Introduction:
Hypouricemia, characterized by abnormally low uric acid levels in the blood, remains a fascinating condition in nephrology and metabolic medicine. While most discussions surrounding uric acid tend to focus on hyperuricemia and its link to conditions like gout (accumulation of urate crystals in the joint, leading to inflammation and pain) and kidney stones, hypouricemia has received far less attention.
Individuals with renal hypouricemia show little or no uric acid in their blood; they release an excessive amount of it in the urine. In various patients, renal hypouricemia leads to no signs or symptoms. However, certain individuals with this problem develop kidney issues. After strenuous exercise, they can develop exercise-induced acute kidney injury, which causes pain in their sides and lower back, as well as nausea and vomiting that can last several hours.
What Is Hypouricemia?
Hypouricemia has abnormally low uric acid levels in the bloodstream, typically below 2 milligrams per deciliter (119 micromoles per liter). While the primary cause of hypouricemia is genetic, it can also result from various acquired conditions. Hypouricemia can be of two types – primary (inherited) and secondary (acquired) forms.
Primary Hypouricemia:
Primary hypouricemia is typically a genetic condition caused by gene mutations responsible for uric acid transport and metabolism. There are several types of primary hypouricemia, the most well-known being Type 1 and Type 2.
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Type 1 Primary Hypouricemia: Type 1 hypouricemia is caused by mutations in the SLC22A12 gene, which encodes a urate transporter called URAT1. URAT1 is responsible for reabsorbing uric acid in the kidneys. Mutations in this gene alter the function of URAT1, leading to excessive excretion of uric acid in the urine.
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Type 2 Primary Hypouricemia: Type 2 hypouricemia is associated with mutations in the SLC2A9 gene, encoding a transporter known as GLUT9. GLUT9 is involved in both uric acid reabsorption and secretion in the kidneys. Mutations in this gene can either reduce or increase uric acid levels in the blood, depending on the specific mutation.
Secondary Hypouricemia:
Secondary hypouricemia is typically acquired, resulting from various medical conditions, medications, or dietary factors.
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Medications: Certain medications, including Allopurinol and Probenecid, can lower uric acid levels in the blood. Allopurinol is commonly prescribed to lower uric acid levels in patients with gout, while Probenecid increases uric acid excretion and is sometimes used to treat hyperuricemia.
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Diet: A diet low in purines, found in foods like red meat, seafood, and beer, can lead to reduced uric acid production in the body. This is typically a non-problematic cause of hypouricemia.
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Kidney Disease: Kidney diseases, such as chronic kidney disease (longstanding kidney disease leading to renal failure), can lead to hypouricemia by impairing the kidney's ability to filter uric acid from the blood.
How Does Uric Acid Affect the Body?
Uric acid is a body waste product. It is formed when the purines break down. Purines are a natural substance present in the body. They are also found in foods like shellfish and alcohol. They can also be synthesized in the body as the DNA (deoxyribonucleic acid) is broken down. When purines in the blood are broken down to uric acid, it is removed from the blood when they urinate or have a bowel movement.
However, if the body makes excessive uric acid or the kidneys are not working properly, uric acid can accumulate in the blood. Uric acid levels can also elevate when an individual takes medicines like Aspirin, diuretics, and Niacin. Then crystals of uric acid might form in the joints, which causes painful inflammation. This condition is known as gout. It might also lead to kidney stones.
What Are the Effects of Hypouricemia on Kidneys?
Hypouricemia can have various effects on the kidneys, depending on its underlying cause. Understanding these effects is essential for proper diagnosis and management of the condition.
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Hypouricemic Nephropathy: In some cases, hypouricemia can lead to a unique condition known as hypouricemic nephropathy. This is characterized by crystalline deposits of uric acid in the renal tubules, which can cause kidney damage and dysfunction. It is more commonly observed in individuals with primary hypouricemia.
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Nephrolithiasis (Kidney Stones): Hypouricemia, particularly when associated with primary hypouricemia type 1, can increase the risk of kidney stone formation. Reduced uric acid levels in the urine decrease its solubility, leading to the formation of uric acid stones. These stones can obstruct the urinary tract and cause significant pain and discomfort.
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Reduced Uric Acid Handling: When hypouricemia is caused by kidney disease, the primary concern is impaired kidney function. Kidneys play a crucial role in regulating uric acid levels. When they are compromised, uric acid can accumulate in the body, leading to complications like gout and other uric acid-related conditions.
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Complications in Transplants: Hypouricemia can be a concern for individuals undergoing kidney transplantation. The mismatch between a donor kidney that efficiently excretes uric acid and a recipient with hypouricemia can lead to an imbalance and the risk of kidney damage.
Hypouricemia is regarded as a biochemical disorder with no clinical importance other than as a marker of underlying disease. However, people with progressive weakening of renal tubules may have an increased incidence of acute kidney injury. Although usually benign, idiopathic renal hypouricemia (low levels of blood uric acid levels with an unknown cause) might lead to a higher risk of exercise-induced acute kidney failure. It has also been proved that hypouricemia can worsen conditions such as rheumatoid arthritis (an inflammatory condition affecting the joints of the hands and feet), particularly in combination with low Vitamin C uptake, due to free radical damage.
How Is Hypouricemia Managed?
The management of hypouricemia depends on its underlying cause. For individuals with primary hypouricemia, treatment might involve managing the symptoms, like addressing kidney stones or nephropathy. In some cases, dietary and lifestyle modifications may be recommended, including a purine-rich diet to help raise uric acid levels to some extent. In cases of secondary hypouricemia resulting from medications or dietary factors, treatment may involve discontinuing the causative agent, modifying the medication regimen, or adjusting the diet.
For individuals with hypouricemia associated with kidney disease, the primary focus is on managing the underlying kidney condition. This may include treating the kidney disease and ensuring proper hydration to help with uric acid excretion.
Conclusion
Hypouricemia can lead to kidney stone formation, hypouricemic nephropathy, and complications in kidney transplants. Therefore, a planned approach to treatment, addressing the specific cause and managing the associated kidney-related issues, is essential for individuals with hypouricemia. Nephrologists and other healthcare professionals are critical in diagnosing and managing this unique condition to ensure optimal kidney health and overall patient well-being.
Hypouricemia, while less discussed than its counterpart, hyperuricemia, is a condition with significant implications for kidney health. Whether it is primary hypouricemia caused by genetic mutations or secondary hypouricemia resulting from medications, diet, or kidney disease, understanding the underlying causes and potential complications is vital for both diagnosis and management.
