Autosomal dominant tubulointerstitial kidney disease

Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a group of genetic kidney diseases that cause progressive loss of kidney function. Signs and symptoms of all forms of ADTKD include slowly worsening kidney disease (often becoming apparent by the teenage years) that ultimately results in end-stage kidney disease at some time between the ages of 20 and 70, depending on the genetic cause and severity. Urine exams of people with ADTKD show a bland urinary sediment (little blood or little or no protein). Kidney ultrasound examination is generally normal early in the disease course, but some people with ADTKD have cysts in the center of the kidneys (medullary cysts) that may be seen on an ultrasound.

There are 3 known subtypes of ADTKD, which are classified based on their genetic causes and presence of additional features:

• UMOD-related autosomal dominant tubulointerstitial kidney disease (ADTKD-UMOD) or uromodulin kidney disease (formerly known as UMOD-associated kidney disease, familial juvenile hyperuricemic nephropathy type 1, medullary cystic kidney disease type 2 (MCKD2), and uromodulin storage disease)- caused by a mutation in the UMOD gene. This is the most common subtype. The age of onset varies but kidney problems are usually noted in adolescence,and may progress to end-stage renal disease (ESRD) between the fourth and seventh decades of life. High levels of uric acid in the blood (hyperuricemia) and gout (a form of arthritis), sometimes occur as early as the teenage years.
• REN-related autosomal dominant tubulointerstitial kidney disease (ADTKD-REN) (previously known as "familial juvenile hyperuricemic nephropathy type 2") - caused by a mutation in the REN gene. Kidney disease is usually present in childhood. Many people with this subtype also have anemia in childhood (even before kidney disease begins), low or low-normal blood pressure, mildly high levels of potassium in the blood (hyperkalemia), hyperuricemia and gout.
• MUC1-related autosomal dominant tubulointerstitial kidney disease (ADTKD-MUC1) or Mucin-1 kidney disease or MKD (formerly known as medullary cystic kidney disease type 1) - caused by a mutation in the MUC1 gene. It is characterized by slowly progressive disease that leads to end-stage renal disease (ESRD) occurring at any age between 20 and 70 years. There are no other systemic features in addition to chronic kidney disease, although some develop gout in adulthood.

In some cases, the genetic cause of ADTKD in a family is not known. People with ADTKD of unknown cause typically do not have features in addition to chronic kidney disease (as is the case for MKD).

Inheritance of ADTKD is autosomal dominant, as the name implies. Most people with ADTKD have a family history of "kidney disease" (if not a family history of ADTKD specifically) or some of the other symptoms. The diagnosis of ADTKD may be suspected based on family history, symptoms, and laboratory tests, and it can be confirmed by genetic testing.

Treatment for kidney disease in people with ADTKD generally follows standard guidelines for chronic kidney disease and may involve kidney transplantation, which cures the disease. The disease does not recur in the transplanted kidney. Other treatments depend on the symptoms in each person. For example, gout may be treated with allopurinol. High meat and seafood intake could worsen gout. Treatment of anemia depends on whether it is causing symptoms. Those with ADTKD-REN are advised to avoid a low-sodium diet and non-steroidal anti-inflammatory drugs.