What Is Renal Tubular Acidosis?

Renal tubular acidosis (RTA) is a clinical syndrome in which the kidneys are unable to get rid of enough acid, retain enough base, or both. Renal tubular acidosis can be divided into different subtypes, each with its own characteristics. It is often discovered with blood testing, and early diagnosis can help healthcare providers prevent complications from prolonged kidney dysfunction.

RTA and the Kidneys

The kidneys are critical in maintaining the balance of acid and base in the body. Under usual conditions, the body is constantly generating acid, mainly via the breakdown of proteins.

Normally, the kidney excretes excess acid into the urine. A disruption of this process leads to the accumulation of acid in the blood known as metabolic acidosis.

To understand renal tubular acidosis, it is necessary to understand a little about renal (kidney) physiology. The smallest functional unit of the kidney is called a nephron, and each kidney is made up of about one million of them.

Each nephron is a tiny, extremely fine tubule. One end of the tubule is folded into a cuplike structure, which surrounds a cluster of tiny blood vessels called the glomerulus. Blood is filtered as it passes through the glomerulus and enters the tubule of the nephron.

A tubule can be divided into two parts. The filtered blood (filtrate) first enters the proximal tubule and then passes into the distal tubule. As it passes through the proximal and distal tubules, the kidney secretes certain substances into it and re-absorbs other substances back into the bloodstream. The final product is urine, which is carried away from the kidney into the bladder.

In the proximal tubule, bicarbonate (a base, the opposite of acid) is reabsorbed from the filtrate back into the bloodstream. In the distal tubule, acid is secreted from the blood directly into the filtrate and carried off in the urine. If either one of these processes is disturbed, metabolic acidosis is the result.

Types and Causes of Renal Tubular Acidosis

Renal tubular acidosis is divided into three or four subtypes; experts differ on how exactly to categorize them. A common way to describe RTA relies on which part of the tubule is malfunctioning:

• Type 1 (distal) RTA
• Type 2 (proximal) RTA
• Type 4 RTA (or hypoaldosteronism-associated RTA)

Type 3 RTA is a term that is now rarely used by healthcare providers. It combines characteristics of types 1 and 2 and is associated with the dysfunction or deficiency of an important enzyme called carbonic anhydrase. It has also been used to describe the temporary RTA, which may occur in young children whose nephron function has not fully matured.

Type 1 (Distal) RTA

As the name suggests, type 1 or distal RTA implies a problem in the distal tubule of the nephrons and is characterized by a failure of the nephrons to secrete enough acid into the urine.

Type 1 RTA usually occurs in association with another illness, and there is a long list of conditions that can affect the nephrons in such a way as to cause type 1 RTA. This includes inherited diseases such as sickle-cell anemia, Marfan syndrome, Wilson's disease, and Ehlers-Danlos syndrome. It also includes autoimmune diseases such as lupus, rheumatoid arthritis, and Sjögren's syndrome. Diseases of the renal tissue, including medullary nephrocalcinosis, may also cause type 1 RTA.

Type 1 RTA may be associated with certain medications, such as lithium or amphotericin B. Type 1 RTA can also be seen after renal transplantation due to chronic rejection.

Type 2 (Proximal) RTA

Type 2 RTA is characterized by a failure of the nephrons to reclaim enough base from the filtered blood. Too much base is lost in the urine, and the blood becomes too acidic (metabolic acidosis). Because this process occurs mostly in the proximal tubule, type 2 RTA is also called proximal RTA.

Type 2 RTA is the least common form of RTA and, like type 1 RTA, usually does not occur in isolation, but is associated with another disorder. Once again, there is a long list of diseases that may cause type 2 RTA.

Hereditary disorders which may cause type 2 RTA include Fanconi syndrome, Wilson's disease, tyrosinemia, fructose intolerance, or type 1 glycogen storage disorders.

Acquired conditions that may cause type 2 RTA include heavy metal poisoning, use of the medication acetazolamide, or multiple myeloma.

Type 4 RTA (hyperaldosteronism-associated RTA)

Type 4 RTA is characterized by a deficiency of the hormone aldosterone or by a failure of kidney cells to respond to it.

Aldosterone signals the kidney to retain sodium or get rid of potassium. If there is too little of the hormone, or if the kidney cells do not respond normally to it, the kidney does not excrete enough potassium into the urine. This causes an increase in potassium levels in the body—a condition called hyperkalemia.

