Renal Hypertension
Shahram Taheri M.D.
Associated Prof.
IUMS
INTRODUCTION
• Hypertension is a frequent finding in both acute and
chronic kidney disease, particularly with glomerular or
vascular disorders.
• The pathogenesis and preferred treatment of
hypertension vary with the type of renal disease and
its duration.
PATHOGENESIS
• The pathogenesis of hypertension varies with the type
of disease (eg, glomerular versus vascular) and with
the duration of disease (acute versus chronic).
Acute glomerular disease
• Patients with acute glomerular disease, such as
poststreptococcal glomerulonephritis or membranous
nephropathy, tend to be volume expanded and
edematous due to sodium retention.
• As a result, the elevation in blood pressure is primarily
due to fluid overload, as evidenced by suppression of
the renin-angiotensin-aldosterone system and
enhanced release of atrial natriuretic peptide.
Acute glomerular disease
• Although these changes are most prominent with
severe disease, the incidence of hypertension is
increased even in patients with a normal serum
creatinine concentration.
• Both a familial predisposition to hypertension and
subclinical volume expansion are thought to be
important in this setting.
Acute glomerular disease
• Experimental studies of the nephrotic syndrome or
glomerulonephritis suggest that sodium retention in
these disorders is due to increased reabsorption in the
collecting tubules.
Acute vascular disease
• Hypertension is also common in acute vascular
diseases, such as vasculitis or scleroderma renal
crisis.
• In these settings, the elevation in blood pressure
results from ischemia-induced activation of the reninangiotensin system rather than volume expansion.
Acute vascular disease
• This difference in mechanism between glomerular and
vascular disease may be of diagnostic importance.
• As an example, a patient presenting with acute kidney
injury, hypertension, and red cells and red cell casts in
the urine sediment almost certainly has either
glomerulonephritis or vasculitis.
• The absence of edema in this setting would point
strongly toward a primary vascular disease.
Chronic kidney disease
• Hypertension is present in approximately 80 to 85
percent of patients with chronic kidney disease (CKD).
The prevalence of hypertension is elevated in patients
with kidney damage and a normal glomerular filtration
rate, and increases further as the glomerular filtration
rate falls.
Chronic kidney disease
• Data from the Modification of Diet in Renal Disease Study,
for example, showed that the prevalence of hypertension
rose progressively from 65 to 95 percent as the
glomerular filtration rate fell from 85 to 15 mL/min per 1.73
m2.
• As in patients without renal disease, the prevalence of
hypertension is also higher in patients with higher body
weight and in blacks.
Stage
GFR*
Description
Treatment stage
1
90+
Normal kidney function but urine findings Observation, control of blood
or structural abnormalities or genetic trait pressure. More on
point to kidney disease
management of Stages 1 and 2
CKD.
2
60-89
Mildly reduced kidney function, and other Observation, control of blood
findings (as for stage 1) point to kidney
pressure and risk factors.
disease
More on management of
Stages 1 and 2 CKD.
3A
3B
45-59
30-44
Moderately reduced kidney function
Observation, control of blood
pressure and risk factors.
More on management of Stage
3 CKD.
4
15-29
Severely reduced kidney function
Planning for endstage renal
failure. More on management
of Stages 4 and 5 CKD.
5
<15 or on Very severe, or endstage kidney failure
(sometimes call established renal
dialysis
failure)
Treatment choices. More on
management of Stages 4 and 5
CKD.
• There is a strong association between CKD and an
elevated blood pressure whereby each can cause or
aggravate the other.
• BP control is fundamental to the care of patients with
CKD and is relevant at all stages of CKD regardless of
the underlying cause.
• Hypertension is present in approximately 80 to 85
percent of patients with CKD.
• The prevalence of hypertension is elevated in patients
with kidney damage and a normal glomerular filtration
rate, and increases further as the glomerular filtration
rate falls.
• Data from the Modification of Diet in Renal Disease
Study, for example, showed that the prevalence of
hypertension rose progressively from 65 to 95 percent
as the glomerular filtration rate fell from 85 to 15
mL/min per 1.73 m2.
• As in patients without renal disease, the prevalence of
hypertension is also higher in patients with higher body
weight and in blacks.
• A variety of factors can contribute to the increased
prevalence of hypertension in patients with CKD:
– Sodium retention is generally of primary importance, even
though the degree of extracellular volume expansion may be
insufficient to induce edema.
– Increased activity of the renin-angiotensin system is often
responsible for at least part of the hypertension that persists
after the restoration of normovolemia, particularly in patients
with vascular disease since renal ischemia is a potent
stimulus of renin secretion.
– Regional ischemia induced by scarring may also play a role.
– Hypertension can be a causative (eg, hypertensive
nephrosclerosis) or contributory factor in the development of
kidney disease.
– Enhanced activity of the sympathetic nervous system. The
afferent signal may arise in part within the failing kidneys,
since it is not seen in patients who have undergone bilateral
nephrectomy.
– Secondary hyperparathyroidism raises the intracellular
calcium concentration, which can lead to vasoconstriction
and hypertension.
