In an adult without other predisposing factors, does losartan increase the risk of nephrolithiasis?

Does Losartan Increase the Risk of Renal Stones?

Losartan does not increase the risk of nephrolithiasis in adults without other predisposing factors; in fact, it may reduce stone formation risk through its uricosuric effects and potential protective mechanisms against calcium oxalate crystallization.

Mechanism and Evidence

Losartan possesses unique uricosuric properties that distinguish it from other angiotensin II receptor blockers. The drug increases urinary uric acid excretion while simultaneously raising urine pH, which actually decreases the concentration of dihydrogen urate—the primary risk factor for uric acid crystal formation 1. This protective mechanism was demonstrated in hypertensive patients with thiazide-induced hyperuricemia, where losartan increased uric acid excretion without elevating urinary dihydrogen urate levels over 21 days of treatment 1.

Protective Effects Against Stone Formation

Research demonstrates that losartan may actively prevent calcium oxalate stone formation through multiple pathways 2:

• Losartan ameliorates calcium oxalate-induced upregulation of stone-related proteins (OPN, CD44, MCP-1) in renal tubular cells 2
• The drug inhibits NADPH oxidase and reduces oxidative stress, which are key mediators of crystal-induced renal tubular injury 2
• In animal models of hyperoxaluria, losartan treatment reduced renal crystallization 2

Important Caveats and Clinical Context

While losartan's uricosuric effect theoretically could increase uric acid stone risk, this concern has not materialized in clinical practice 1, 3. The simultaneous increase in urine pH counterbalances the increased uric acid excretion 1. However, one theoretical concern exists: the uricosuric effect of losartan may increase the frequency of calculi in the urinary tract when combined with allopurinol, as both drugs affect purine metabolism 4.

Comparison to Other ARBs

Losartan is unique among angiotensin II receptor blockers in its uricosuric properties. Irbesartan, for example, has no effect on serum uric acid levels, demonstrating that this is a losartan-specific characteristic rather than a class effect 5. This distinction is clinically relevant when selecting an ARB for patients with concurrent hyperuricemia or gout 5.

Clinical Recommendations

For adults without other stone risk factors:

• Losartan can be safely prescribed without concern for increased nephrolithiasis risk 1
• The drug may actually be preferable in hypertensive patients with hyperuricemia, as it lowers serum uric acid by 8-16% 1, 5
• Standard stone prevention measures (maintaining urine output ≥2 L/day) remain important regardless of losartan use 6, 7
• Monitor serum uric acid levels if combining losartan with allopurinol, as the hypouricemic effect may be less than additive 4

When to Exercise Caution

The theoretical risk of uric acid stone formation with losartan would be highest in patients who:

• Have pre-existing uric acid stones or cystine stones (though no evidence supports increased risk even in these populations) 4
• Are severely dehydrated or have chronically low urine output 1
• Are taking allopurinol concurrently, which may increase purine base excretion 4