Which clinical signs and laboratory thresholds require temporary discontinuation of lisinopril (ACE inhibitor), spironolactone (potassium‑sparing diuretic), furosemide (loop diuretic), and hydrochlorothiazide (thiazide diuretic) to avoid renal injury, electrolyte disturbances, or hypotension?

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Hold Parameters for Lisinopril, Spironolactone, Furosemide, and Hydrochlorothiazide

Temporary Discontinuation During Acute Illness

In patients with eGFR <60 mL/min/1.73 m² (CKD stage G3a–G5) who develop serious intercurrent illness that increases acute kidney injury risk, temporarily discontinue ACE inhibitors (lisinopril), aldosterone antagonists (spironolactone), and diuretics (furosemide, hydrochlorothiazide). 1

This recommendation applies to conditions such as:

  • Severe vomiting or diarrhea causing volume depletion 1
  • Sepsis or systemic infection 1
  • Procedures requiring contrast media 1
  • Any acute illness causing dehydration or hypotension 1

Lisinopril (ACE Inhibitor) – Hold Parameters

Renal Function Thresholds

  • Hold if serum creatinine rises >30% from baseline or acute kidney injury develops 2
  • Hold during serious intercurrent illness in patients with baseline eGFR <60 mL/min/1.73 m² 1
  • Risk factors for ACE inhibitor-induced renal failure include hyponatremia, hypotension, and volume contraction 2

Electrolyte Thresholds

  • Hold if serum potassium >5.5 mEq/L 3
  • Hold if serum potassium >6.0 mEq/L (absolute contraindication to continue) 3
  • ACE inhibitors reduce renal potassium excretion, making hyperkalemia more likely when combined with potassium supplements or potassium-sparing diuretics 3, 4

Blood Pressure Thresholds

  • Hold if symptomatic hypotension develops (dizziness, syncope, altered mental status) 2
  • Asymptomatic hypotension alone is not an indication to hold unless systolic BP <90 mmHg with signs of hypoperfusion 1

Volume Status

  • Hold if clinical signs of severe volume depletion (oliguria, orthostatic hypotension, tachycardia) 2
  • Withhold diuretics for a few days before reinitiation if ACE inhibitor was held for hypotension or renal insufficiency 2

Spironolactone (Aldosterone Antagonist) – Hold Parameters

Electrolyte Thresholds

  • Hold if serum potassium >5.5 mEq/L and reduce dose by 50% 3
  • Hold if serum potassium >6.0 mEq/L (discontinue entirely) 3
  • Recheck potassium within 5–7 days after any dose adjustment until values stabilize 3

Renal Function Thresholds

  • Hold if eGFR <30 mL/min/1.73 m² (relative contraindication) 3
  • Hold during acute kidney injury or if creatinine rises significantly 1

Clinical Scenarios Requiring Hold

  • Severe diarrhea or vomiting (risk of hyperkalemia from volume depletion and reduced renal clearance) 3
  • Concurrent NSAID use (dramatically increases hyperkalemia risk) 3
  • Serious intercurrent illness in patients with baseline CKD 1

Monitoring After Hold

  • Recheck potassium and renal function within 2–3 days and again at 7 days after holding 3
  • Resume at reduced dose (e.g., 25 mg daily) once potassium <5.0 mEq/L and renal function stable 3

Furosemide (Loop Diuretic) – Hold Parameters

Electrolyte Thresholds

  • Hold if serum potassium <3.0 mEq/L 3
  • Hold if serum sodium <125 mEq/L 3
  • Loop diuretics cause significant urinary potassium and magnesium losses through increased distal sodium delivery and secondary aldosterone stimulation 1, 3

Renal Function Thresholds

  • Hold if oliguria develops (<0.5 mL/kg/hour) 3
  • Hold if acute kidney injury or creatinine rises significantly 1

Volume Status

  • Hold if signs of severe volume depletion (orthostatic hypotension, tachycardia, dry mucous membranes) 1
  • Hold if symptomatic hypotension develops 1

Clinical Scenarios Requiring Hold

  • Serious intercurrent illness (vomiting, diarrhea, sepsis) in patients with baseline CKD 1
  • Before contrast media administration in patients with eGFR <60 mL/min/1.73 m² 1

Monitoring After Hold

  • Recheck potassium and renal function within 3–7 days after holding 3
  • Resume at reduced dose once volume status normalized and electrolytes corrected 3

Hydrochlorothiazide (Thiazide Diuretic) – Hold Parameters

Electrolyte Thresholds

  • Hold if serum potassium <3.0 mEq/L 3, 5
  • Hold if serum sodium <125 mEq/L 5
  • Thiazides cause potassium depletion by blocking sodium-chloride reabsorption in the distal tubule, triggering compensatory potassium excretion 5

Renal Function Thresholds

  • Hold if eGFR <30 mL/min/1.73 m² (thiazides become ineffective) 5
  • Hold during acute kidney injury 1

Volume Status

  • Hold if signs of severe volume depletion or symptomatic hypotension 5
  • Hold during acute illness with vomiting, diarrhea, or decreased oral intake 5

Clinical Scenarios Requiring Hold

  • Serious intercurrent illness in patients with baseline CKD 1
  • Before contrast media administration in patients with eGFR <60 mL/min/1.73 m² 1
  • Unexplained neurological symptoms (nausea, vomiting, headache, confusion) suggesting hyponatremic encephalopathy 5

Monitoring After Hold

  • Recheck electrolytes and renal function within 1–2 weeks after holding 5
  • Resume at reduced dose once electrolytes normalized and volume status stable 5

Combined Therapy Considerations

Triple Therapy (ACE Inhibitor + Aldosterone Antagonist + Diuretic)

  • Monitor potassium within 2–3 days and again at 7 days after any medication change 3
  • Hold all three medications during serious intercurrent illness in patients with baseline CKD 1
  • The combination of ACE inhibitor + aldosterone antagonist dramatically increases hyperkalemia risk, especially with concurrent diuretic use 3

Escalation of Therapy Triggers Monitoring

  • Any dose increase or addition of RAAS inhibitor requires potassium recheck within 7–10 days 3
  • Any clinical deterioration (worsening heart failure, infection, dehydration) requires immediate electrolyte and renal function assessment 1

Reinitiation After Hold

  • Start with lowest effective dose 2
  • Recheck electrolytes and renal function within 2–3 days and again at 7 days 3
  • Increase dietary sodium intake temporarily to support renal perfusion 2
  • Consider reducing or temporarily discontinuing diuretic before restarting ACE inhibitor 2

Critical Pitfalls to Avoid

  • Do not continue all medications during acute illness with volume depletion in patients with baseline CKD—this is the most common cause of preventable acute kidney injury 1
  • Do not ignore asymptomatic hyperkalemia >5.5 mEq/L—reduce aldosterone antagonist dose by 50% and recheck within 1–2 weeks 3
  • Do not supplement potassium routinely in patients on ACE inhibitors + aldosterone antagonists—this combination is frequently unnecessary and potentially harmful 3
  • Do not use NSAIDs concurrently—they cause acute renal failure and severe hyperkalemia when combined with RAAS inhibitors and diuretics 3
  • Do not restart medications at full dose after holding—use cautious dose titration with close monitoring 2

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

3
Guideline

Potassium Supplementation for Hypokalemia

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

5
Guideline

Hydrochlorothiazide-Induced Electrolyte Disturbances

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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