Is furosemide (Lasix) nephrotoxic?

Is Furosemide Nephrotoxic?

Furosemide can potentially cause nephrotoxicity, particularly when used at high doses or in patients with pre-existing renal dysfunction, but it is not inherently nephrotoxic when used appropriately with careful monitoring.

Mechanism of Potential Renal Effects

• Furosemide works by inhibiting sodium reabsorption in the loop of Henle, which can lead to significant diuresis and electrolyte disturbances that may affect kidney function 1, 2.
• High-dose furosemide administration has been associated with worsening renal function in heart failure patients, with one study showing that patients who received 60mg more furosemide had greater deterioration in renal function compared to those who received lower doses 3.
• Intravenous furosemide at high doses (80mg) can cause acute reduction in renal perfusion and subsequent azotemia in patients with cirrhosis and ascites 3.

Risk Factors for Furosemide-Associated Nephrotoxicity

• Pre-existing renal impairment increases the risk of furosemide-induced nephrotoxicity 1, 2.
• Hypovolemia or dehydration significantly increases the risk of kidney injury when using furosemide 2.
• Concomitant use with other nephrotoxic drugs, particularly:
  • Aminoglycoside antibiotics (increased ototoxic potential, especially with impaired renal function) 1, 2
  • Cisplatin (enhanced nephrotoxicity) 1, 2
  • NSAIDs (may reduce natriuretic effects and increase risk of renal dysfunction) 2
  • Cephalosporins (increased risk of nephrotoxicity even with minor renal impairment) 2

Clinical Evidence

• In heart failure patients, worsening renal function during furosemide therapy has been associated with increased mortality. Studies show that an increase in serum creatinine >0.3 mg/dL during hospitalization was associated with nearly 3 times greater risk of in-hospital mortality 3.
• Paradoxically, a 2015 study found that higher doses of prehospital furosemide in acute decompensated heart failure were associated with lower likelihood of creatinine increases >0.3 mg/dL during hospital course 4.
• Continuous infusion of furosemide combined with low-dose dopamine has been shown to be less nephrotoxic than intermittent bolus therapy in patients with acute decompensated heart failure 5.
• A small study showed that furosemide can reduce glomerular filtration rate and gentamicin clearance, potentially explaining the enhanced risk of nephrotoxicity when aminoglycosides and diuretics are used together 6.

Monitoring and Prevention

• Serum electrolytes, CO2, creatinine, and BUN should be determined frequently during the first few months of furosemide therapy and periodically thereafter 2.
• Careful titration of diuretic therapy is recommended to promote effective diuresis while avoiding worsening renal function 3.
• Furosemide should be used with caution and only in the case of intravascular fluid overload, as it could induce or increase hypovolemia and promote thrombosis 3.
• In patients with severe edema, furosemide should be started at appropriate doses (0.5-2 mg/kg per dose) with adequate monitoring of fluid status, electrolytes, blood pressure, and kidney function 3.
• High doses of furosemide (>6 mg/kg/day) should not be given for periods longer than 1 week 3.
• Furosemide must be stopped in the case of anuria 3.

Special Considerations

• In cirrhosis patients, intravenous furosemide can cause azotemia, and its repeated use should be minimized until its safety and efficacy are evaluated in randomized trials 3.
• In sepsis management, guidelines specifically state not to use furosemide unless hypervolemia, hyperkalemia, and/or renal acidosis are present 3.
• In pediatric patients, especially premature infants, furosemide may precipitate nephrocalcinosis/nephrolithiasis, therefore renal function must be monitored and renal ultrasonography performed 1, 2.

Conclusion

While furosemide is a valuable and widely used diuretic, it requires careful dosing and monitoring to prevent nephrotoxicity. The risk of renal impairment is particularly high in patients with pre-existing kidney dysfunction, hypovolemia, or when used in combination with other nephrotoxic medications. Appropriate patient selection, dose adjustment, and vigilant monitoring of renal function and electrolytes are essential to minimize the risk of kidney injury.