What Is Renal Tubular Acidosis?
Renal tubular acidosis (RTA) is characterized by the accumulation of acid in the body due to the failure of the kidneys to remove acid from the blood into the urine. This, in turn, results in an increased acid level in the blood, causing acidosis.
What Are the Types of Renal Tubular Acidosis?
There are four subtypes of renal tubular acidosis, it includes:
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Type 1 (Distal Renal Tubular Acidosis) - It is caused due to a problem in the distal part or end of the tubules of the kidney.
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Type 2 (Proximal Renal Tubular Acidosis) - It is caused due to the problem at the beginning of the proximal part of the tubules of the kidney.
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Type 3 (Mixed Renal Tubular Acidosis) - It is reported to be the combination of type 1 and type 2 distal renal tubular acidosis.
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Type 4 (Hyporeninemic Renal Tubular Acidosis).- Also known as hyperkalemic RTA, it occurs when the tubules of the kidneys are not able to remove the potassium from the blood.
What Is the Etiology of Renal Tubular Acidosis?
All the four subtypes of renal tubular acidosis share different etiologies, it includes:
Type 1: Distal Renal Tubular Acidosis
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Systemic Lupus Erythematosus (SLE) - This is an autoimmune disease characterized by the production of antibodies against the body's cells.
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Systemic Sclerosis - Is characterized by vascular abnormalities and diffuse fibrosis of the skin, joints, etc.
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Genetic Mutations - Affecting tubular functions.
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Marfan Syndrome - This is an inherited connective tissue disorder.
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Ehlers Danlos Syndrome - This is a group of connective tissue disorders affecting the joints, skin, etc.
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Sickle Cell Disease - This is a red blood cell disorder characterized by the sickling of the red blood cells affecting their function.
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Medullary Sponge Kidney - This is a congenital defect characterized by the cystic dilatation of the tubules of the kidney.
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Obstructive Uropathy - It is characterized by the inability of the kidneys to drain the urine through the urinary tract.
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Renal Transplant Rejection is an abnormal immune reaction by the body due to kidney transplantation.
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Multiple Myeloma - This is a cancerous condition affecting the plasma cells.
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Certain Drugs - Drugs like Amphotericin B, NSAIDs (nonsteroidal anti-inflammatory drugs), Lithium, etc.
Type 2: Proximal Renal Tubular Acidosis.
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Multiple Myeloma is a form of white blood cell (WBC) tumor.
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Amyloidosis - This is a group of diseases characterized by the deposition of amyloid in various body organs.
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Inherited Disorders - Certain genetic disorders, like sickle cell disease, etc., may lead to renal tubular acidosis.
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Drugs - Such as Tetracyclines, Aminoglycosides, mercury, Tenofovir, etc.
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Autoimmune Disorders - Sjogren's syndrome, SLE.
Type 3: Mixed Renal Tubular Acidosis.
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Genetic Mutations - Mutation in the carbonic anhydrase II would result in this type of RTA.
Type 4: Hyporeninemic Renal Tubular Acidosis.
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Autoimmune Disorders such as Sjogren's syndrome, SLE, etc.
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Drugs - Drugs such as NSAIDs, beta-blockers,potassium-sparing diuretics, etc.
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Hyporeninemic Hypoaldosteronism - It is a mineralocorticoid deficiency characterized by decreased serum aldosterone levels.
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Sickle Cell Disease is a red blood cell (RBC) disorder that causes pain, swelling in the hands and feet, and other symptoms of anemia.
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Chronic Obstruction of the Urinary Tract.
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Interstitial Nephritis - This is a disorder of the kidney characterized by the inflammation of the spaces between the kidney tubules.
What Is the Pathophysiology of Renal Tubular Acidosis?
Type 1: Distal Renal Tubular Acidosis
Distal tubules of the kidney are responsible for the generation of bicarbonate which prevents the blood from becoming too acidic.
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Any type of damage to the alpha-intercalated cells of the distal tubules would affect the generation of bicarbonates and result in acidic urine. It may also cause reduced sodium reabsorption, which would end up in decreased secretion of potassium and protons.
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Decreased functioning of H-ATPase can be seen in conditions like Amphotericin B toxicity leading to an increased leak of protons from the tubules.
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Autosomal dominant mutations in the SLC4A1 gene are located in chromosome 17q 21- q22 codes for chloride bicarbonate exchanger.
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Autosomal recessive with deafness with mutations in the gene ATP6V1B located in chromosome 2p13. It is expressed in the alpha-intercalated cells of the distal tubules and in the cochlear region.
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Autosomal recessive without deafness with mutations in the gene ATP6V0A4 located in chromosome 7q33-q34.
Type 2: Proximal Renal Tubular Acidosis.
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Proximal tubules of the kidney are involved in reabsorbing 85 to 90 % of bicarbonate. The above-said etiologies increase the chances of bicarbonate leak resulting in increased loss of bicarbonates in the urine. Due to the decreased bicarbonate reabsorption in the proximal tubules, there would be osmotic diuresis leading to hypokalemia (decreased serum potassium levels).
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The mutation in the SLC4A4 gene that codes for the sodium bicarbonate cotransporter would also result in this type of RTA as it results in decreased bicarbonate reabsorption in the proximal tubules.
