What to do with a patient with Chronic Kidney Disease (CKD) on lisinopril (Angiotensin-Converting Enzyme Inhibitor) who develops hyperkalemia and hypertension?

Management of CKD Patient on Lisinopril with Hyperkalemia and Hypertension

Do not discontinue lisinopril immediately—hyperkalemia associated with RAS inhibitors can and should be managed with potassium-lowering measures rather than stopping the ACE inhibitor, which provides critical kidney and cardiovascular protection. 1

Initial Assessment and Monitoring

Verify true hyperkalemia and assess severity:

• Confirm potassium level is not pseudo-hyperkalemia from hemolysis or improper sampling 1
• Check potassium within 2-4 weeks of any ACE inhibitor dose change 1
• Classify severity: mild (5.0-5.5 mEq/L), moderate (5.5-6.0 mEq/L), or severe (>6.0 mEq/L) 1
• Obtain ECG if potassium >6.0 mEq/L to assess for cardiac effects 1

Review current medications and identify contributing factors:

• Assess for dual RAAS blockade (ACE inhibitor + ARB + direct renin inhibitor combinations are contraindicated) 1, 2
• Identify potassium-sparing diuretics (spironolactone, amiloride, triamterene), NSAIDs, potassium supplements, or salt substitutes 1, 2
• Check baseline eGFR and recent creatinine trends 1

Step-by-Step Management Algorithm

Step 1: Implement Potassium-Lowering Measures FIRST

Dietary modification:

• Restrict dietary potassium intake (avoid high-potassium foods: bananas, melons, orange juice, salt substitutes) 1, 3
• Provide specific dietary counseling on low-potassium diet 3

Medication adjustments (other than lisinopril):

• Discontinue potassium supplements and potassium-containing salt substitutes 1, 2
• Stop or reduce potassium-sparing diuretics if present 1, 2
• Discontinue NSAIDs if being used 1, 2
• Separate lisinopril dosing from other medications by 3+ hours if starting potassium binders 1

Add loop or thiazide-type diuretics for dual benefit:

• Thiazide-type diuretics (particularly chlorthalidone) are effective for hypertension control AND reduce potassium levels in CKD stage 4 4
• Loop diuretics enhance potassium excretion while addressing volume-dependent hypertension 1
• Lisinopril attenuates potassium loss from thiazide diuretics, making this combination rational 2

Step 2: Consider Potassium Binders for Persistent Hyperkalemia

If potassium remains elevated despite above measures:

Patiromer (preferred newer agent):

• Starting dose: 8.4 g once daily, can titrate up to 25.2 g daily 1
• Onset of action: approximately 7 hours 1
• Proven effective in CKD patients on RAAS inhibitors with or without diuretics 1, 5
• Well tolerated; most common side effect is mild-to-moderate constipation (7.6-14.4%) 1, 5
• Monitor for hypomagnesemia and hypocalcemia (rare) 1
• Must separate from other oral medications by 3+ hours 1

Sodium zirconium cyclosilicate (SZC) (alternative):

• Starting dose: 10 g three times daily for 48 hours, then 5-15 g once daily for maintenance 1
• Faster onset than patiromer (4 hours) 1
• Effectively maintains normokalemia (93% of patients achieving K+ ≤5.1 mEq/L) 1
• Monitor for potential hypercalcemia (rare but reported) 1

Avoid sodium polystyrene sulfonate (SPS):

• Associated with serious gastrointestinal adverse events including intestinal ischemia and colonic necrosis 1
• Inconsistent efficacy and variable onset of action 1

Step 3: Optimize Lisinopril Dosing

Continue lisinopril at current dose if:

• Potassium is controlled with above measures 1
• Creatinine has not risen >30% within 4 weeks of initiation or dose increase 1
• No symptomatic hypotension present 1
• eGFR remains >15 ml/min per 1.73 m² 1

The KDIGO 2024 guidelines explicitly state to continue ACE inhibitors even when eGFR falls below 30 ml/min per 1.73 m² 1, 6

Consider dose reduction or discontinuation ONLY if:

• Hyperkalemia remains uncontrolled despite dietary restriction, medication adjustments, diuretics, AND potassium binders 1
• Symptomatic hypotension develops 1
• Creatinine rises >30% within 4 weeks 1
• eGFR <15 ml/min per 1.73 m² with uremic symptoms that might improve with discontinuation 1

Step 4: Address Hypertension with Additional Agents

If blood pressure remains uncontrolled on lisinopril:

Add long-acting dihydropyridine calcium channel blocker:

• Amlodipine or similar agents provide additive blood pressure reduction 4
• No increased hyperkalemia risk 4

Consider SGLT2 inhibitor if diabetic or albuminuric:

• Recommended for CKD patients with eGFR ≥20 ml/min per 1.73 m² and diabetes 1
• Also recommended for non-diabetics with urine ACR ≥200 mg/g 1
• Provides cardiovascular and kidney protection beyond blood pressure lowering 1
• May modestly reduce potassium levels 1

For resistant hypertension, add spironolactone cautiously:

• Effective for resistant hypertension in CKD 1, 4
• Requires careful potassium monitoring (check within 2-4 weeks) 1
• Consider combining with chlorthalidone to mitigate hyperkalemia risk 4
• Newer non-steroidal mineralocorticoid receptor antagonists (finerenone) may be considered for diabetic patients with eGFR >25 ml/min per 1.73 m² and controlled potassium 1

Target blood pressure:

• Systolic BP 130-139 mmHg for most CKD patients 1
• Systolic BP 120-129 mmHg for CKD with eGFR >30 ml/min per 1.73 m² if tolerated 1
• Individualize based on age (130-139 mmHg for age ≥65 years) and tolerability 1

Critical Monitoring Schedule

Potassium and creatinine monitoring:

• Check within 2-4 weeks after any intervention (medication change, binder initiation, dose adjustment) 1
• Once stable, monitor every 3 months or more frequently based on CKD stage 1

Blood pressure monitoring:

• Home blood pressure monitoring preferred over office readings 1
• Target consistent readings in therapeutic range 1

Common Pitfalls to Avoid

Do not combine multiple RAAS inhibitors:

• ACE inhibitor + ARB combinations increase hyperkalemia and acute kidney injury without cardiovascular or renal benefit 1, 2
• This combination is explicitly contraindicated 1

Do not prematurely discontinue lisinopril:

• Hyperkalemia is manageable with medical interventions in most cases 1
• Discontinuing RAAS inhibition removes critical kidney and cardiovascular protection 1

Do not use polyacrylonitrile dialysis membranes if patient progresses to dialysis:

• Risk of anaphylactoid reactions with ACE inhibitors 6, 2

Do not ignore volume status:

• Volume overload is a major driver of hypertension in CKD 1
• Diuretics are cornerstone therapy for both hypertension and hyperkalemia management 1

When to Refer to Nephrology

Consider nephrology referral for:

• eGFR <30 ml/min per 1.73 m² for discussion of renal replacement therapy 1
• Persistent hyperkalemia despite maximal medical management 1
• Resistant hypertension requiring complex medication regimens 1
• Uncertainty about etiology of kidney disease 1
• Significant increases in albuminuria despite good blood pressure control 1