Traditionally the term ‘familial juvenile hyperuricaemic nephropathy (FJHN)’ has been applied to this condition. Initially it was thought that the kidney disease was due to damage caused by urate accumulation and/or gout. We now know that is not quite accurate and we think a better term is Familial Uromodulin Associated Nephropathy or FUAN. A recent consensus conference has coined the term ‘Autosomal dominant tubulointerstitial kidney disease’ (ADTKD) which includes FUAN as well as some other gene mutations with close similarities.
Familial Uromodulin Associated Nephropathy (FUAN) is a spectrum of disorders that runs in families. Males and females are affected equally. Typically it is a silent disease and patients have kidney impairment for many years before the illness becomes apparent. Sometimes the first evidence for this condition is found in teenagers.
Some patients will notice that they are increasingly thirsty and have to get up at night to pass urine. Some will experience fatigue.
About half of all patients with FUAN develop gout. This is an important symptom that provides a useful clue to the diagnosis, particularly if the gout presents in young people. This form of gout is different from the common condition affecting older people, usually men, that is associated with high blood pressure, obesity and diabetes.
FUAN patients usually develop kidney failure between the ages of 30 and 60, leading to the eventual need for dialysis or transplantation.
It can be difficult to make the right diagnosis and some patients with FUAN are diagnosed late or not at all. This is because each of the individual findings from the tests outlined below are not enough by themselves to confirm the diagnosis. Getting a detailed family health history is important
The level of kidney function is made by a simple blood test based on serum urea and creatinine measurements (see Stages of Chronic Kidney Disease (CKD))
Gout is caused by excess uric acid. High levels of uric acid in the blood are found in two thirds of FUAN patients. However not all of those with high uric acid develop the symptoms of gout.
In a minority of patients an ultrasound examination of the kidneys may show the presence of tiny cysts. As the illness progresses, the kidneys typically shrink in size and this can also be seen on an ultrasound scan. If a kidney biopsy is done, it typically shows “interstitial nephritis and fibrosis”. Visit the Clinicians page for more information on kidney biopsies.
Currently there is no cure for FUAN. Patients presenting with gout should be treated conventionally with a drug called Allopurinol, which blocks the production of uric acid. If Allopurinol is not well tolerated an effective alternative is Febuxostat. These drugs are very effective in preventing further attacks of gout. However there is no evidence that reduction of uric acid slows the progression of FUAN.
If kidney failure reaches an advanced stage patients will require renal replacement therapy (RRT) – either dialysis or transplantation. Transplantation is very successful in FUAN patients, partly because of their younger age. FUAN does not reoccur in the transplanted kidney. If a living kidney transplant is being considered from an immediate relative, it is important to know that they are not at risk of developing FUAN themselves.
In my late teens and early 20’s I had a few gout attacks. These were treated with allopurinol at the time.
In 1988 when I was 29 years old I applied for additional life insurance cover and was sent for a medical examination. The examining doctor referred me to my own GP as my blood pressure reading was 180/120! I had never felt unwell so was rather shocked, especially when my GP had me admitted to hospital in a matter of days.
In hospital I underwent a series of tests and was initially prescribed Allopurinol and Adalat to bring my blood pressure down to normal. After two weeks of investigations and tests, the consultant concluded that my condition was due to familial gouty nephropathy. My father had died from kidney failure aged 46, one of his sisters also had the condition and also his maternal grandmother.
Over the next 20 years as the kidney function gradually deteriorated, the number and range of drugs steadily increased. Whilst I was deteriorating on blood tests, due to the slow progression I just adjusted without noticing any symptoms apart from tiredness and a lack of drive at times.
During that time my son and daughter were born. They were regularly checked for this condition and my daughter was diagnosed with it when she was about 11 or 12.
In 2009 things came to a head. My kidneys stopped functioning in the January and I started automated peritoneal dialysis at home overnight. This allowed me to continue working without interruption but had a drawback in that I had to be in bed by 9.00pm each night to allow sufficient time for the dialysis to complete.
In May 2009 I was fortunate enough to receive a kidney transplant. It was a perfect match and ‘woke up’ very quickly. All of a sudden my life changed back to normal. The existing drugs and diets were stopped as I only need anti-rejection drugs now. There are a few minor restrictions on what I can eat and alcohol consumption has to be sensible.
Now four years later the kidney continues to function well. The freedom of being able to live a normal life once again is priceless and I look forward to many more years of enjoying life. Rarely does a day go by without me acknowledging how lucky I am. This is all due to the donor for whom I shall forever be grateful.
The Purine Metabolic Patients Association (PUMPA) provides information and support for patients and their families. On Saturday 23rd March 2013 a FUAN Patient Support meeting was held at St Thomas’ Hospital London. A report of the event can be found here.
An ADTKD/UMOD Patient Information Day was held in London on Saturday 15th September 2018. A summary and photos of the event can be found below. ADTKD/UMOD patient information day summary
FUAN is a genetic disease cause by several different genetic abnormalities. The most frequent and well recognised is a mutation of the Uromodulin (Umod) gene. It is not clear how this leads to progressive kidney damage and it is currently the subject of intensive research. The Umod gene is responsible for making the protein uromodulin, also known as Tamm-Horsfall protein, which is important in the function of the tubules of the kidney. Further information about the genetics of FUAN can be found here.
Uromodulin is normally excreted into the tubule and ends up in the urine. In FUAN it seems to travel in the opposite direction and ends up between the tubules of the kidneys (the interstitium). Why this causes inflammation (interstitial nephritis) and fibrosis is not clear.
In families where Umod mutations are the cause of FUAN, the condition is inherited from one generation to the next in a pattern known as autosomal dominant inheritance. Everybody has two copies of the Umod gene, one from each parent. One copy of the faulty gene is enough to cause illness. There is a fifty-fifty chance that a child born to an affected person will receive the abnormal gene and later develop FUAN.
Additional gene mutations thought to be able to cause FUAN are still being researched.
The ADTKD Rare Disease Group (RDG) is working with international partners with the aim of finding new and improved treatments, and to empower patients. A first step is to compare the symptoms and genetic markers of ADTKD. To do this the RDG is registering patients with this condition in the National Renal Rare Disease Registry (RaDaR). The database will be used to find suitable participants for future research trials into the effectiveness of new treatments. If you are interested in finding out more about the registry RaDaR or the activity of the RDG please visit the ADTKD RDG page.