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A STEPWISE APPROACH

TO BLOOD PRESSURE
MANAGEMENT IN CKD
PATIENTS
LEILANI ROSALIND CARAGOS-MERIN, MD
OUTLINE

• EPIDEMIOLOGY OF HYPERTENSION IN CKD


• PATHOPHYSIOLOGY OF HYPERTENSION IN CKD
• BLOOD PRESSURE THRESHOLD AND TARGETS
• DIAGNOSIS
• MANAGEMENT
CLINICAL SCENARIO
AL, 48 YEAR OLD FEMALE

• CC: Elevated BP • Non- smoker , Non- Alcoholic beverage


• Type 2 diabetes mellitus for more than 10 drinker ,No history of Ilicit drug use
years • No food and drug allergies
• Glipizide 10mg/tab OD

• Hypertensive for 1 year • Family History : Hypertension, DM2


• Lisinopril 10mg/tab OD
• Hydroclorothiazide 25 mg/tab OD
CLINICAL SCENARIO

• HPI
• Patient has been having increased blood pressure readings at home for 2 weeks
• BP: 150-160/ 90-100 mmHg
• No dizziness, no vomiting, no blurring of vision
• No change in urinary and bowel habits
• Referred by primary care physician due to increasing BP and a drop of eGFR to 35
ml/min /1.73m2 from 60ml/min/1.73 m2 last year
• and a urine spot protein to creatinine ratio of 30 mg/g
• Physical examination
• BP 170/100 mmHg HR: 70bpm RR: 20
• BMI 27.2kg/m2
• C/L : Equal chest expansion, clear breath sounds
• CVS: DHS , normal rate, regular rhythm
• Abdomen: Flat, normoactive bowel sounds, soft, nontender
• Ext: grade 1 bipedal edema
CLINICAL SCENARIO

Total Serum 180mg/dL Hgb 13.9


Cholesterol
HDL 58mg/dL Hct 40.4
LDL 93mg/dL WBC 6.2
Na 134 mEq/L Platelet 130
K 4.2 mEq/L Neutrophils 54
Cl 99mEq/L Lymphocytes 32
CO2 24 mEq/L Monocytes 9
FBS 225mg/dL Eosinophils 4.7
Ca 9.5mg/dL Basophils 0.3
Hba1c 6.7%
Crea 1.7 (eGFR 35)
CLINICAL QUESTIONS

• At what BP level should BP lowering agents be introduced in CKD patients?


• What BP levels should be aimed for?
• What is the stepwise approach for BP management in CKD patients?
EPIDEMIOLOGY OF HYPERTENSION IN CKD

• Prevalence: 60-90% , depending on the stage of CKD and the cause


• Uncontrolled hypertension is also associated with higher risk for cardiovascular (CV)
morbidity and mortality

Ku et al. Hypertension in CKD: Core Curriculum 2019. AJKD. Doi: 10.1053/j.ajkd.2018.12.044


PATHOPHYSIOLOGY

Ku et al. Hypertension in CKD: Core Curriculum 2019. AJKD. Doi: 10.1053/j.ajkd.2018.12.044


PATHOPHYSIOLOGY

• Factors related to CKD complications:


• Erythropoietin and erythropoiesis-stimulating agents
• Secondary hyperparathyroidism
• Vascular calcification  isolated systolic hypertension
• Uremia

• Medication Non-adherence
DIAGNOSIS

• Accurate BP measurement is critical to the diagnosis and management of CKD


• 24-H Ambulatory BP monitoring (ABP) - preferred
• Office BP monitoring
• Home BP monitoring

• BP measurements in all 4 extremities

Ku et al. Hypertension in CKD: Core Curriculum 2019. AJKD. Doi: 10.1053/j.ajkd.2018.12.044


TARGET BLOOD PRESSURE GOALS

CKD ND CKD ND CKD ND CKD ND CKD ND Renal


NON DM NON DM DM DM ELDERLY Transplant
No proteinuria No Proteinuria
proteinuria proteinuria

KDIGO ≤140/≤90 ≤130/≤80 ≤140/≤90 ≤130/≤80 individualize ≤130/≤80


(2012)
NICE <140/<90 <130/<80 <140/<80 <130/<80 Under 80
(2016) ≤140/≤90
Over 80
≤150/≤90
ACC/AHA <130/<80 <130/<80 <130/<80 <130/<80 >65 years; <130/80
(2017) ambulatory
SBP <130/80
ESC/ESH <140/90 65-80 years
(2018) SBP 140-150
JNC -8 <140/90 <140/90 <140/90 <140/90 <150/90
NONPHARMACOLOGIC THERAPY

