What is Renal Tubular Acidosis?
The kidneys perform a really crucial function in your body, working in harmony with the lungs to keep the balance of acids and bases in check. They do this by taking in bicarbonate, a vital compound for neutralizing acid, and getting rid of extra hydrogen ions, which can increase acidity. When the kidneys struggle with handling these acids, especially when their general functions are relatively fine, we refer to this as renal tubular acidosis. In simpler terms, this is when your kidneys can’t balance the acidity in your body properly, and this results in a specific type of imbalance in the body’s chemistry.
Renal tubular acidosis isn’t just one condition, but has four different types or subtypes. Each of these deal with a different part of the kidney’s job in managing body’s acid and base balance. For instance, the kidneys reabsorb bicarbonate primarily by trading it with sodium and hydrogen, and this accounts for around 85% to 90% of the body’s acid regulation. Additionally, the kidneys get rid of hydrogen ions and produce a substance called NH3, which is a major component of urine and helps to control acidity.
The subtypes of renal tubular acidosis are:
1. Type 1: Distal RTA, which affects the part of the kidney farthest from its starting point.
2. Type 2: Proximal RTA, which affects the part of the kidney nearest to its starting point.
3. Type 3: Mixed RTA, involving elements of both the previous types.
4. Type 4: Hyporeninemic hypoaldosteronism RTA, which is caused by low levels of two important hormones.
What Causes Renal Tubular Acidosis?
Type 1 Distal renal tubular acidosis (RTA) is mostly caused by autoimmune diseases in adults. These diseases include Lupus, Sjogren’s syndrome, rheumatoid arthritis, thyroiditis, and a few others. It can also be inherited due to genetic mutations. Sometimes, genetic conditions like Marfan syndrome or sickle cell disease can also cause it. Nephrocalcinosis, chronic changes in the kidney due to calcium deposit, or chronic kidney diseases can also lead to Type 1 Distal RTA. Certain drugs like lithium, NSAIDs, and a few others can cause it too.
Type 2 Proximal RTA often occurs due to an excess of proteins in the blood, a condition called hypergammaglobulinemia. This is often seen in adults. Certain inherited genetic mutations can also cause it. There are specific drugs that can induce Type 2 Proximal RTA – these include heavy metals, certain inhibitors, and outdated antibiotics, among others. Some autoimmune diseases like Systemic lupus erythematosus, also known as SLE or lupus, can also cause it.
Type 3 Mixed RTA is generally caused by inherited mutations in a specific enzyme in our body known as carbonic anhydrase II.
Type 4 Hyperkalemic RTA is often caused by a condition called hyporeninemic hypoaldosteronism where the adrenal glands don’t produce enough of certain hormones. Diabetic nephropathy, a complication of diabetes harmful to your kidneys, is the most common cause in adults. Certain medications, autoimmune diseases, and genetic conditions can also cause it. Sometimes, chronic kidney diseases or obstructions in the urinary tract can cause Type 4 Hyperkalemic RTA.
Risk Factors and Frequency for Renal Tubular Acidosis
Renal tubular acidosis (RTA) and its major types are infrequent. Mostly, these cases go undiagnosed, especially those with incomplete RTA. Inherited forms of RTA are even less frequent than acquired ones. The most prevailing type worldwide and in the U.S. is type 4 hyperkalemic RTA, primarily caused by diabetes damaging the kidneys, which leads to hyporeninemic hypoaldosteronism, and urinary tract blockage. Also, post kidney transplant patients have a risk of over 20% to develop RTA due to rejection or the use of immunosuppressive drugs.
- Type 2 Proximal RTA is less common than Type 1 Distal RTA.
- Fanconi syndrome is extremely infrequent as a primary disease.
- Fanconi syndrome occurs alongside several diseases, such as Wilson disease, cystinosis, galactosemia, hereditary fructose intolerance, and von Gierke disease, which all are rare.
- RTA can be linked with certain medications like antivirals used for treating HIV and viral hepatitis, and its occurrence is on the rise.
- Type 3 Mixed RTA is an extremely rare inherited disease, commonly found in children with Arabic, North African, and Middle Eastern backgrounds.
Signs and Symptoms of Renal Tubular Acidosis
Distal Type 1, Proximal Type 2, Mixed Type 3, and Hyperkalemic Type 4 are different forms of Renal Tubular Acidosis (RTA), a condition where kidneys can’t properly remove acids from the blood into the urine. Here’s a layman breakdown of what characterizes each type:
- Type 1 Distal: Features include weak, softened bones (Rickets), poor growth, and metabolic acidosis (excess acid in the body) which can lead to kidney stones and urinary tract infections. Patients may also develop muscle weakness and heart rhythm problems due to low potassium levels.
- Type 2 Proximal: Chronic acid imbalance in the body can weaken the bones and lead to loss of potassium in the urine. Other consequences include loss of phosphate (leading to Rickets), glucose, urate, and amino acids in the urine.
- Type 3 Mixed: Known as Guibaud-Vainsel syndrome or marble brain disease, it’s characterized by hardened bones, mixed type of RTA, cerebral calcification (a buildup of calcium in the brain), and mental retardation. Other symptoms include bone fractures from increased bone fragility and poor growth. It may also cause abnormal facial bone growth leading to facial deformation and potential loss of sight or hearing from nerve compression.
