About dRTA

Primary distal renal tubular acidosis (primary dRTA) is a rare genetic condition that results in problems with kidney function, bone formation, hearing, and the management of potassium, calcium, and pH levels in the body. The symptoms of primary dRTA most often appear in babies; however, there are rarer forms that start in older children and adults.

The first signs of primary distal renal tubular acidosis (primary dRTA) are typically problems eating, problems gaining weight (failure to thrive), frequent urination, extreme thirst, weakness, dehydration, constipation or diarrhea, and extreme tiredness. These signs are directly related to having blood with low pH levels (a medical condition called metabolic acidosis). Other early signs may be bowing of lower leg bones or hearing loss. Hearing loss in primary dRTA can occur in infancy or later in life and usually affects both ears and gradually worsens. Infants and children may also be diagnosed with rickets and have weak soft bones that result in bowing of the lower legs.

Primary distal renal tubular acidosis (primary dRTA) can be inherited or caused by a new genetic change in an individual. When inherited, it can be either autosomal recessive or autosomal dominant.  We have two copies of the genes that cause primary dRTA, one from our mother and one from our father. In autosomal recessive cases, both parents are typically carriers of the condition, meaning they have a genetic change in one of their two copies of the gene that cause it to not work as expected. It is currently thought that most carriers for primary dTRA do not show features of the condition themselves; however, individuals with changes in one copy of the gene ATP6V1B1 can have incomplete dRTA (these individuals have mild acidification in their kidneys which does not typically affect blood pH; they can also have high calcium in their urine and kidney stones). When both parents are carriers for changes in the same gene, each of their children has a 25% chance, or 1 in 4 chance, of inheriting both genetic changes and having the condition. In autosomal dominant cases, a genetic change in one copy of a gene is enough to cause disease. Most individuals with autosomal dominant primary dTRA are thought to have a new genetic change that was not inherited from a parent (also called de novo). However, sometimes this change is inherited from a parent. Each child of an individual with autosomal dominant primary dRTA has a 50% of inheriting the genetic change.  Individuals with primary dTRA can have variable presentations, even in the same family.  A negative family history cannot rule out the possibility of disease.

Diagnosing primary distal renal tubular acidosis (primary dRTA) often requires an examination by a doctor combined with a series of blood and urine tests. First, if a patient has symptoms of primary dRTA disease on exam, blood and urine tests will be done. Initial blood tests will look at the levels of electrolytes (such as potassium, sodium, and chloride), carbon dioxide (an acid), bicarbonate (a base), and pH. Initial urine tests will measure urinary electrolytes and pH levels. If testing finds a high urine pH, a normal blood anion gap, low serum potassium, and low blood pH levels it is suggestive of primary dRTA as a possible diagnosis. Diagnosis may also involve imaging of the kidneys, bones, and inner ear. A blood test that looks for specific genetic variants may also aid in the diagnosis.

Testing for primary distal renal tubular acidosis (primary dRTA) often takes a series of tests. If an individual has symptoms of primary dRTA disease, testing usually starts with a blood test looking at the potassium levels and pH. Testing may also involve imaging of the kidneys, bones, and inner ear.  If the potassium levels and pH are low, there are signs of primary dRTA, and other non-genetic causes are ruled out, the doctor might order a genetic test which looks at the genes we currently think are related to dRTA.

The treatment for primary distal renal tubular acidosis (primary dRTA) focuses on managing the pH levels of the blood using medicines to make the blood less acidic and keep the pH in the normal range This is called alkali therapy and usually involves giving sodium bicarbonate or sodium citrate several times a day. With treatment, there is no decrease in life expectancy for a patient diagnosed with primary dRTA; however, there can still be health issues such as hearing loss or kidney problems that require close monitoring by an experienced doctor. As of 2021, there is not a cure for primary distal renal tubular acidosis (primary dRTA); however, an extended-release form of alkali therapy (Advicenne’s ADV7103) is approved in Europe for the treatment of dRTA and is in clinical trials in the USA and Canada to examine its safety and effectiveness in maximizing alkali therapy over a 12-hour period and decreasing treatment to twice a day.

As of April 2021, there is one clinical trial listed on Clinicaltrials.gov sponsored by Advicenne for primary distal renal tubular acidosis. This study is examining the safety and effectiveness of an extended-release form of alkali therapy (ADV7103) in maximizing alkali therapy over a 12-hour period and decreasing treatment to twice a day.

Support Groups – At this time, there is not a formal international- or United States-based support and advocacy group for primary distal renal tubular acidosis (primary dRTA). However, there are several Facebook pages focused on primary dRTA such as the ATP6V1B1 Renal Tubular Acidosis Kids with Hearing Loss Page, Renal Tubular Acidosis Page, and Parents of Children with Renal Tubular Acidosis. In addition, there are other support groups focused on specific symptoms of primary dRTA such as hearing loss and kidney (renal) disease. Examples of those include The National Kidney Foundation and My Child Without Limits, NORD, and ThinkGenetic.

dRTA Communities and Resources

Since its founding in 2007, Advicenne has been dedicated to developing and commercializing innovative treatments that address unmet medical needs in the area of nephrology. Our lead drug candidate, ADV7103, is in late-stage clinical trials for two indications: distal renal tubular acidosis (dRTA) and cystinuria. Listed on both the Euronext Paris and Euronext Brussels stock exchanges, the company is headquartered in Nîmes, France.

You are not alone. Connect with other members of the dRTA community on social media and with organizations providing education and support.