This document discusses the management of hypertension in chronic kidney disease. It defines CKD and provides staging of CKD based on glomerular filtration rate. It discusses the high prevalence of hypertension in CKD patients and recommends targeting a systolic blood pressure under 120 mmHg through lifestyle modifications and pharmacological therapy including renin-angiotensin system inhibitors and calcium channel blockers. Resistant and refractory hypertension are also defined.

1. Management of Hypertension in
Chronic Kidney Disease (CKD)
Dr. S. M. Shamsuzzaman
MD (Nephrology)
Medical Officer
Department of Nephrology
Shaheed Suhrawady Medical College Hospital

2. Definition of CKD
CKD is defined as abnormalities of kidney structure or function,
present for >3 months, with implications for health.
Criteria for CKD (either of the following present for >3 months):
1. Markers of kidney damage-
1. Albuminuria (ACR>30mg/g, AER>30mg/24hrs)
2. Urine sediment abnormalities
3. Electrolyte and other abnormalities due to tubular
disorders
4. Abnormalities detected by histology
5. Structural abnormalities detected by imaging
6. History of kidney transplantation
2. Decreased GFR<60ml/min/1.73m2

3. Staging of CKD
GFR category GFR(ml/min/1.73
m2 )
Terms
G1 ≥90 Normal or high
G2 60-89 Mildly decreased
G3a 45-59 Mildly to moderately decreased
G3b 30-44 Moderately to severely decreased
G4 15-29 Severely decreased
G5 <15 Kidney failure

4. Albuminuria Categories
ACR (approximate
equivalent)
Category AER
(mg/24
hours)
(mg/mmol) (mg/g) Terms
A1 <30 <3 <30 Normaly or mildly
increased
A2 30-300 3-30 30-300 Moderatly increased.
microalbuminuria
A3 >300 >30 >300 Severely increased.
macroalbuminuria
Abbreviations: AER- albumin excretion rate; ACR- albumin-to-creatinine ratio.
Nephrotic syndrome (albumin excretion usually >2200 mg/24 hours.)

8. Epidemiology of Hypertension in
CKD
• HTN is extremely common in patients with CKD.
• 83% of 1795 patients screened for the Modifcation of Diet in
Renal Disease study were hypertensive and the frequency of
HTN increased with reducing GFR.

9. Diagnosis of HTN
• NICE thresholds for diagnosis of HTN are:
– Stage 1 HTN: clinic BP ≥140/≥90 mm Hg and subsequent
ABPM daytime mean or HBPM mean ≥135/≥85 mm Hg
– Stage 2 HTN: clinic BP ≥110/≥90 mm Hg and subsequent
ABPM daytime mean or HBPM mean ≥150/≥85 mm Hg
– Stage 3 HTN: clinic BP ≥180/≥110 mm Hg

10. Causes of Hypertension in CKD
• Impaired sodium excretion
– Expansion of ECF
volume
• Activation of RAS
– Direct vasoconstriction
– Sympathetic activation
• Sympathetic activation
– Direct vasoconstriction
– Stimulation of renin
release
• Imbalance in
prostaglandins or kinins
– Vasoconstriction
• Endothelin
– Direct vasoconstriction
– Renal injury
• Reduced nitric oxide
– Loss of vasodilator effect

11. Types of kidney disease causing
hypertension
• HTN is a frequent feature of all types of parenchymal kidney
disease.
• Normal or low BP in the presence of reduced GFR
suggests coincident heart failure but can occur in salt wasting
types of kidney disease (e.g. after relief of bilateral urinary
tract obstruction).

12. BP Phenotypes
Untreated patients
– Normotension
Normal office BP
Normal home or ambulatory BP
– White-coat HTN
High office BP
Normal home or ambulatory BP
– HTN
Normal office BP
High home or ambulatory BP
– Sustained HTN
High office BP
High home or ambulatory BP
Untreated patients
– Controlled Hypertension
office BP at goal
Home or ambulatory BP at goal
– WCE ( White Coat Effect)
office BP above-goal
Home or ambulatory BP at goal
– SUCH (Sustained Un Controlled
Hypertension )
office BP above-goal
Home or ambulatory BP above-goal
– MUCH ( Masked Un Controlled
Hypertension )
office BP at goal
Home or ambulatory BP above-goal

