How does furosemide (Lasix) affect estimated glomerular filtration rate (eGFR), especially in patients with chronic kidney disease, heart failure, or volume depletion?

Furosemide's Effect on eGFR

Furosemide typically causes an acute decline in eGFR through prerenal azotemia from volume depletion, reduced renal perfusion, and activation of renal afferent nerves—not through direct nephrotoxicity—and this effect is dose-dependent, reversible with volume repletion, and should not prevent its use when clinically indicated for volume overload. 1, 2

Mechanisms of eGFR Reduction

Primary Mechanism: Prerenal Azotemia

• Excessive diuresis produces volume depletion, hypotension, and reduced renal perfusion pressure, which is the dominant mechanism by which furosemide impairs kidney function. 1
• The fall in GFR during furosemide infusion is independent of volume depletion itself but is largely dependent on activation of renal afferent nerves—renal nerve deafferentation prevents the GFR decline in experimental models. 2
• Furosemide increases proximal tubule pressure, renin release, and renal nerve activity, all contributing to reduced GFR despite inhibiting tubuloglomerular feedback. 2

Acute Hemodynamic Effects

• High-dose furosemide produces acute hemodynamic worsening for 1–2 hours after administration: increased systemic vascular resistance, elevated left ventricular filling pressures, and decreased stroke volume, which collectively lower renal blood flow and GFR. 1, 3
• In septic and injured patients, furosemide has only a diuretic effect with no beneficial hemodynamic effect on the kidney—it does not increase renal blood flow or reduce renal vascular resistance. 4

Dose-Dependent Risk

• A 60 mg higher daily furosemide dose is associated with significantly worse renal function compared to lower doses, indicating clear dose-dependent nephrotoxicity risk. 1
• Worsening renal function during hospitalization (creatinine rise >0.3 mg/dL) is associated with nearly three-fold increased in-hospital mortality (OR 2.7,95% CI 1.6–4.6). 1

Clinical Context: When eGFR Decline Is Expected vs. Concerning

Expected and Acceptable eGFR Changes

• In patients with chronic kidney disease on ACE inhibitors or ARBs, a 10–20% increase in serum creatinine can be anticipated when initiating therapy and is not itself an indication to discontinue treatment—this reflects reversal of adaptive glomerular hyperfiltration and is actually a desired renoprotective effect. 5
• When volume status is maintained during furosemide administration, nephron filtration rate can remain constant despite doubled distal flow rate, indicating suppression of tubuloglomerular feedback without GFR decline. 6

Concerning eGFR Decline Triggers

• Acute renal failure during chronic furosemide use usually indicates a change in systemic hemodynamics or extracellular fluid volume: worsening heart failure with reduced cardiac output, overly aggressive diuresis, intercurrent volume depletion (diarrhea, hyperglycemia with osmotic diuresis), or sepsis. 5
• Furosemide combined with ACE inhibitors or ARBs may lead to severe hypotension and deterioration in renal function, including renal failure; dose interruption or reduction may be necessary. 7
• NSAIDs or cyclosporine co-administration precipitates acute renal failure in patients taking furosemide by causing vasoconstriction and reducing renal perfusion. 5, 7

Guideline-Based Recommendations

When NOT to Use Furosemide

• Do not use diuretics, including furosemide, to prevent acute kidney injury (Grade 1B). 1
• In patients who develop AKI, furosemide should be employed only for management of volume overload, not for renal protection (Grade 2C). 1
• Furosemide is contraindicated in anuria, severe hyponatremia (Na <120–125 mmol/L), hypovolemic states, and symptomatic hypotension. 1

Monitoring to Prevent Renal Injury

• Serum creatinine and electrolytes should be rechecked 1–2 weeks after starting furosemide and then every 1–2 weeks during dose titration. 1, 8
• An increase in serum creatinine >0.3 mg/dL should trigger reassessment of therapy because it correlates with three-fold higher mortality risk. 1
• In patients with creatinine clearance <30 mL/min, furosemide has reduced diuretic response due to impaired tubular secretion. 1

Dosing Strategy to Minimize eGFR Impact

• Employ the lowest effective dose to achieve euvolemia; for diuretic-naïve acute heart failure patients, start with 20–40 mg IV and adjust upward only if needed. 1, 8
• Avoid high-dose furosemide monotherapy in acute pulmonary edema; combine with high-dose nitrates to reduce myocardial infarction and intubation risk. 1, 3
• High doses (up to 720 mg/day orally or 1400 mg/day IV) can be safe and effective in refractory edema and renal failure when usual measures fail, but require intensive monitoring. 9

Special Populations

Heart Failure with CKD

• Always combine furosemide with an ACE inhibitor (or ARB) and a beta-blocker to prevent clinical decompensation in heart failure patients. 8
• The STRONG-HF trial excluded patients with eGFR <30 mL/min/1.73 m² and those with clear intolerance to high-dose RAAS inhibitors, which is common in advanced CKD. 5
• In patients with baseline serum creatinine ≥2.2 mg/dL, absence of hypertonic saline solution in the therapeutic regimen is a strong predictor of loop diuretic-related renal function impairment (OR 25.0,95% CI 2.07–302.53). 10

Elderly Patients

• Reduced renal mass, renal blood flow (30–35%), GFR, and tubular secretion/reabsorption in elderly patients increase exposure and risk of adverse drug reactions from renally cleared drugs like furosemide. 5
• Drug accumulation due to reduced renal excretion is the most important cause of adverse drug reactions and drug-drug interactions in older adults. 5
• Use the CKD-EPI equation (or CKD-EPI Cr-cystatin C in very elderly frail patients) to estimate eGFR, as creatinine-based equations can misclassify kidney disease by one stage in >30% of older participants due to reduced muscle mass. 5

Common Pitfalls and How to Avoid Them

• Inadequate initial dosing is a common error—loop diuretics have steep dose-response curves with a ceiling threshold; underdosing leads to treatment failure without avoiding renal risk. 3
• Aggressive diuresis without monitoring is associated with worsening renal function and long-term mortality—administer judiciously with frequent creatinine checks. 3
• Combining two diuretics markedly increases risk of potassium and magnesium depletion—check electrolytes shortly after initiating combination therapy and periodically thereafter. 3
• Furosemide transiently worsens hemodynamics in the first 1–2 hours—consider adding nitrate therapy for moderate-to-severe pulmonary edema to mitigate this effect. 3
• In truly anuric ESRD patients, furosemide is ineffective—urgent dialysis or ultrafiltration is required instead. 1