Type 3: Mixed Renal Tubular Acidosis.
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It is due to the mutation of the carbonic anhydrase II enzyme located in chromosome 8q22. This results in the occurrence of a combination of type 1 and 2 RTA.
Type 4 : Hyporeninemic Renal Tubular Acidosis.
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This type occurs mainly due to the decreased availability of ammonia which is a principal buffer in the urine. Hyperkalemia (increased potassium levels in the blood) caused due to the above-said etiologies would impair the production of ammonia in the proximal tubules. This would result in a decreased amount of ammonia available to buffer the urine causing the symptoms of the disease.
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Other causes like NSAIDs, beta-blockers, potassium-sparing diuretics, etc., would indirectly contribute to the development of type 4 RTA by resisting the action of aldosterone, thereby causing hyperkalemia and its manifestations.
What Are the Risk Factors of Renal Tubular Acidosis?
The risk factors include:
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Autoimmune Diseases - Patients with autoimmune diseases such as Sjogren's syndrome (which is characterized by the autoantibodies against their own body cells leading to dry eye and dry mouth) and systemic lupus.
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Fanconi Syndrome - It is characterized by the release of certain components absorbed by the kidneys in the urine.
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Viral Hepatitis - It is the inflammation of the liver as a result of a viral infection.
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Hyperaldosteronism - Decreased serum aldosterone levels.
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Multiple Myeloma - This is a cancerous condition affecting the plasma cells of the body.
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Immunosuppressive Medications - Such as steroids, Colchicine, etc., are reported to be the risk factors for this condition.
What Are the Signs and Symptoms of Renal Tubular Acidosis?
The signs and symptoms of types 1, 2, and 3 differ from type 4 RTA as in the former types; the symptoms occur due to the low levels of bicarbonate and potassium in the blood, whereas in type 4, it is due to the low bicarbonate and high potassium in the blood.
Symptoms of types 1, 2, and 3 (due to low potassium and bicarbonate levels) include:
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Weakness.
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Paralysis.
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Bradycardia (slow heartbeat).
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Osteomalacia (softening of the bones).
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Cerebral calcifications (calcifications in the cerebrum of the brain).
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Growth failure.
Symptoms of type 4 (due to high potassium and low bicarbonate levels) include:
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Muscle weakness.
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Loss of appetite.
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Fatigue.
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Abdominal pain.
How Is Renal Tubular Acidosis Diagnosed?
The steps in diagnosis include:
1) Medical and Family History: A thorough medical and family history of the patient is important as it plays a vital role in diagnosing the cause of the condition. Medical history, such as the preexisting autoimmune disorders, the associated symptoms of the condition, and the family history to know the genetic link or any related persons suffering from the same disorder would help in the effective management of the condition.
2) Clinical Examination: The clinical examination would help to check for the signs of the condition as well as the underlying diseases such as dry mouth, dry skin, skin lesions, growth failure, bone defects, etc.
3) Blood Test:
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Serum Bicarbonate Levels - Serum bicarbonate levels are altered in different types in type 1 - 10 to 20 mEq/L, type 2 - 12 to 18 mEq/L, and type 4 - greater than 17 mEq/L.
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Serum Chloride Levels - This would indicate increased chloride concentration.
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Blood pH - This would reveal the decreased pH indicating metabolic acidosis.
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Serum Potassium Levels - It is low in types 1, 2, and 3 and high in type 4.
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Blood Urea Nitrogen and Creatinine Levels - Shows normal levels, indicating normal renal function.
4) Urine Test:
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Urinary pH - In type 1, the pH is greater than 5.5, and in types 2 and 4, it shows a pH of less than 5.5.
5) Acid Load Test: In this test, acid is infused into the blood with 100 mg/kg of ammonium chloride, and the pH of the urine and plasma bicarbonate levels should be monitored once in three hours. In healthy individuals, the infused acid will get excreted completely with restored normal urine pH. In the case of patients with type 1 RTA, the urine pH will be greater than 5.5.
6) Bicarbonate Infusion Test: Bicarbonate is infused into the blood, and the fractional excretion of bicarbonate is measured. In the case of patients with type 2 RTA, the urine pH increases because of the presence of excessive bicarbonate in the urine.
How Is Renal Tubular Acidosis Managed?
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Oral Bicarbonate Replacement - It would help in compensating for the reduced bicarbonate levels at a rate of 1 to 2 meq/kg per day. High doses of more than 10 mmol/kg per day are required for treating type 2 RTA.
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Oral Potassium Citrate - Is given in patients with hypokalemia.
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Oral Phosphate and Vitamin D Supplements - Are given to treat decreased phosphate levels and vitamin D deficiency.
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Thiazide Diuretics - This would help in enhancing bicarbonate reabsorption in the proximal tubules.
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Fludrocortisone - It is used to treat hypokalemia associated with hypoaldosteronism.
Conclusion:
A renal tubular acidosis is a group of conditions called non-anion gap hyperchloremic metabolic acidosis. The complications would occur as a result of the acidic pH of the blood. The underlying cause of the condition should be diagnosed early, and treatment should be initiated as early as possible to prevent further complications.