- Type 4 Hyperkalemic: This type differs from the others as it results in high potassium levels due to an aldosterone deficiency, a hormone that helps regulate sodium and potassium levels. A mild form of metabolic acidosis is also present.
Testing for Renal Tubular Acidosis
If your doctor suspects that you might have a medical condition known as Renal Tubular Acidosis (RTA), which affects how your kidneys maintain acid levels in the body, they might conduct several tests. These tests could include measuring the pH level in your blood and examining the levels of bicarbonate, chloride, and potassium in your blood and urine.
RTA can be classified into three main types, each presenting different bicarbonate levels:
* Type 1: Bicarbonate levels are usually between 10 to 20 mEq/L.
* Type 2: Bicarbonate levels normally range from 12 to 18 mEq/L.
* Type 4: Bicarbonate levels are generally more than 17 mEq/L.
Further tests, such as plasma potassium and BUN/Cr, can help determine the type of RTA.
In type 1 and type 2, you typically have low potassium levels in your blood. However, in type 4, your potassium levels tend to be high.
As for BUN/Cr tests, it measures your blood urea nitrogen and creatinine. Normal or near-normal results from these tests could rule out kidney failure as the cause of the acid buildup.
One of the key tests is the urinalysis. This test checks how acidic or alkaline your urine is. In type 1 RTA, despite the buildup of acid in your body, your urine pH is typically high. The same applies to type 2 RTA if your bicarbonate levels are high. But in types 2 and 4, your urine tends to be acidic.
Another test your doctor might perform is the urine culture. This test can help rule out a urinary tract infection that could be causing a high urine pH.
The urine anion gap test is another crucial test primarily used to determine the cause of acid buildup in your body. A positive gap indicates reduced NH4Cl (ammonium chloride) excretion in your urine, aligning with the symptoms of RTA.
Finally, your doctor might perform specific tests like the Acid Load Test and Bicarbonate Infusion Test. These tests can confirm the presence of RTA and help identify its type.
For example, in the Acid Load Test, your doctor infuses your blood with ammonium chloride and checks how well your body excretes acid. If your urine pH doesn’t lower as your blood becomes more acidic, that could indicate type 1 RTA.
In the Bicarbonate Infusion Test, your doctor will infuse bicarbonate into your blood and monitor how it’s excreted by your kidneys. If a significant amount of bicarbonate appears in your urine after the infusion, it may suggest type 2 RTA.
With type 4 RTA, even after following a low-sodium diet, you may still have high levels of sodium in your urine. This condition often happens due to aldosterone deficiency or resistance. Aldosterone is a hormone that helps regulate the amount of sodium in your body.
Treatment Options for Renal Tubular Acidosis
Chronic acidemia is a condition where there’s too much acid in your body fluids. When left unchecked, it can harm your bones and muscles. One way doctors treat this is through the administration of alkali, a substance that neutralizes the acid. Sodium bicarbonate and potassium citrate, which are types of alkali, are usually given orally in a daily dosage. Potassium citrate may be preferred for patients with low potassium levels, kidney stones, or calcium deposits in the kidneys. It’s also key to acknowledge and treat any underlying conditions causing acidemia.
Our bodies predominantly absorb bicarbonate, a component of the alkali medication, in the proximal tubule – a part of the kidney. Meaning, it’s usually easy to correct distal RTA, a form of renal tubular acidosis that affects a different part of the kidney. The proximal tubule can absorb the bicarbonate you ingest and help correct acidemia.
To treat type 2 RTA, a condition in which the kidney doesn’t properly remove acid from the body, larger doses of bicarbonate are needed. Increasing the bicarbonate concentration in your blood also increases urinary potassium losses. For this reason, potassium salts are usually given to reduce low potassium levels (hypokalemia) that can come with alkali therapy. Thiazide diuretics, a type of medication that helps your kidneys expel more water and sodium, is used to promote bicarbonate reabsorption in type 2 RTA.
Some patients may also experience low levels of phosphate in the blood, or hypophosphatemia. This is due to reduced proximal phosphate reabsorption and less active vitamin D. Both of these can contribute to bone disease. To combat this, doctors may prescribe both phosphate and vitamin D supplements to normalize phosphate levels in the blood and reverse bone disease.
Lastly, fludrocortisone is a medication that can effectively control high potassium levels in the blood, a condition known as hyperkalemia, which is associated with a deficiency of the hormone aldosterone. However, use of this medication may not be common because it can cause high blood pressure, heart failure, and fluid build-up, especially in patients with kidney issues. Patients usually manage high potassium levels by limiting their daily potassium intake through their diet and, if required, using certain types of diuretics (loop or thiazide) to enhance potassium excretion.
What else can Renal Tubular Acidosis be?
- Cystinosis
- Ehlers-Danos Syndrome
- Multiple Myeloma
- Pseudohypoaldosteronism
- Pyruvate Carboxylase deficiency
- Sjorgren Syndrome
- Systemic Lupus Erythematosus
- Tyrosinemia
- Wilson disease
