Renal hypouricemia
Renal hypouricemia is a kidney disorder characterized by low levels of urate in the blood and an excessive release of urate in the urine.
Overview
Renal hypouricemia is a kidney (renal) disorder that results in a reduced amount of urate in the blood. Urate is a byproduct of certain normal chemical reactions in the body. In the bloodstream, it acts as an antioxidant, protecting cells from the damaging effects of unstable molecules called free radicals. However, because having too much urate in the body is toxic, excess urate is normally removed from the body in urine.
People with renal hypouricemia have little to no urate in their blood and release an excessive amount of it in the urine. While many affected individuals show no signs or symptoms, some develop kidney problems. After strenuous exercise, they can develop exercise-induced acute kidney injury, which causes pain in the sides and lower back, as well as nausea and vomiting that can last several hours.
Because an excessive amount of urate passes through the kidneys, individuals have an increased risk of developing kidney stones (nephrolithiasis) formed from urate crystals. These stones can damage the kidneys and lead to episodes of blood in the urine (hematuria). Rarely, people with this condition develop life-threatening kidney failure.
Frequency
The prevalence of renal hypouricemia is unknown, though at least 150 affected individuals have been described in scientific literature. The condition is thought to be most prevalent in Asian countries such as Japan and South Korea, though it has been found in Europe. It is likely underdiagnosed because it does not cause symptoms in many affected individuals.
Causes
Mutations in the SLC22A12 or SLC2A9 gene cause renal hypouricemia. These genes provide instructions for making proteins called urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9), respectively. These proteins are found in the kidneys, specifically in structures called proximal tubules, which help reabsorb needed nutrients and water into the blood while excreting unneeded substances into the urine.
Mutations lead to the production of URAT1 or GLUT9 proteins with a reduced ability to reabsorb urate into the bloodstream. Consequently, large amounts of urate are released in the urine. Researchers suspect that the resulting tissue damage may be caused by high levels of urate passing through the kidneys during exercise, the loss of the antioxidant properties of urate, or the failure to reabsorb other substances alongside urate.
Genes associated with Renal hypouricemia
- SLC22A12
- SLC2A9
Inheritance
This condition is typically inherited in an autosomal recessive pattern, meaning both copies of the SLC22A12 or SLC2A9 gene in each cell have mutations. Parents of an affected individual each carry one copy of the mutated gene but usually do not show signs or symptoms.
Sometimes, individuals with one SLC2A9 gene mutation in each cell have reduced levels of urate, though these levels are usually not as low as in those with mutations in both copies. Rarely, carriers of one mutated gene may develop urate kidney stones.