About familial gouty nephropathy
What is familial gouty nephropathy?
Autosomal dominant interstitial kidney disease describes a group of diseases affecting solely the proper function of the kidney and having the following characteristics: They are inherited in an autosomal dominant manner; kidney disease develops, and dialysis or kidney transplant is required some time between the 4th and 7th decade of life; and several types of the disease are associated with elevated uric acid concentrations in blood and gout, which usually starts in the teenage years. Not all family members are affected by gout, but many are.
There has been a lot of confusion with regards to different names given to these conditions. This has created confusion for patients and doctors alike.
The term medullary cystic kidney disease is sometimes used to describe this condition. However, many, if not most, individuals with this disease do not have medullary cysts, so this name is being used less frequently. Some doctors still use this term.
The term familial juvenile hyperuricemic nephropathy is also used. "Familial" refers to the fact that the disease is inherited. "Juvenile" refers to the fact that it is first noticed frequently in childhood. "Hyperuricemic" refers to the fact that many patients have high blood uric acid levels (this causes gout). "Nephropathy" refers to the fact that this is a kidney disease.
Autosomal dominant interstitial kidney disease currently includes the following disorders. It is likely that additional forms of this disease will be indentified.
Uromodulin associated kidney disease is the most common form of this condition. It is caused by a mutation in a gene producing a protein called uromodulin. This protein is only made in the kidney. The mutation causes affected individuals to develop gout, frequently in their teenage years, and progressive kidney disease.
Autosomal dominant interstitial kidney disease due to renin mutations is caused by mutations in the gene producing a protein called renin. Affected individuals usually develop anemia in childhood. Often, their blood potassium levels are mildly elevated, and their blood uric acid levels are also elevated. These individuals also suffer from gout frequently.
Autosomal dominant interstitial kidney disease of unknown genetic cause is the term used to describe families with this disease in whom the cause is not known. This condition is sometimes called medullary cystic kidney disease type 1. These individuals usually have chronic kidney disease but do not have gout. Researchers are now trying to find the cause of this disease.
What are the symptoms for familial gouty nephropathy?
Gout causes intense pain and swelling around one or more joints. Gout most commonly affects the joint at the base of the big toe.
The signs and symptoms of gout almost always occur suddenly, and often at night. They include:
- Intense joint pain. Gout usually affects the big toe, but it can occur in any joint. Other commonly affected joints include the ankles, knees, elbows, wrists and fingers. The pain is likely to be most severe within the first four to 12 hours after it begins.
- Lingering discomfort. After the most severe pain subsides, some joint discomfort may last from a few days to a few weeks. Later attacks are likely to last longer and affect more joints.
- Inflammation and redness. The affected joint or joints become swollen, tender, warm and red.
- Limited range of motion. As gout progresses, you may not be able to move your joints normally.
What are the causes for familial gouty nephropathy?
Gout occurs when urate crystals accumulate in your joint, causing the inflammation and intense pain of a gout attack. Urate crystals can form when you have high levels of uric acid in your blood. Your body produces uric acid when it breaks down purines — substances that are found naturally in your body.
Purines are also found in certain foods, including red meat and organ meats, such as liver. Purine-rich seafood includes anchovies, sardines, mussels, scallops, trout and tuna. Alcoholic beverages, especially beer, and drinks sweetened with fruit sugar (fructose) promote higher levels of uric acid.
Normally, uric acid dissolves in your blood and passes through your kidneys into your urine. But sometimes either your body produces too much uric acid or your kidneys excrete too little uric acid. When this happens, uric acid can build up, forming sharp, needlelike urate crystals in a joint or surrounding tissue that cause pain, inflammation and swelling.
What are the treatments for familial gouty nephropathy?
Gout medications are available in two types and focus on two different problems. The first type helps reduce the inflammation and pain associated with gout attacks. The second type works to prevent gout complications by lowering the amount of uric acid in your blood.
Which type of medication is right for you depends on the frequency and severity of your symptoms, along with any other health problems you may have.