Hyperkalemia slows down the production of ammonia, which is an important base which allows acid to be carried away in the urine. Metabolic acidosis is the result.

Aldosterone is secreted by the adrenal glands and production is stimulated by the kidneys. Chronic kidney disease due to diabetes or other conditions can disrupt aldosterone levels and cause type 4 RTA.

Diseases that affect the function of the adrenal glands can also interfere with aldosterone production and result in type 4 RTA. Rarely, inherited conditions may result in low aldosterone levels or resistance to the action of aldosterone.

Many medications can cause type 4 RTA through various mechanisms. These include nonsteroidal anti-inflammatory drugs (NSAIDs), immunosuppressants (such as cyclosporine), angiotensin inhibitors, heparin, certain diuretics (such as spironolactone), and certain antibiotics (trimethoprim and pentamidine).

Renal Tubular Acidosis Symptoms

Patients with RTA may come to medical attention as infants, older children, or adults. Since there are different types of RTA with a variety of inherited and non-inherited (acquired) causes, the symptoms of the syndrome can be variable. In adults, RTA is usually the result of some other disease, and symptomatology may be determined by the underlying disorder.

Children with type 1 and type 2 RTA often present with growth abnormalities. In type 1 RTA, kidney stones are a common problem. In patients with type 1 RTA caused by an underlying disease (such as sickle cell disease or Marfan syndrome), the clinical picture is often dominated by that disease.

Children with RTA due to certain hereditary conditions may come to medical attention for deafness, bone abnormalities, eye problems, or intellectual disabilities.

The symptoms of type 4 RTA are usually fairly mild. Because this type is usually associated with high potassium levels, healthcare providers may have to take action to increase the excretion of potassium or limit potassium intake.

In general, healthcare providers may suspect that you may have renal tubular acidosis if you have recurrent kidney stones (especially if you have a long family history of stones). Your healthcare provider may also suspect RTA if you or your child has certain unexplained bone abnormalities (osteomalacia or osteopetrosis), or if you have autoimmune disease (such as Sjögren's syndrome) with metabolic acidosis. Patients with unexplained metabolic acidosis may also be evaluated for RTA.

Diagnosis

The diagnosis of RTA depends on your medical history and on the results of simple blood and urine tests. Your healthcare provider may check your blood for electrolyte levels, particularly sodium, potassium, chlorine, and bicarbonate.

Occasionally, an arterial blood sample may be required to confirm that you have metabolic acidosis. Your healthcare provider may also check your urine for acidity and levels of ammonia and other electrolytes. If type 4 RTA is suspected, the levels of blood aldosterone and related hormones may be checked.

Some patients with RTA may have relatively mild blood and urine abnormalities. "Provocative" tests may be performed to see whether your kidneys can normally excrete ingested acids.

Historically, healthcare providers have given a mildly acidic oral solution (ammonium chloride) and then checked urine acidity. Healthcare providers may also give a dose of steroids, diuretics, or salt solution to see if your kidneys respond normally by excreting more acids.

In some situations, your healthcare provider may administer IV bicarbonate and test urine acidity. This can help distinguish between type 1 and type 2 RTA.

Treatment

Treatment of RTA is based on the administration of base (bicarbonate or citrate, usually) to neutralize excess blood acid or to replace bicarbonate loss in the urine. If administered bases are not effective, thiazide diuretics (such as hydrochlorothiazide) may be required.

Administering base is often enough to reverse bone abnormalities, allow the resumption of normal growth, and stop the formation of kidney stones. However, deafness associated with certain inherited conditions may be irreversible.

If the RTA is related to another illness, such as lupus, treatment of the underlying disease may improve the acidosis. RTA caused by medications may require cessation of the offending drug.

Type 4 RTA may require treatment with steroid hormones (such as fludrocortisone or Florinef) to act in place of the deficient aldosterone. Potassium supplementation may be required for patients with associated low potassium, while potassium lowering treatments may be needed in patients with high potassium.

Regardless of the treatment regimen, adherence to therapy is critical to prevent the complications of prolonged RTA. For example, kidney stone formation, if uncontrolled, can eventually lead to chronic kidney failure requiring dialysis.