Can losartan (angiotensin II receptor antagonist) cause a transient increase in serum creatinine levels, indicating impaired renal function?

From the Guidelines

Yes, losartan can cause a transient increase in serum creatinine levels, but this effect is typically not a cause for concern unless the elevation is significant or persistent, as evidenced by the most recent guideline from 2022 1. This is a common effect of angiotensin II receptor blockers (ARBs) like losartan. When losartan blocks the angiotensin II receptors, it causes vasodilation of the efferent arterioles in the kidneys, which can temporarily reduce glomerular filtration rate (GFR) and lead to a modest rise in creatinine. This effect is usually most pronounced within the first few weeks of starting therapy or after dose increases. For most patients, creatinine elevations of up to 30% from baseline can be considered acceptable and often stabilize over time, as recommended by recent guidelines 1. However, if creatinine increases more than 30% or continues to rise, dosage adjustment or medication review may be necessary. Patients with pre-existing kidney disease, those on diuretics, or those taking NSAIDs concurrently may be more susceptible to this effect. Adequate hydration and monitoring of kidney function are important when starting losartan, particularly in high-risk patients. The benefits of losartan in reducing the progression of kidney disease, as shown in studies such as RENAAL 1 and IDNT, should be weighed against the potential risks of transient creatinine elevation. Recent analyses, including the kdigo 2020 clinical practice guideline for diabetes management in chronic kidney disease 1, support the use of ARBs like losartan in patients with diabetes and chronic kidney disease, despite the potential for minor increases in serum creatinine. In general, the benefits of renin-angiotensin system blockade, including losartan, in reducing kidney disease progression and cardiovascular risk, outweigh the risks of minor creatinine elevations, as long as they are properly monitored and managed. Key considerations for clinicians include:

• Monitoring serum creatinine levels regularly, especially in the first few weeks after starting losartan
• Adjusting the dosage or discontinuing the medication if creatinine levels increase by more than 30% or if there are signs of volume depletion
• Ensuring adequate hydration and monitoring kidney function in high-risk patients
• Weighing the benefits of losartan in reducing kidney disease progression against the potential risks of transient creatinine elevation.

From the FDA Drug Label

5.3 Renal Function Deterioration Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system and by diuretics.

Patients whose renal function may depend in part on the activity of the renin-angiotensin system (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion) may be at particular risk of developing acute renal failure on losartan. Monitor renal function periodically in these patients Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on losartan

The FDA drug label does indicate that losartan can cause changes in renal function, including acute renal failure, which may be associated with an increase in serum creatinine levels, indicating impaired renal function.

• Key points:
  • Losartan can cause changes in renal function
  • Patients with certain conditions (e.g. renal artery stenosis, chronic kidney disease) may be at particular risk
  • Monitor renal function periodically in these patients
  • Consider withholding or discontinuing therapy if a clinically significant decrease in renal function occurs 2

From the Research

Losartan and Renal Function

• Losartan, an angiotensin II receptor antagonist, may cause a transient increase in serum creatinine levels, indicating impaired renal function, particularly in patients with underlying renal pathology or those sensitive to reduced renal plasma flow 3.
• The ELITE trial showed a 10.5% incidence of losartan-induced renal dysfunction in elderly patients with congestive heart failure, similar to that of captopril 3.
• Case reports suggest that losartan can cause renal deterioration, which is reversible upon discontinuation of the drug, similar to ACE inhibitors 3, 4.
• However, some studies suggest that losartan may retard the progression of advanced renal insufficiency, with a significant reduction in the rate of renal function loss 5.
• The pharmacokinetics of losartan are not significantly altered in patients with renal insufficiency, and dose adjustment is not necessary 6.

Patient Populations at Risk

• Patients with bilateral renal artery stenosis, severe congestive heart failure, and severe sodium and volume depletion are at risk of losartan-induced renal dysfunction 3.
• Patients with underlying renal dysfunction, including those with chronic kidney disease, should be monitored closely when taking losartan 3, 7.
• Elderly patients with congestive heart failure may also be at risk of losartan-induced renal dysfunction 3.

Monitoring and Safety

• Renal function should be monitored in patients taking losartan, particularly in those with underlying renal pathology or at risk of renal dysfunction 3, 7.
• Losartan should be used with caution in patients with risk factors for renal dysfunction, and alternative treatments should be considered if necessary 3, 4.