Medications to treat gout attacks
Drugs used to treat gout flares and prevent future attacks include:
- Nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs include over-the-counter options such as ibuprofen (Advil, Motrin IB, others) and naproxen sodium (Aleve), as well as more-powerful prescription NSAIDs such as indomethacin (Indocin, Tivorbex) or celecoxib (Celebrex). NSAIDs carry risks of stomach pain, bleeding and ulcers.
- Colchicine. Your doctor may recommend colchicine (Colcrys, Gloperba, Mitigare), an anti-inflammatory drug that effectively reduces gout pain. The drug's effectiveness may be offset, however, by side effects such as nausea, vomiting and diarrhea.
- Corticosteroids. Corticosteroid medications, such as prednisone, may control gout inflammation and pain. Corticosteroids may be in pill form, or they can be injected into your joint. Side effects of corticosteroids may include mood changes, increased blood sugar levels and elevated blood pressure.
Medications to prevent gout complications
If you experience several gout attacks each year, or if your gout attacks are less frequent but particularly painful, your doctor may recommend medication to reduce your risk of gout-related complications. If you already have evidence of damage from gout on joint X-rays, or you have tophi, chronic kidney disease or kidney stones, medications to lower your body's level of uric acid may be recommended.
- Medications that block uric acid production. Drugs such as allopurinol (Aloprim, Lopurin, Zyloprim) and febuxostat (Uloric) help limit the amount of uric acid your body makes. Side effects of allopurinol include fever, rash, hepatitis and kidney problems. Febuxostat side effects include rash, nausea and reduced liver function. Febuxostat also may increase the risk of heart-related death.
- Medications that improve uric acid removal. Drugs such as probenecid (Probalan) help improve your kidneys' ability to remove uric acid from your body. Side effects include a rash, stomach pain and kidney stones.
What are the risk factors for familial gouty nephropathy?
You're more likely to develop gout if you have high levels of uric acid in your body. Factors that increase the uric acid level in your body include:
- Diet. Eating a diet rich in red meat and shellfish and drinking beverages sweetened with fruit sugar (fructose) increase levels of uric acid, which increase your risk of gout. Alcohol consumption, especially of beer, also increases the risk of gout.
- Weight. If you're overweight, your body produces more uric acid and your kidneys have a more difficult time eliminating uric acid.
- Medical conditions. Certain diseases and conditions increase your risk of gout. These include untreated high blood pressure and chronic conditions such as diabetes, obesity, metabolic syndrome, and heart and kidney diseases.
- Certain medications. Low-dose aspirin and some medications used to control hypertension — including thiazide diuretics, angiotensin-converting enzyme (ACE) inhibitors and beta blockers — also can increase uric acid levels. So can the use of anti-rejection drugs prescribed for people who have undergone an organ transplant.
- Family history of gout. If other members of your family have had gout, you're more likely to develop the disease.
- Age and sex. Gout occurs more often in men, primarily because women tend to have lower uric acid levels. After menopause, however, women's uric acid levels approach those of men. Men are also more likely to develop gout earlier — usually between the ages of 30 and 50 — whereas women generally develop signs and symptoms after menopause.
- Recent surgery or trauma. Experiencing recent surgery or trauma can sometimes trigger a gout attack. In some people, receiving a vaccination can trigger a gout flare.
Is there a cure/medications for familial gouty nephropathy?
Episodic ataxia is diagnosed using tests such as a neurological examination, electromyography (EMG), and genetic testing.
After diagnosis, EA is typically treated with anticonvulsant/antiseizure medication. Acetazolamide is one of the most common drugs in the treatment of EA1 and EA2, though it’s more effective in treating EA2.
Alternative medications used to treat EA1 include carbamazepine and valproic acid. In EA2, other drugs include flunarizine and dalfampridine (4-aminopyridine).
Your doctor or neurologist might prescribe additional drugs to treat other symptoms associated with EA. For instance, amifampridine (3,4-diaminopyridine) has proved useful in treating nystagmus.
In some cases, physical therapy may be used alongside medication to improve strength and mobility. People who have ataxia might also consider diet and lifestyle changes to avoid triggers and maintain overall health.
Additional clinical trials are required to improve treatment options for people with EA.