What is the treatment of resistant hypertension in patients with Chronic Kidney Disease (CKD) and End-Stage Renal Disease (ESRD)?

Treatment of Resistant Hypertension in CKD and ESRD

The management of resistant hypertension in CKD and ESRD requires a combination of optimized diuretic therapy, complementary antihypertensive medications with different mechanisms of action, and aggressive sodium restriction. 1

Definition and Prevalence

Resistant hypertension in CKD is defined as:

• BP ≥130/80 mmHg despite using ≥3 antihypertensive medications with complementary mechanisms of action (including a diuretic) OR
• BP controlled but requiring ≥4 antihypertensive medications 1

Resistant hypertension is extremely common in CKD patients, affecting approximately 40% of individuals in the CRIC Study, with higher prevalence among:

• Older individuals
• Men
• African Americans
• Patients with diabetes
• Those with higher BMI 1

Diagnostic Approach

Before intensifying therapy, rule out pseudo-resistance:

• Confirm medication adherence (accounts for ~50% of apparent resistant hypertension)
• Verify proper BP measurement technique
• Exclude white-coat hypertension using ambulatory or home BP monitoring
• Identify interfering substances (NSAIDs, oral contraceptives)
• Evaluate for secondary causes of hypertension 1, 2

Treatment Algorithm

Step 1: Optimize Non-Pharmacological Interventions

• Implement strict sodium restriction (critical in CKD due to impaired sodium excretion) 1, 3
• Recommend DASH diet with modifications appropriate for CKD stage 1
• Promote weight loss in overweight/obese patients 1
• Encourage regular physical activity (structured exercise program) 1
• Limit alcohol consumption (≤2 drinks/day for men, ≤1 drink/day for women) 1

Step 2: Optimize Diuretic Therapy

• Diuretic optimization is the cornerstone of resistant hypertension management in CKD 3, 2
• For CKD stages 1-3: Use thiazide or thiazide-like diuretics (chlorthalidone preferred over hydrochlorothiazide) 3
• For CKD stages 4-5 (non-dialysis): Consider chlorthalidone (evidence from CLICK trial shows effectiveness) 3
• For ESRD on dialysis: Focus on volume control through ultrafiltration 4

Step 3: Optimize RAAS Blockade

• Use ACE inhibitor or ARB at maximum tolerated dose, especially in patients with albuminuria 1
• Monitor for hyperkalemia and acute kidney injury 1

Step 4: Add Complementary Antihypertensive Medications

• Add long-acting dihydropyridine calcium channel blocker 3
• Consider beta-blocker if additional BP lowering needed 1

Step 5: Add Mineralocorticoid Receptor Antagonist

• Add low-dose spironolactone (12.5-25 mg daily) to existing regimen 1
• Monitor potassium levels closely, especially in advanced CKD 3
• Consider alternative MRAs like eplerenone if spironolactone not tolerated 1

Step 6: Consider Additional Therapies

• Alpha-blockers (e.g., doxazosin)
• Central-acting agents (e.g., clonidine)
• Direct vasodilators (e.g., hydralazine, minoxidil) 1

Special Considerations

For ESRD on Dialysis

• Focus on volume control through appropriate dry weight assessment and ultrafiltration 4
• Consider longer or more frequent dialysis sessions if BP remains elevated 4
• Medication timing is critical - administer non-dialyzable antihypertensives after dialysis 4

For Diabetic CKD

• Target BP <130/80 mmHg 1
• Consider SGLT2 inhibitors for their BP-lowering and kidney-protective effects 4

Monitoring and Follow-up

• Check for postural hypotension regularly 1
• Monitor electrolytes, especially potassium, when using RAAS blockers and MRAs 3
• Assess medication adherence at each visit 1

Pitfalls and Caveats

1. Avoid NSAIDs as they can worsen BP control and kidney function 1
2. Be cautious with dual RAAS blockade (ACE inhibitor + ARB) due to increased risk of hyperkalemia and acute kidney injury
3. Recognize that true resistant hypertension is less common than apparent resistant hypertension due to poor adherence 1
4. Non-medical interventions like renal denervation have not shown sustained success and should not be routinely recommended 1
5. Potassium supplementation should be avoided in CKD patients on RAAS blockers or MRAs due to hyperkalemia risk 1

By following this structured approach to resistant hypertension in CKD and ESRD, clinicians can improve BP control and potentially reduce cardiovascular and renal outcomes in this high-risk population.