• Dietary and Behavioral Modification


• DASH diet
• Increasing potassium intake to 3 to 4 g/d (difficult for CKD4 and5)
• Reducing sodium intake to <1.5g/day
• Limiting Alcohol intake
• Weight loss
• CPAP for patients with sleep apnea
• 90 to 150 minutes of aerobic exercise per week
• Avoid NSAIDS

Ku et al. Hypertension in CKD: Core Curriculum 2019. AJKD. Doi: 10.1053/j.ajkd.2018.12.044


PHARMACOLOGIC THERAPY

Medications CKD-Related Other Common Side Potential


Indication Potential Effects Contraindications
Indications
ACEi (first-line if Proteinuria HF with reduced Cough, Pregnancy; bilateral
proteinuria) reduction; delays EF; post-MI angioedema renal artery stenosis
progression of Hyperkalemia
CKD Leukopenia
Anemia
ARBs (first-line if Angioedema
proteinuria)

Ku et al. Hypertension in CKD: Core Curriculum 2019. AJKD. Doi: 10.1053/j.ajkd.2018.12.044


PHARMACOLOGIC THERAPY
Medications CKD-Related Other Common Side Potential Other
Indication Potential Effects Contraindications Considerations
Indications
Thiazide: Fluid overload; Kidney stone Hyperuricemia Hypercalcemia May be less
HCTZ May improve prevention Hypercalcemia effective at eGFR
Chlorthalidone proteinuria (if (hypercalciuria); Hyponatremia <30
Metolazone combined with NDI Hypokalemia
RAS inhibitors) Hyperglycemia

Loop: Fluid overload Heart failure; Hearing loss Gout; Bumetanide and
Furosemide Hypercalcemia Hypokalemia sulfonamide-related torsemide have
Bumetanide Hypocalcemia hypersensitivity better intestinal
Torsemide Hyponatremia absorption than
furosemide
Potassium- Fluid overload Refractory Hyperkalemia Pregnancy Avoid in patients
sparing: Hypokalemia hypomagnasemi Metabolic with significant
Triamterene a; acidosis CKD
Amiloride Lithium toxicity/ (GFR<45mL/min)
NDI

Ku et al. Hypertension in CKD: Core Curriculum 2019. AJKD. Doi: 10.1053/j.ajkd.2018.12.044


BETA BLOCKERS

Medications CKD-Related Other Potential Common Side Potential Other


Indication Indications Effects Contraindications Considerations
Selective Heart failure; Bradycardia Asthma
Metoprolol Atrial Fibrillation Hyperkalemia COPD
Nebivolol Migraines Fatigue 2nd or 3rd degree
Essential tremors Depression heart block
Anxiety disorders Sexual dysfunction
Angina
Combined a-b Heart failure Bradycardia 2nd or 3rd degree May be better
Carvedilol Atrial fibrillation Hyperkalemia heart block tolerated in lung
Labetalol Fatigue disease than
Depression selective B-
Sexual dysfunction blockers

Ku et al. Hypertension in CKD: Core Curriculum 2019. AJKD. Doi: 10.1053/j.ajkd.2018.12.044


CALCIUM CHANNEL BLOCKERS
Medications CKD-Related Other Potential Common Side Potential Other
Indication Indications Effects Contraindication Considerations
s

Dihydropiridine: Reynaud, Lower-extremity May worsen


Amlodipine Esophageal spasms edema; gingival Proteinuria
Nifedipine hypertrophy
Nondihydropyridine Proteinuria Atrial fibrillation Constipation; 2nd or 3rd degree ↑ calcineurin and
(diltiazem, verapamil) reduction gingival heart block mTOR inhibitor
hyperplasia levels

Ku et al. Hypertension in CKD: Core Curriculum 2019. AJKD. Doi: 10.1053/j.ajkd.2018.12.044


Medications CKD-Related Other Common Side Potential Other
Indication Potential Effects Contraindication Considerations
Indications s
α-Blockers; kidney Benign prostatic Orthostatic
stone passage hypertrophy Hypotension
Prazosin
Terazosin
Central α- Sedation; Depression
adrenergic bradycardia; dry
agonists (clonidine) mouth; rebound
hypertension

Vasodilators Headache; Post–myocardial


(minoxidil, tachycardia; lupuslike infarction; heart
hydralazine) syndrome failure
(hydralazine);
edema; pericardial
effusion

