Autosomal dominant tubulointerstitial kidney disease due to UMOD mutations

Other Names: ADTKD-UMOD; Autosomal dominant medullary cystic kidney disease type 2 (former); UMOD-related ADTKD; Autosomal dominant medullary cystic kidney disease type 2; MCKD2; UMOD-related autosomal dominant tubulointerstitial kidney disease; Familial juvenile hyperuricemic nephropathy type 1; Medullary cystic kidney disease 2 (former); Familial Juvenile Hyperuricemic Nephropathy 1; UMOD-Associated Kidney Disease; Autosomal Dominant Tubulointerstitial Kidney Disease, UMOD-Related; Uromodulin kidney disease; Uromodulin-associated kidney disease; ADTKD due to UMOD mutations

Autosomal dominant tubulointerstitial kidney disease due to UMOD mutations (ADTKD–UMOD) is an inherited disorder that causes a gradual loss of kidney function that eventually leads to the need for kidney transplantation or dialysis between the ages of 30 and 70. Patients with ADTKD-UMOD have high blood levels of uric acid before kidney failure develops, and some affected individuals may develop gout. Gout is a form of arthritis (inflammation) that occurs often in the big toe, ankle, knee, or other joints.

Epidemiology

The exact prevalence of autosomal dominant tubulointerstitial kidney disease due to UMOD mutations (ADTKD-UMOD) is unknown. One study found the prevalence in Austria to be about 1-2 cases per million people. Less than 1% of people with kidney disease have ADTKD-UMOD.

Cause

ADTKD-UMOD is caused by a mistake (mutation) in the UMOD gene, which leads to the build-up of the altered uromodulin protein in the tubules of the kidney, leading to slow loss of kidney function.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

Autosomal dominant tubulointerstitial kidney disease due to UMOD mutations (ADTKD-UMOD) is inherited in an autosomal dominant pattern. All individuals inherit two copies of each gene. In autosomal dominant conditions, having a mutation in just one copy of the associated (UMOD) gene causes the person to have the disease. Some people are born with an autosomal dominant condition due to a new genetic mutation (de novo) and do not have a history of this condition in their family. There is nothing either parent can do, before or during pregnancy, to cause a child to have this. Each child of an individual with ADTKD-UMOD has a 50% or 1 in 2 chance of inheriting the UMOD mutation and ADTKD-UMOD. Children who inherit the UMOD mutation will have ADTKD-UMOD, although they could be more or less severely affected than their parent.

Signs and symptoms

The most common symptom of autosomal dominant tubulointerstitial kidney disease due to UMOD mutations (ADTKD-UMOD) is gout occurring in the teenage or young adult years. Gout may not occur in all patients. Bed wetting (enuresis) is a little more common in individuals with ADTKD-UMOD than the general population. Kidney disease is identified by an increase in the blood creatinine level. This is usually detected in the teenage years, but may start at any age.

Diagnosis

ADTKD-UMOD is defined by the presence of a heterozygous pathogenic variant in UMOD, the gene encoding uromodulin. The majority of persons with ADTKD-UMOD have the following laboratory test abnormalities: elevated serum creatinine (decreased estimated glomerular filtration rate), bland urinary sediment, elevated serum urate level, and reduced fractional excretion of uric acid. In children with the disorder, serum creatinine levels may be normal but elevated serum urate levels are usually present.

Treatment

Treatment for autosomal dominant tubulointerstitial kidney disease due to UMOD mutations (ADTKD-UMOD) is based on managing the symptoms. Gout can be prevented with medications such as allopurinol and febuxostat. At present, there are no specific treatments for worsening kidney function. Eventually, patients may need a kidney transplant or dialysis. Live donor kidney transplantation is the optimal treatment for worsening kidney disease, and patients who undergo kidney transplant for this condition do extremely well. The condition does not come back in the transplanted kidney.

Prognosis

The long-term outlook for people with autosomal dominant tubulointerstitial kidney disease due to UMOD mutations is good, though patients will often need a kidney transplant or start dialysis between the ages of 30 and 70. At this point, it is difficult to predict at what age patients will develop end-stage kidney failure.

NIH genetic and rare disease info

• NIH info on Autosomal dominant tubulointerstitial kidney disease due to UMOD mutations

Autosomal dominant tubulointerstitial kidney disease due to UMOD mutations is a rare disease.