13. Resistant hypertension
• Resistant hypertension is defined as uncontrolled BP despite
the concurrent treatment with 3 antihypertensive drug classes,
inclusive of a long-acting calcium channel blocker, a blocker
of the renin–angiotensin–system and a diuretic, each one
administered at maximum or maximally tolerated doses.
• Patients whose BP is controlled with ≥4 antihypertensive
medications are also classified as having resistant
hypertension.
• Compared with the general population, the burden of resistant
hypertension is 2- to 3-fold higher among patients with
CKD.20

14. Refractory hypertension
• Refractory hypertension is the severe phenotype of complete
antihypertensive treatment failure defined in population-based
studies as above-goal BP when on ≥5 antihypertensive
medications, inclusive of a diuretic.
• The definition of refractory hypertension is not uniform, but
the 2017 AHA/ACC guideline defines refractory hypertension
as failure to control BP despite the administration of ≥5
antihypertensive medications of different classes, including a
long-acting thiazide-like diuretic, such as chlorothalidone, and
a mineralocorticoid receptor antagonist, such as spironolactone
• Among drug-treated hypertensives, refractory hypertension
was detected in only 0.6% (NHANES 1999–2014)

15. BLOOD PRESSURE
MEASUREMENT

16. Properly prepare the
patient
1. Have the patient relax, sitting in a chair (feet on floor, back
supported) for > 5 min
2. The patient should avoid caffeine, exercise, and smoking for
at least 30 min before measurement
3. Ensure patient has emptied his/her bladder
4. Neither the patient nor the observer should talk during the rest
period or during the measurement
5. Remove all clothing covering the location of cuff placement
6. Measurements made while the patient is sitting or lying on an
examining table do not fulfll these criteria

17. Use proper technique
for BP measurements
1. Use a BP measurement device that has been validated, and
ensure that the device is calibrated periodically
2. Support the patient’s arm (e.g., resting on a desk)
3. Position the middle of the cuff on the patient’s upper arm at
the level of the right atrium (the midpoint of the sternum)
4. Use the correct cuff size, such that the bladder encircles 80%
of the arm, and note if a larger- or smaller-than-normal cuff
size is used
5. Either the stethoscope diaphragm or bell may be used for
auscultatory readings

18. Take the proper measurements
1. At the frst visit, record BP in both arms. Use the arm that
gives the higher reading for subsequent readings
2. Separate repeated measurements by 1–2 min
3. For auscultatory determinations, use a palpated estimate of
radial pulse obliteration pressure to estimate SBP. Inflate the
cuff 20–30 mm Hg above this level for an auscultatory
determination of the BP level
4. For auscultatory readings, deflate the cuff pressure 2 mm Hg
per second, and listen for Korotkoff sounds

19. Properly document accurate BP
readings
1. Record SBP and DBP. If using the auscultatory technique,
record SBP and DBP as onset of the frst Korotkoff sound and
disappearance of all Korotkoff sounds, respectively, using the
nearest even number
2. Note the time of most recent BP medication taken before
measurements

20. Average the readings
• Use an average of ≥ 2 readings obtained on ≥ 2 occasions to
estimate the individual’s level of BP

21. BLOOD PRESSURE TARGETS

22. Recommended BP targets for
patients with diabetic or not-diabetic
CKD across guidelines

23. KDIGO 2021
• KDIGO 2021 suggests that adults with high BP and CKD be
treated with a target systolic blood pressure (SBP) of <120 mm
Hg, when tolerated, using standardized office BP measurement
.

24. Where not too strict
• CKD G4 and G5: For people with a lower GFR, there is less
certainly around the benefit of lower BP target and potential
risk of harm, compared to people with higher GFRs
• People with very low baseline DBP (e.g., <50 mm Hg),
particularly in the presence of coronary artery disease: In
theory, it is possible that intensive BP lowering will increase
the risk of myocardial infarction (MI) in this subgroup
because coronary perfusion depends on DBP.
• Older age

