PharmacologyTier 1Medical Sciences concept

Uricosuric/urate-lowering effects of antihypertensive drugs (losartan)

Core concept

Urate handling is almost entirely proximal tubular - ~90% of filtered urate is reabsorbed
- URAT1 (SLC22A12) is the apical reabsorptive exchanger; GLUT9 (SLC2A9) the basolateral exit
- Blocking URAT1 -> uricosuria -> dec serum urate
Losartan is the only ARB with a clinically useful uricosuric effect - a property of the parent molecule, not of the class and not of its active metabolite E-3174
- Serum urate falls ~10-20% (roughly 0.03-0.05 mmol/L)

Drug	Effect on urate	Mechanism
Losartan	dec (uricosuric)	URAT1 inhibition
Other ARBs, ACE inhibitors	Neutral
Thiazides, loop diuretics	inc	Volume contraction -> inc proximal reabsorption; direct URAT1 stimulation
Low-dose aspirin (<300 mg)	inc	Inhibits tubular secretion
High-dose aspirin (>3 g)	dec	Inhibits reabsorption
Calcium channel blockers (amlodipine)	dec (mild)	Uricosuric
SGLT2 inhibitors	dec	Luminal glucose inhibits URAT1/GLUT9
Fenofibrate	dec	Uricosuric
Ciclosporin, tacrolimus, pyrazinamide, ethambutol	inc	dec tubular secretion
Atorvastatin	dec (mild)

Dedicated uricosurics act on the same transporter: probenecid (also blocks OAT-mediated secretion of penicillins and methotrexate), benzbromarone, lesinurad
- All require good urine output and eGFR >30; risk of urate stones - alkalinise the urine
Contrast with xanthine oxidase inhibitors (allopurinol, febuxostat) which reduce urate production
Target serum urate <0.36 mmol/L, or <0.30 mmol/L with tophi or frequent flares

Hypertension plus gout -> losartan and/or amlodipine; avoid a thiazide where an alternative exists
- Combining losartan with an SGLT2 inhibitor and a fibrate stacks three modest uricosuric effects
If a thiazide is genuinely needed for BP control, keep it and treat the urate with allopurinol - do not leave hypertension untreated
Diuretic-induced hyperuricaemia is a very common cause of a first gout attack in an older hypertensive patient
The urate-lowering effect of losartan is too small to treat gout on its own - it is a tiebreaker when choosing between equivalent antihypertensives
Asymptomatic hyperuricaemia is not itself an indication to treat

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