– Lowering parathyroid hormone secretion by the chronic
administration of an active vitamin D analog can reduce both
intracellular calcium and the systemic blood pressure.
– Treatment with erythropoietin, an effect that is in part related
to the degree of elevation in the hematocrit.
– Impaired nitric oxide synthesis and endothelium-mediated
vasodilatation has been demonstrated in patients with
uremia. Although the mechanisms are unclear, potential
explanations include reduced nitric oxide availability due to a
state of increased oxidative stress, or cofactor deficiencyinduced uncoupling of nitric oxide synthase.
TREATMENT OF HYPERTENSION IN
ACUTE GLOMERULAR OR
VASCULAR DISEASE
• Initial therapy with diuretics (particularly loop diuretics
in patients with reduced glomerular filtration rates) to
treat hypertension in patients with acute glomerular
disease and edema, since diuretics will also treat the
hypervolemia and associated edema.
• If the hypertension persists, angiotensin converting
enzyme (ACE) inhibitors may be effective, even in the
low renin hypertension often associated with acute
glomerulonephritis.
• This response may reflect activation of tissue reninangiotensin systems, such as that in the kidney,
vascular endothelium, and adrenal gland.
• ACE inhibitors as initial antihypertensive therapy in
patients with acute vascular diseases, since renal
ischemia leads to activation of the renin-angiotensin
system.
• Strong data support this approach in patients with
scleroderma renal crisis and prefer angiotensin
inhibition in polyarteritis nodosa and other vasculitides
as well.
TREATMENT OF HYPERTENSION IN
CKD
• Treatment of even mild hypertension is important in
patients with CKD to protect against both progressive
renal function loss and cardiovascular disease, the
incidence of which is increased with mild to moderate
CKD.
Goal blood pressure
• In patients with proteinuric CKD, usually defined as
greater than or equal to 500 mg/day or higher, the
blood pressure should be lowered to less than 130/80
mmHg.
• In patients with nonproteinuric CKD, defined as less
than 500 mg/day, the blood pressure should be
lowered to less than 140/90 mmHg.
LIFESTYLE MODIFICATION
• The impact of lifestyle-related factors on BP and the risk
of cardiovascular and other diseases have been well
documented.
• Encourage lifestyle modification in patients with CKD to
lower BP and improve long-term cardiovascular and other
outcomes:
• We recommend achieving or maintaining a healthy weight
(BMI 20 to 25).
Salt Restriction
• A relationship between average daily salt intake and BP
levels has long been recognized, leading to calls from
the World Health Organization (WHO) for salt intake to
be restricted to improve BP levels
(http://www.who.int/cardiovascular_diseases/guidelines/
Full%20text.pdf)
• We recommend lowering salt intake to o90mmol (<2 g)
per day of sodium (corresponding to 5 g of sodium
chloride), unless contraindicated.
Physical Exercise
• Increased physical exercise has been linked to a broad
range of positive health outcomes through a wide
variety of mechanisms.
• A clear inverse relationship between exercise and
average daily BP has been demonstrated by a large
volume of previous epidemiological data in the general
population, although exercise may lead to modest and
acute physiological increases in BP during the time of
the activity.
Physical Exercise
• We recommend undertaking an exercise program
compatible with cardiovascular health and tolerance,
aiming for at least 30 minutes 5 times per week.
Choice of antihypertensive therapy
• Attainment of goal blood pressure in patients with CKD
typically requires multidrug therapy.
• The choice of agent depends in part upon whether or
not the patients have proteinuria.
First-line therapy in proteinuric CKD
• Strong evidence favors the use of an ACE inhibitor or
angiotensin II receptor blocker (ARB) as first-line therapy in
patients with proteinuric CKD (protein excretion greater than
500 mg/day) because, in addition to lowering the blood
pressure, these drugs slow the rate of progression of CKD.
• Common side effects of angiotensin inhibition must be
considered including the acute reduction in glomerular
filtration rate and hyperkalemia that are more likely to occur
in patients with CKD.
First-line therapy in proteinuric CKD
• ACE-Is and ARBs should be used with caution or even
avoided in certain CKD subgroups, particularly in patients
with bilateral renal-artery stenosis or with intravascular
fluid depletion, because of the risk of a large reduction in
GFR.
• The normal capacity of the kidney to auto-regulate GFR in
the face of fluctuations in BP is impaired in CKD and
further compromised by the use of ACE-Is or ARBs.
Second- and third-line therapy in
proteinuric CKD
• In patients with CKD who have proteinuria
and edema, initial therapy usually consists of both an
angiotensin inhibitor for renal protection and a loop
diuretic for edema, which, by increasing renin release,
may also enhance the antihypertensive effect of the
angiotensin inhibitor.
• The use of a diuretic may also restore the
antiproteinuric effect of ACE inhibitor therapy in
patients without an adequate antiproteinuric response,
since volume expansion reduces angiotensin II
release and makes the blood pressure less dependent
upon angiotensin II.
• If further antihypertensive therapy is required, we
suggest a non-dihydropyridine calcium channel
blocker (eg, diltiazem or verapamil) since these drugs
also lower proteinuria.