25. LIFESTYLE INTERVENTIONS
FOR LOWERING BLOOD
PRESSURE

26. Lifestyle interventions
Modifcation Recommendation SBP reduction
Weight Maintain normal body weight (BMI, 18.5–24.9 kg/m2) 5–20 mmHg/10 kg
Adoption of DASH
eating plan
Consume a diet rich in fruits, vegetables, low-fat dairy
products, with reduced content of saturated and total fat
8–14 mmHg
Reduced intake of
dietary sodium
Optimal goal is <1,500 mg/day, but aim for at least a 1,000
mg/day reduction in most adults consume <2 g (or <90
mmol)
5–6 mmHg
Enhanced intake of
dietary potassium
Aim for 3,500–5,000 mg/day, preferably by consumption
of a diet rich in potassium
4–5 mmHg
Physical activity Engage in regular aerobic physical activity such as brisk
walking (at least 90–150 min/week)
5–8 mmHg
Limitation
of alcohol
consumption
Limit daily consumption to no more than two drinks for
most men and to no more than one drink for women and
lighter weight persons
2.5–4 mmHg
Tobacco Total abstinence

27. KDIGO Recommendation (Sodium
intake)
• We suggest targeting a sodium intake <2 g of sodium per day
(or <90 mmol of sodium per day, or <5 g of sodium chloride
per day) in patients with high BP and CKD (2C).
• Practice Point 2.1.1: Dietary sodium restriction is usually not
appropriate for patients with sodium-wasting nephropathy.
• Practice Point 2.1.2: The Dietary Approaches to Stop
Hypertension (DASH)–type diet or use of salt substitutes that
are rich in potassium may not be appropriate for patients with
advanced CKD

28. KDIGO Recommendation (Physical
activity)
• We suggest that patients with high BP and CKD be advised to
undertake moderate intensity physical activity for a cumulative
duration of at least 150 minutes per week, or to a level
compatible with their cardiovascular and physical tolerance
Practice Point 2.2.1: Consider the cardiorespiratory fitness
status, physical limitations, cognitive function, and risk of falls
when deciding on the implementation and intensity of physical
activity interventions in individual patients.

29. PHARMACOLOGICAL
THERAPY

30. WHAT KDIGO 2021 SAYS

31. Treatment with antihypertensive
drugs including RAS inhibitors
• KDIGO recommends starting renin-angiotensin-system
inhibitors (RASi) (angiotensin-converting enzyme inhibitor
[ACEi] or angiotensin II receptor blocker [ARB]) for people
with high BP, CKD, and severely increased albuminuria (G1–
G4, A3) without diabetes (1B).
• KDIGO suggests starting RASi (ACEi or ARB) for people
with high BP, CKD, and moderately increased albuminuria
(G1–G4, A2) without diabetes (2C).
• KDIGO recommends starting RASi (ACEi or ARB) for people
with high BP, CKD, and moderately-to-severely increased
albuminuria (G1–G4, A2 and A3) with diabetes (1B)

32. Treatment with antihypertensive
drugs, including RAS inhibitors
• It may be reasonable to treat people with high BP, CKD, and
no albuminuria, with or without diabetes, with RASi (ACEi or
ARB).
• RASi (ACEi or ARB) should be administered using the
highest approved dose that is tolerated to achieve the benefits
• Changes in BP, serum creatinine, and serum potassium should
be checked within 2-4 weeks of initiation or increase in the
dose of a RASi, depending on the current GFR and serum
potassium.

33. Treatment with antihypertensive
drugs, including RAS inhibitors
• Hyperkalemia associated with use of RASi can often be
managed by measures to reduce the serum potassium levels
rather than decreasing the dose or stopping RASi.
• Continue ACEi or ARB therapy unless serum creatinine rises
by more than 30% within 4 weeks following initiation of
treatment or an increase in dose.
• Consider reducing the dose or discontinuing ACEi or ARB in
the setting of either symptomatic hypotension or uncontrolled
hyperkalemia despite medical treatment, or to reduce uremic
symptoms while treating kidney failure (estimated glomerular
filtration rate [eGFR] <15 ml/min per 1.73 m2).

34. ACEi and ARB combination
• KDIOGO recommends avoiding any combination of ACEi,
ARB, and direct renin inhibitor (DRI) therapy in patients with
CKD, with or without diabetes (1B).