Ku et al. Hypertension in CKD: Core Curriculum 2019. AJKD. Doi: 10.1053/j.ajkd.2018.12.044


Medications CKD-Related Other Potential Common Side Potential Other
Indication Indications Effects Contraindication Considerations
s
Direct renin Proteinuria hyperkalemia Bilateral renal Not recommended
inhibitors reduction; if not artery for
(aliskiren) tolerating ACEi or stenosis use in combination
ARB with ACEi or ARBs
Aldosterone Proteinuria Cirrhosis + ascites Hyperklemia; May be useful in
Antagonists reduction PCOS Metabolic acidosis addition to ACE or
Primary Gynecomastia; ARB for proteinuria
Eplerenone hyperaldosteronism impotence reduction
Spirinolactone Resistant
hypertension

Ku et al. Hypertension in CKD: Core Curriculum 2019. AJKD. Doi: 10.1053/j.ajkd.2018.12.044


>18 yrs to <80 yrs with CKD

BP Below target? Target BP: < 130/80

NO
YES
Start ACEi or ARB or CCB
Continue Monitoring BP Monitor eGFR and K
Manage Lifestyle Continue BP monitoring
Manage Lifestyle

YES BP Below target? NO

Reinforce medication and lifestyle adherence


Increase ACEi/ ARB to maximum recommended dose
Consider Adding CCB or diuretic or BB

YES BP Below target? NO

Resistant Hypertension if > 3 Antihypertensives inclusive of diuretic


Initial diagnosis of Resistant Hypertension
Office BP >130/80 mm Hg in proteinuric CKD or >140/90 mm-Hg in non-proteinuric
CKD + Prescribed ≥3 antihypertensive agents at optimal doses, ideally including a
diuretic or BP at goal but requires ≥4 antihypertensive agents to do so

Exlude pseudo-resistance

Obtain 24-hour ambulatory blood pressure monitoring (ABPM)


• Rule out white-coat hypertension
• Identify the presence of a ‘non-dipper’ vs. ‘dipper’ pattern

Chronotherapy: Change ≥1 antihypertensive agents from AM to PM


Chronotherapy: Change ≥1 antihypertensive agents from AM to PM

Physiologic assessment of volume excess: Hyperactive RAAS Clues of hypertension


indications for uptitrating diuretic regimen • High PRA mediated by the SNS
• Low PRA • Aldosterone • Tachycardia
• 24-hour urine sodium >150 mmol/day breakthrough • Congestive heart
• Edema • Reduced eGFR failure
• Reduced eGFR • Refractory BP or • Anxiety symptoms
proteinuria on escalating
doses of ACE-I or ARB

Optimize diuretic regimen


• Change HCTZ to chlorthalidone • Add or substitute β-
Optimize RAAS blockade or α- + β-blockade
Maintain thiazide and add MRB
• Uptitrate ACE-I or ARB or
(spironolactone or replerenone)
‘ultrahigh’ doses
• Change thiazide to loop diuretic if eGFR
• Add MRB (spironolactone
<40 mL/min/1.73 m2
or eplerenone)
• Combined loop diuretic with distally acting
diuretic (thiazide, amiloride)
Lifestyle Modifications:
Step 1 Achieve Dry weight

Not at goal BP
>140/90

Step 2 Initial drug choices

Hypertension without Hypertension with compelling


compelling indications indications

Stage 1 Hypertension Stage 2 Hypertension


(BP 140-159/90-99 mm Hg) (BP >160/100 mm Hg)
Start an ACEI, or ARB Start a 2-Drug combination Drug(s) for
(Usually an ACEI or ARB Compelling
and a CC) Indications
Not at goal BP
>140/90

Step 3 Add a B-blocker or Clonidine

Work-up for secondary causes


Step 4 If w/u neg. add minoxidil
CONCLUSION

 It is generally accepted that a stepwise combination of lifestyle modifications and drug


therapy should be used to lower BP in CKD Patients, with escalation of efforts depending
on factors such as the severity of the BP elevation, the comorbidities present and the age
of the patient
 Lifestyle modification should be encouraged in patients with CKD to lower BP and
improve long term CV and other outcomes
 Single pill combinations may help with medication adherence
• Paul K. Whelton et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/
NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of
High Blood Pressure in Adults . Journal of the American College of Cardiology May 2018, 71
(19) e127-e248; DOI: 10.1016/j.jacc.2017.11.006
• Ku et al. Hypertension in CKD: Core Curriculum 2019. AJKD. Doi: 10.1053/j.ajkd.2018.12.044