Should I stop losartan (Angiotensin II Receptor Antagonist)-HCTZ (Hydrochlorothiazide) in a patient with worsening creatinine levels and decreased estimated Glomerular Filtration Rate (eGFR)?

Continue Losartan-HCTZ with Close Monitoring

Continue the losartan-HCTZ and recheck labs in 1-2 weeks, as a creatinine rise up to 30% and eGFR decline are expected hemodynamic effects of RAS blockade that predict better long-term renal outcomes, not harm. 1, 2

Why This Creatinine Rise is Expected and Acceptable

• Your patient's creatinine increased 26% (0.88→1.11 mg/dL), which falls within the acceptable 30% threshold for continuing ACE inhibitors or ARBs 1, 2
• The eGFR decline from 58→44 mL/min/1.73m² represents hemodynamic adjustment from efferent arteriolar vasodilation, not structural kidney damage 1, 3
• This initial GFR decrease is more pronounced in patients with proteinuric kidney disease and actually predicts slower long-term kidney function loss 1
• Guidelines explicitly state to accept creatinine rises up to 30% within 4 weeks of RAS modulator initiation—this is the expected mechanism of renoprotection 1, 2

Immediate Next Steps (Within 1-2 Weeks)

• Recheck BMP, focusing on serum creatinine, potassium, and bicarbonate 1, 2
• Assess volume status—diuretic-induced volume depletion is the most common avoidable reason for excessive creatinine rise 1
• Check blood pressure to ensure no symptomatic hypotension 2
• Review medication list for NSAIDs, which combined with losartan-HCTZ significantly worsen renal function 4

When to Actually Stop or Reduce the Medication

Only discontinue or reduce losartan-HCTZ if: 1, 2

• Creatinine rises >30% from baseline within 4 weeks
• Potassium rises >5.5-6.0 mEq/L despite dietary restriction and diuretic adjustment
• Symptomatic hypotension develops
• Evidence of bilateral renal artery stenosis emerges 3, 5

Managing the Diuretic Component

• Consider reducing the HCTZ dose if volume depletion is suspected, as thiazide-induced intravascular volume depletion amplifies the creatinine rise 1
• At eGFR 44 mL/min/1.73m², HCTZ becomes less effective—consider switching to a loop diuretic if volume control is needed 1
• The combination of losartan-HCTZ provides superior proteinuria reduction compared to losartan alone, independent of blood pressure effects 6

Critical Monitoring Parameters Going Forward

• Check creatinine and potassium 2-4 weeks after any dose adjustment, then monthly for 3 months, then every 3 months 1, 2
• Monitor for hyperkalemia more closely at this eGFR level—discontinue potassium supplements if prescribed 1
• Assess for proteinuria if not already done, as the renoprotective benefit of losartan is greatest with albuminuria present 1, 4

Why Continuation Outweighs Risks at This eGFR

• The RENAAL trial demonstrated losartan reduced doubling of serum creatinine by 25% and ESRD by 29% in patients with baseline creatinine of 1.9 mg/dL (similar to your patient's current level) 4
• Cardiovascular protection from RAS blockade remains critical at eGFR 44, as cardiovascular mortality exceeds dialysis risk in this population 1, 2
• Studies show losartan is well-tolerated even in patients with moderate-severe renal insufficiency (eGFR 10-29 mL/min/1.73m²) 7

Common Pitfalls to Avoid

• Do not stop for modest creatinine rises—this represents the therapeutic mechanism, not toxicity 1, 2
• Do not add an ACE inhibitor to losartan—dual RAS blockade increases hyperkalemia and acute kidney injury without additional benefit 4
• Screen for volume depletion before attributing creatinine rise to the medication itself 1
• Avoid NSAIDs completely—they synergistically worsen renal function with RAS blockers and diuretics 4

Additional Considerations

• If proteinuria ≥300 mg/g is present, consider adding an SGLT2 inhibitor once renal function stabilizes, as this provides additive renoprotection at eGFR ≥20 mL/min/1.73m² 2
• The favorable renal effects of losartan were demonstrated across age, gender, and racial subgroups in the RENAAL trial 4
• If hyperkalemia develops, manage with dietary potassium restriction and potassium binders rather than stopping losartan 2