35. RAS inhibitors
• ACE inhibitors
– Captopril, enalapril, lisinopril, perindopril, ramipril,
fosinopril, etc.
– block the conversion of angiotensin I to angiotensin II and
the degradation of bradykinin.
• Angiotensin receptor blockers (ARBs)
– Losartan, candesartan, irbesartan, valsartan, telmisartan
– act by competitively antagonizing the interaction between
angiotensin II and angiotensin receptors and were first
introduced as an alternative to ACE-Is in patients who had
an ACE-I induced cough

36. RAS inhibitors
• The most prominent BP-related effects of the blockade of
angiotensin II by ACE-Is or ARBs are as follows:
– Generalized arterial vasodilatation, resulting in lower BP.
– Vasodilatation of the efferent and afferent glomerular
arterioles, particularly the efferent, resulting in decreased
intra-glomerular pressure and hence reduction in both GFR
and urine albumin excretion. This is believed to result in
some degree of long-term renoprotection, at least in
patients with albuminuria.
– ACE-Is and ARBs may have other effects, including
inhibition of fibrosis and enhancement of vascular and
cardiac remodelling.

37. Indications for ACE-Is and ARBs
• Antihypertensive
• CKD patients with increased urinary albumin
excretion
– better kidney and cardiovascular outcomes.
• In non-CKD patients, these drugs are indicated for
– essential hypertension
– the treatment of heart failure
– soon after myocardial infarction,
– Stroke
– patients with high cardiovascular risk.

38. Caution
• Increased risk of hyperkalemia
• Hypotension: Acute fall in BP occur with ACEI when RAS is
activated e.g., overdiuresis, CHF, accelerated hypertension
• Cough is common (5–40%) with ACEIs.
• Angioneurotic edema is rare
• Pregnancy is contraindicated
• Rash and altered taste occur mainly with captopril

39. CALCIUM CHANNEL
BLOCKER

40. Calcium Channel blocker
• valuable BP-lowering agents in CKD patients
• major subclasses are
– the dihydropyridines (e.g., amlodipine, nifedipine and
lercanidipine)
– the non-dihydropyridine benzothiazepines (e.g., diltiazem)
– the phenylalkylamines (e.g., verapamil).
• Dihydropyridines tend to be more selective for vascular
smooth muscle (vasodilatation) with less action on the
myocardium.
• Non-dihydropyridines have direct effects on the myocardium,
including the sinoatrial and atrioventricular nodes and reduce
the heart rate and cardiac-muscle contraction.
•

41. Caution
• Flushing, tachycardia or headache occurs, especially with short
acting agents
• Dose dependent peripheral edema occurs with dihydropyridine
CCBs.
• Gum hypertrophy occurs with dihydropyridine CCBs
• Avoid use in systolic left ventricular impairment (especially
nondihydropyridine)
• Verapamil use is often accompanied by constipation.

42. CCB in CKD patients
• Most calcium channel blockers do not accumulate in patients
with impaired kidney function, with the exception of
nicardipine and nimodipine. Accumulation of these agents may
also be due to reduced blood flow to the liver in the elderly.
• Indications for calcium-channel blockers.
– treatment of hypertension, angina, and supra-ventricular
tachycardia.
– It is wise to avoid dihydropyridine calcium channel
blockers in CKD patients with already increased urinary
albumin excretion, particularly if there is not concomitant
use of an ACE-I or ARB.

43. DIURETICS

44. Diuretics
• Salt and water retention are major factors contributing to high
BP in CKD patients and to morbidity and mortality through
systemic or pulmonary edema. Thus, diuretics potentially have
an important role in the control of hypertension in this clinical
setting.

45. Thiazides and Thiazide-like diuretics
• Benzothiadiazines (thiazides): Hydrochlorothiazide,
benzthiazide, hydroflumethiazide, clopamide
• Thiazide like (related heterocyclics): Chlorthalidone,
metolazone, xipamide, indapamide
• Compete with both Na and Cl to block the Na Cl cotransporter
in the distal convoluted tubule (DCT)
• Caution:
– Hypokalemia (dose dependent)
– Impaired glucose tolerance (while used with a B blocker)
– Increase in low density lipoprotein, cholesterol and TG
– Increase in serum urate { Avoid, if history of gout.

46. Loop Diuretics
• Furosemide (also called frusemide), bumetanide, torsemide
and ethacrynic acid are the most commonly used loop
diuretics, with wide dose ranges and differing
pharmacodynamics
• They block the type 2 Na-K-2Cl cotransporter in the thick,
ascending limb of loop of Henle
• Loop diuretics are more potent natriuretics than thiazides, but
less effective BP lowering agents
• They have little place in the routine management of increased
BP, except in patients with congestive heart failure (CHF)
(with volume overload), renal impairment (with volume
overload) or some other edematous state (e.g., cirrhosis).