• In contrast, dihydropyridines (eg, amlodipine) have
little or no effect on protein excretion.
• In patients with CKD who have proteinuria but not
edema, we suggest either a diuretic or a nondihydropyridine calcium channel blocker as secondline and then third-line therapy.
• Volume expansion, even in the absence of edema,
often plays a major role in hypertension associated
with CKD.
Antihypertensive therapy in
nonproteinuric CKD
• In patients with edema, initial therapy with a loop
diuretic. Once the edema is controlled, an angiotensin
inhibitor or a calcium channel blocker can be added in
either order if hypertension persists.
Antihypertensive therapy in
nonproteinuric CKD
• In patients without edema, start with an angiotensin
inhibitor, and then add a calcium channel blocker as
second-line therapy.
• If needed, we suggest adding a diuretic as third-line
therapy.
Fourth-line therapy with other agents
• Other antihypertensive drugs can be used as necessary
in patients with CKD who have resistant hypertension.
• An aldosterone antagonist
(spironolactone and eplerenone) is an effective fourthline agent for the treatment of resistant hypertension in
general and in patients with CKD.
• In addition to reducing blood pressure, aldosterone
antagonists also have antiproteinuric properties that
may be associated with a slower decline in renal
function.
• However, trials with patient-important outcomes are
not available.
• The efficacy of aldosterone antagonists was evaluated
in a study of 46 patients with a mean estimated
glomerular filtration rate (eGFR) of 57 mL/min per 1.73
m2 and hypertension that was not controlled with three
mechanistically complementary drugs, including a
diuretic and angiotensin inhibitor.
• The mean fall in systolic pressure induced by
aldosterone antagonists was 14.7 mmHg.
• The main adverse effects of aldosterone antagonists in
patients with CKD are a reduction in kidney function and
hyperkalemia.
• In the above study, 39 percent had a decline in estimated
glomerular filtration rate (eGFR) of 30 percent or more
when goal blood pressure was achieved and 17 percent
developed hyperkalemia occurred in 17 percent.
• Risk factors for hyperkalemia included a baseline eGFR
≤45 mL/min in patients with a serum potassium above 4.5
meq/L, and a fall in eGFR of more than 30 percent after
therapy.
Evaluation
Testing for renovascular hypertension
-Renovascular hypertension is the most common
correctable cause of secondary hypertension.
-Severe or refractory hypertension
-Including retinal hemorrhages or papilledema
- Bilateral renovascular disease may be present in
those patients who also have a plasma creatinine
above 1.5 mg/dL (132 µmol/L)
Renovascular hypertension
• Renovascular hypertension is likely the
most common correctable cause of
secondary hypertension. The incidence
of this condition varies with the clinical
setting. It probably occurs in less than 1
percent of patients with mild hypertension.
In comparison, between 10 and 45 percent
of white patients with severe or malignant
hypertension have renal artery stenosis
Renovascular hypertension
• Workup for renovascular
hypertension:
Additional testing for renovascular
disease is indicated only in patients in
whom the history is suggestive and in
whom a corrective procedure will be
performed if significant renal artery
stenosis is detected.
Renovascular hypertension
• The conditions to suspect to
renovascular or secondary
hypertension:
Severe or refractory hypertension,
including retinal hemorrhages or
papilledema
a plasma creatinine above 1.5 mg/dL
(132 µmol/L).
An acute rise in blood pressure over a
previously stable baseline
Suspicious to Renovascular hypertension
Proven age of onset before puberty or
above age 50.
An acute elevation in the plasma
creatinine concentration that is either
unexplained or occurs after the institution
of therapy with an angiotensin converting
enzyme inhibitor or angiotensin II receptor
blocker (in the absence of an excessive
reduction in blood pressure).
Suspicious to Renovascular
hypertension
Moderate to severe hypertension in a patient with diffuse
atherosclerosis or an incidentally discovered asymmetry
in renal disease. A unilateral small kidney ( 9 cm) has a
75 percent correlation with the presence of large vessel
occlusive disease.
Suspicious to Renovascular hypertension
 A systolic-diastolic abdominal bruit that lateralizes
to one side.
 This finding has a sensitivity of approximately 40
percent (and is therefore absent in many patients)
but has a specificity as high as 99 percent.
 Systolic bruits alone are more sensitive but less
specific.
 The patient should be supine, moderate pressure
should be placed on the diaphragm of the
stethoscope, and auscultation should be
performed in the epigastrium and all four
abdominal quadrants.
Suspicious to Renovascular
hypertension
Negative family history for hypertension.
Moderate to severe hypertension in patients with
recurrent episodes of acute (flash) pulmonary edema or
otherwise unexplained congestive heart failure.
Renovascular hypertension
• An intraarterial digital subtraction angiogram has
usually been the initial test when the history is
highly suggestive; however, spiral CT scanning
or 3D time-of-flight MR angiography provide a
minimally invasive and, in most cases, equally
accurate alternative to angiography.
• In addition, Doppler ultrasonography may help
predict the outcome of renovascularization
procedures.