Dr. Kumar’s Take:
This was a pharmacogenetics study in humans, not a head-to-head comparison of blood pressure drugs. Investigators in Shanghai gave 100 mg of losartan for 14 days to 100 hypertensive patients who also had hyperuricemia, and compared them with 100 healthy controls. They treated the URAT1 mechanism as already established rather than testing it, and asked a narrower question: does variation in the URAT1 gene change how much uric acid losartan removes? That question is worth asking, because the uric acid drop clustered almost entirely in patients carrying the TT genotype at each of the three sites examined. Losartan’s dual action is real, but the size of the uric acid benefit was not the same in every patient. This is a single centre study with 14 days of treatment, so I read it as a signal about who responds, not as a dosing rule.
Key Takeaways:
✔ 100 hypertensive patients with hyperuricemia took 100 mg of losartan for 14 days.
✔ Serum uric acid fell from 506.56±92.33 to 438.56±56.86 μM (p=0.000), and creatinine, blood urea nitrogen and fasting glucose also fell significantly.
✔ Triglycerides, total cholesterol, HDL-C, LDL-C and small dense LDL-C did not change significantly over the 14 days.
✔ Uric acid reduction was far larger in TT homozygotes than in TC or CC carriers at rs7929627, rs75786299 and rs3825017.
✔ Genotype and allele frequencies at all three sites were similar in patients and healthy controls.
Actionable Tip:
If you take losartan for high blood pressure and you also have a high uric acid level, ask your doctor to check uric acid before and after starting it, rather than assuming the drug is doing that job for you. In this study the reduction depended heavily on genotype.
Brief Summary:
This study looked at whether URAT1 gene polymorphisms change the size of losartan’s uric acid-lowering effect in hypertensive patients who also had hyperuricemia. It did not test the mechanism itself: the authors take as given that losartan lowers uric acid by inhibiting the urate transporter 1 on the brush border of proximal renal tubular cells. One hundred patients received 100 mg of losartan for 14 days, and three URAT1 variants (rs7929627, rs75786299, rs3825017) were genotyped in those patients and in 100 healthy controls.
Uric acid, creatinine, blood urea nitrogen and fasting glucose all fell significantly after 14 days. The fall in uric acid and creatinine was significantly smaller in TC and CC carriers than in TT homozygotes at all three sites, so genotype tracked with how well the drug worked.
Study Design:
- Participants: 100 patients with hypertension and hyperuricemia (46 male, 54 female, mean age 65±12 y) treated at a single hospital between 2018 and 2019, plus 100 healthy controls (48 male, 52 female, mean age 63.2±15.3 y).
- Treatment: Oral losartan 100 mg for 14 days in the patient group.
- Entry criteria: Age 45 to 70 y, systolic pressure ≥140 mmHg or diastolic pressure ≥90 mmHg, serum uric acid above 7 mg/dl (416 μM) in men or above 6 mg/dl (357 μM) in women.
- Measurements: Blood pressure plus fasting uric acid, creatinine, blood urea nitrogen, triglycerides, total cholesterol, HDL-C, LDL-C, small dense LDL-C and fasting plasma glucose, before and after treatment.
- Genetic factor: Three URAT1 loci (rs7929627, rs75786299, rs3825017) genotyped by PCR-RFLP and by mass spectrometry based genotyping, then matched against the change in each index.
Results:
- Before treatment: Patients and controls were similar in age, sex ratio, BMI, triglycerides, HDL-C, LDL-C and small dense LDL-C, and differed significantly in uric acid, creatinine, blood urea nitrogen, total cholesterol and fasting glucose.
- Genotype distribution: No significant difference in allele or genotype frequency at any of the three loci between patients and controls, and control genotypes fitted Hardy-Weinberg equilibrium.
- After 14 days of losartan: Uric acid 506.56±92.33 to 438.56±56.86 μM, creatinine 96.67±18.45 to 84.35±16.98, blood urea nitrogen 6.8±2.4 to 5.4±2.3, fasting glucose 8.9±0.6 to 7.2±0.4, all p=0.000.
- Lipids: Triglycerides, total cholesterol, HDL-C, LDL-C and small dense LDL-C showed no significant change.
- rs7929627 (TT 34, TC 34, CC 32): Uric acid fell by 123.54±46.87 in TT, 7.86±9.84 in TC and 1.85±4.07 in CC (p=0.000).
- rs75786299 (TT 28, TC 35, CC 37): Uric acid fell by 119.56±65.87, 8.96±6.76 and 1.00±5.76 respectively (p=0.000).
- rs3825017 (TT 37, TC 33, CC 30): Uric acid fell by 113.54±76.94, 6.86±9.24 and 1.24±8.43 respectively (p=0.000).
- Creatinine and urea: The creatinine reduction followed the same genotype pattern (p=0.001 for rs7929627), while the change in blood urea nitrogen did not differ significantly by genotype.
How Losartan Lowers Uric Acid:
URAT1 sits on the brush border of proximal renal tubular cells and works as a highly specific, electrically neutral urate exchanger. It reabsorbs urate and secretes a small amount of it, which is how it sets the serum urate concentration. Losartan inhibits that transporter, so less urate returns to the blood. The authors of this study take that mechanism as established and use the URAT1 genotype to explain why the same 100 mg dose produced a large uric acid drop in some patients and almost none in others.
Related Studies and Research
Vitamin C, Coffee, and Milk: Gout Risk Study. Investigates how common dietary elements influence uric acid levels and gout risk.
Uric Acid and Human Evolution. Reviews the evolutionary loss of uricase and its ties to blood pressure and metabolism.
The Glorification of Gout in Literature. Explores how gout was historically portrayed as a disease of status and intellect.
Podcast: How to Make Gout Disappear from Your Life. A comprehensive look at modern and ancient gout science, and how to beat it.
Frequently Asked Questions
Does losartan lower uric acid?
In this group it did. Across all 100 patients, serum uric acid fell from 506.56±92.33 to 438.56±56.86 μM after 14 days on 100 mg. Losartan is described here as the main drug for hypertension complicated by hyperuricemia because it addresses both problems.
Does everyone get the same uric acid benefit?
No. At each of the three URAT1 sites tested, the drop in uric acid was an order of magnitude larger in TT homozygotes than in TC or CC carriers. Variant carriers still dropped, but only slightly.
Did losartan change cholesterol or triglycerides?
Not over 14 days. Triglycerides, total cholesterol, HDL-C, LDL-C and small dense LDL-C were all unchanged, which is one of the specific things this study set out to measure.
Who was studied?
Adults aged 45 to 70 with systolic pressure of at least 140 mmHg or diastolic pressure of at least 90 mmHg, plus uric acid above 7 mg/dl in men or 6 mg/dl in women. Patients with secondary hypertension, congestive heart failure, transient ischemic attack, or hepatic and renal insufficiency from kidney disease were excluded, so these findings apply to a fairly narrow group.
Conclusion
Losartan lowered uric acid, creatinine, blood urea nitrogen and fasting glucose in hypertensive patients with hyperuricemia after two weeks of treatment, without moving lipid measures. The size of the uric acid response depended on URAT1 genotype at rs7929627, rs75786299 and rs3825017, with TT homozygotes responding strongly and TC and CC carriers barely at all. That is the practical message: if you are relying on losartan to handle a high uric acid level as well as blood pressure, measure the result rather than assume it.