47. Dose considerations in CKD
patients.
• Although thiazides are excreted by the kidney, no dose
adjustment is recommended in patients with reduced GFR.
• As the GFR falls below about 30–50 ml/min/1.73 m2 , the
ability of thiazides to overcome fluid retention is diminished,
although their antihypertensive benefit may be preserved
• Most clinicians switch to a loop diuretic in patients with CKD
4, particularly if the BP is becoming resistant to therapy or
edema becomes a problem.

48. ALDOSTERONE ANTAGONISTS

49. Indications for Aldosterone
Antagonists.
• In patients with CKD, aldosterone antagonists
– decrease urine albumin excretion when added to ACE-I or
ARB therapy.
– Adjunct to other antihypertensives in resistant hypertension
– anti-albuminuric, anti-hypertensive, anti-fibrotic effects
reduce the rate of decline in kidney function in the long
term (Some author )
• With caution in CKD
– severe cardiac failure resistant to other therapies
– after acute myocardial infarction complicated by cardiac
failure.
– resistant hypertension

50. Caution considerations in CKD
patients
• Why
– Impaired renal excretion of native drug or active
metabolites of spironolactone and eplerenone
– increased risk of hyperkalemia
• Monitor
– S. Creatinine and Plasma Potassium
– during the introduction of aldosterone antagonists and
during intercurrent illnesses, particularly those associated
with a risk of GFR reduction, as occurs with dehydration.

51. BETA BLOCKERS

52. Beta Blockers
• Cardioselective Beta Blockers: Atenolol, betaxolol, bisoprolol,
metoprolol tartrate
• Noncardioselective Beta blockers : Nadolol, propranolol
• These agents are competitive inhibitors of catecholamines at β
adrenergic receptors.
• Useful if there is concomitant angina, post myocardial
infarction (MI), arrhythmias, or hyperdynamic circulation
• Reduce mortality and morbidity in patients with stable CHF

53. Dose considerations in CKD patients
• In patients with CKD, the accumulation of beta-blockers or
active metabolites could exacerbate concentration-dependent
side effects such as bradycardic arrhythmias.
• Such accumulation occurs with atenolol and bisoprolol, but not
carvedilol, propranolol, or metoprolol.

54. CAUTION IN SOME
COMBINATION

55. Caution in some combination
1. Dihydropyridines with other vasodilators problematic in
patients with CKD→ Fluid retention
2. Non-dihydropyridines such as verapamil and diltiazem with
beta-blockers can lead to severe bradycardia, particularly in
patients with advanced CKD if drugs such as atenolol and
bisoprolol, (that accumulate in CKD) are used.
3. ACE-Is and ARBs with Beta-blockers increase the risk of
hyperkalemia more in CKD
4. The combination of lipophilic beta-blockers (which cross the
blood–brain barrier; propranolol, metoprolol) with other
centrally acting drugs such as clonidine may lead to drowsiness
or confusion, particularly in the elderly.

56. Message
• Appropriate technique for BP measurement is must
• Lifestyle modification is very important tool for controlling
BP
• ACEi & ARBs are the mainstay treatment in Hypertension in
CKD
• Recent guidelines are focusing on intensified BP control with
more strict target BP
• We must be cautious in choosing Antihypertensive
combination
• BP control in CKD is a complex and dynamic job to do
sometimes which is unattainable

57. Reference
• KDIGO 2021 Clinical Practice Guideline for the Management of
Blood Pressure in Chronic Kidney Disease
• KDIGO 2012 Clinical Practice Guideline for the Management of
Blood Pressure in Chronic Kidney Disease
• Barratt, J. and Topham, P., 2009. Oxford Desk Reference:
Nephrology. Oxford University Press, USA.
• Practical Pearls in Hypertension / Narinder Pal Singh, BA
Muruganathan First Edition: 2018
• Pugh, D., Gallacher, P.J. and Dhaun, N., 2019. Management of
hypertension in chronic kidney disease. Drugs, 79, pp.365-379.
• Georgianos, P.I. and Agarwal, R., 2021. Hypertension in chronic
kidney disease (CKD): diagnosis, classification, and therapeutic
targets. American journal of hypertension, 34(4), pp.318-326.