKD,
any preventable further decrease in GFR may be unacceptable because it may accelerate
the need for renal replacement therapy. Even patients with less severely decreased GFR are
already on the steep portion of the GFR v. serum creatinine plot, thereby demonstrating larger
increases in serum creatinine for a given further decrease in GFR than patients with normal GFR.
This frequently results in discontinuation of ACEIs, ARBs, and diuretics in patients with CKD
by physicians uncomfortable with any measurable elevation of serum creatinine or potassium
above normal. Nevertheless, this clinical decision must be balanced against prospective clinical
trial data showing a less steep decline in GFR over time with RAAS blockade in patients with
advanced CKD. Furthermore, in patients with advanced CKD, the predicable rise in creatinine that
occurs with either BP reductions and/or RAAS blockade will be exaggerated relative to the actual
loss of kidney function. In general, increases in serum creatinine of up to 30% are considered
acceptable. Larger increases in serum creatinine should prompt a search for volume depletion, or
possibly a search for bilateral renal artery stenosis.
4. The efficacy of some medications (e.g., thiazide diuretics) is decreased in patients with moderately
or severely decreased GFR. Other medications (e.g., loop diuretics) remain effective but requiring
proportionately higher dosing as GFR decreases. Thiazide diuretics are ineffective below an
estimated GFR < ~ 45 ml/min/1.73 m2 ; however, chlorthlidone, a thiazide-like diuretic, remains
effective at lower estimated GFR’s down to ~ the mid to low 30’s. Yet other medications (e.g.,
248 Hypertension Core Curriculum