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PubMed This is a summary of 21 peer-reviewed journal articles Updated
Nephrology

Understanding the Causes: Is it Inherited or Acquired?

At a Glance

Distal renal tubular acidosis can be inherited from gene changes or acquired from autoimmune disease, medicines, toxins, urinary blockage, or urine backing up to the kidneys. Age of onset, medical history, blood and urine tests, and genetic testing help identify the cause and guide monitoring.

Distal renal tubular acidosis (dRTA) is not a “one size fits all” condition. Understanding why your kidneys are struggling to process acid is a critical step in your care. Doctors generally divide dRTA into two categories: inherited (passed down through families) and acquired (caused by another health issue or medication). While age is a strong clue—inherited forms usually present in childhood and acquired in adulthood—there are exceptions, and a careful medical evaluation is always needed.

Inherited dRTA: The Genetic Blueprint

Inherited dRTA occurs when there is a “typo” in the genetic instructions for the kidney’s acid pumps. This form is most commonly diagnosed in infants and children [1][2].

Several key genes are responsible for building the machinery that pumps acid out of the blood:

  • ATP6V1B1 and ATP6V0A4: These genes provide the blueprints for parts of the H±ATPase pump, the primary tool for moving acid into the urine [3][4]. These are usually autosomal recessive, meaning a child must inherit a faulty gene from both parents [5].
  • SLC4A1: This gene helps balance chloride and bicarbonate. Mutations here can be autosomal dominant (one faulty gene from one parent is enough) or recessive [5]. People with SLC4A1 mutations often develop symptoms later in childhood or even as young adults [6].
  • WDR72 and FOXI1: These are rarer genetic causes. WDR72 mutations are sometimes linked to amelogenesis imperfecta, a condition where tooth enamel is thin or abnormally formed [7].

Acquired dRTA: The “Secondary” Causes

In adults, dRTA is more likely to be an “acquired” condition, meaning the kidney’s acid pumps were working fine until they were damaged by another factor [1].

1. Autoimmune Diseases

The most common cause of acquired dRTA in adults is Sjögren syndrome, an autoimmune condition that often causes dry eyes and a dry mouth [8]. Interestingly, the kidney issues can sometimes appear before the dry mouth symptoms are even noticeable [9]. Other autoimmune links include:

  • Systemic Lupus Erythematosus (SLE) [10]
  • Rheumatoid Arthritis (RA) [11]
  • Autoimmune Thyroid or Liver Disease [12]

2. Medications and Toxins

Certain drugs can interfere with the distal tubule’s ability to handle acid. While rare, these may include some anti-inflammatory drugs (like 5-ASA) and even some newer cancer treatments called immune checkpoint inhibitors [13][14][15]. Always consult your prescriber before making any changes to your medication regimen.

3. Urological Issues

Long-term urinary tract issues, such as a severe blockage (obstruction) or urine backing up into the kidneys (vesicoureteral reflux), can eventually damage the delicate acid-pumping cells in the distal tubule [16][17].

The Role of Genetic Testing

While doctors can often diagnose dRTA through blood and urine tests, genetic testing offers a deeper level of insight. It can identify the exact “typo” in about 60% to 70% of pediatric cases [18][2]. It is important to note that a negative genetic panel does not definitively rule out a genetic cause, as some mutations remain undiscovered.

Why get tested?

  • Predicting Hearing Loss: Mutations in the ATP6V1B1, ATP6V0A4, and FOXI1 genes are strongly linked to sensorineural hearing loss [19]. If a child has these mutations, doctors will recommend regular hearing checks, as the loss can sometimes be progressive or appear later in life [20].
  • Family Planning: Knowing if a mutation is dominant or recessive helps families and genetic counselors understand the risk of passing the condition to future children [21].
  • Targeted Monitoring: If a WDR72 mutation is found, your team can coordinate with specialized dentists to protect tooth enamel early on [7].

Whether your dRTA is inherited or acquired, the goal remains the same: balancing your body’s chemistry to prevent long-term complications.

Common questions in this guide

How do doctors determine whether my distal renal tubular acidosis is inherited or acquired?
Doctors consider when symptoms began, family history, associated findings, and whether you have an autoimmune disease, medication exposure, or urinary tract problem. Inherited forms often appear in infancy or childhood, while acquired forms are more common in adults, but age alone cannot determine the cause. Blood and urine tests, and sometimes genetic testing, help complete the evaluation.
Which gene changes can cause inherited dRTA?
Inherited distal renal tubular acidosis can result from changes in ATP6V1B1, ATP6V0A4, SLC4A1, WDR72, or FOXI1. Some forms require a changed copy from both parents, while SLC4A1-related disease can be dominant or recessive. The exact gene can help doctors plan hearing, dental, and family counseling follow-up.
Could Sjögren syndrome cause dRTA before dry mouth or dry eyes?
Yes. Kidney involvement related to Sjögren syndrome can sometimes appear before noticeable dry mouth or dry eyes. Adults with distal renal tubular acidosis may need evaluation for Sjögren syndrome and other autoimmune conditions based on their history and test results.
What can genetic testing tell me if I have dRTA?
A genetic panel may identify the specific gene change responsible for dRTA and can clarify inheritance and risks for relatives or future children. It can also help guide monitoring for hearing loss or dental enamel problems. A negative panel does not completely rule out a genetic cause because some disease-causing changes may not yet be known or detected.
Why might someone with inherited dRTA need hearing tests?
Changes in ATP6V1B1, ATP6V0A4, and FOXI1 are associated with sensorineural hearing loss, which can progress or appear later. A baseline hearing evaluation and regular follow-up may help identify changes early, especially in children with one of these gene changes.
What health problems or medicines can lead to acquired dRTA?
Acquired distal renal tubular acidosis can be associated with autoimmune diseases such as Sjögren syndrome, lupus, rheumatoid arthritis, or autoimmune thyroid or liver disease. Some anti-inflammatory medicines, immune checkpoint inhibitors, severe urinary blockage, and urine backing up toward the kidneys can also affect acid handling. Do not stop or change a prescribed medicine without speaking with the prescriber.

Questions For You

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Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Given my symptoms and age of onset, do you suspect my dRTA is genetic or acquired from another condition?
  2. 2.If we pursue genetic testing, will it be a comprehensive panel that covers genes like ATP6V1B1, ATP6V0A4, and SLC4A1?
  3. 3.Since certain genes are linked to hearing loss, should I or my child have a baseline audiology (hearing) test?
  4. 4.For adults: Should we screen for Sjögren’s syndrome or other autoimmune diseases even if I don't have a dry mouth or dry eyes?
  5. 5.How does knowing the specific gene mutation help us predict or monitor for other issues, like dental enamel problems or bone health?

References

References (21)
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    The genetic and clinical spectrum of a large cohort of patients with distal renal tubular acidosis.

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This page about inherited and acquired distal renal tubular acidosis is for informational purposes only and does not constitute medical advice. Ask your nephrologist or genetics team to interpret your tests and discuss medication changes, genetic results, and monitoring.