Renal Tubular Acidosis Definition
Renal Tubular Acidosis (RTA) is a type of medical condition that is characterized by accumulation of acids in the body caused by failure or inability of the kidneys to acidify the urine appropriately. When the kidney filters the blood, the filtrate is passed through the nephron’s tubules which allow the exchange of acid equivalents, salts as well as other solutes before it passes off into bladder as urine. This metabolic acidosis which results from renal tubular acidosis might be either caused by a failure to recover the alkaline bicarbonate ions from filtrate in early parts of the nephron or proximal tubule or by an insufficient secretion of the acid hydrogen ions in the latter parts of the nephron or distal tubule.
Renal Tubular Acidosis Epidemiology
All forms of RTA are uncommon. However, it is difficult to trace the exact rate of prevalence of these conditions as they are often under-reported and the incomplete forms are frequently not recognized. The inherited forms of RTA are even rarer than the acquired forms.
Renal Tubular Acidosis Types
There are mainly four types of RTA, which are listed below:
Type 1 or Distal renal tubular acidosis
Distal RTA or dRTA is said to be the classical form of the condition. It is characterized by failure to secrete acid by alpha intercalated cells that make up the cortical collecting duct of distal nephron.
Type 2 or Proximal renal tubular acidosis
Proximal RTA or pRTA occurs due to a failure of proximal tubular cells to re-absorb the filtered bicarbonate from urine. This leads to urinary bicarbonate wasting and thereby, subsequent academia. As the distal intercalated cells are able to function normally, the acidemia is much less severe than in the case of Distal RTA. The urine is able to acidify to pH level less than 5.3.
Type 3 or Combined proximal and distal renal tubular acidosis
In some cases, RTA is found to exhibit features that are common to both distal and proximal variants of the condition. This disorder was first observed in children and infants having dRTA during the 1960s and 70s as a sort of transient phase. Sometimes, it is also referred to as the juvenile variant of RTA.
Type 4 or Hyperkalemic renal tubular acidosis
It is not a tubular disorder like the other types of RTA, nor is it characterized by clinical syndrome like the other forms of RTA. However, it is still included within the classification of RTA due to its link with a mild metabolic acidosis caused by physiological reduction in the proximal tubular ammonium excretion or impaired ammoniagenesis. It is secondary to the condition of hypoaldosteronism and leads to reduced urine buffering capacity. The condition is also known as tubular hyperkalemia.
Renal Tubular Acidosis Causes
The four different types of RTA are caused by a variety of factors. These are listed below:
Distal renal tubular acidosis
The common factors causing distal RTA are:
- Amyloidosis
- Fabry disease
- Liver cirrhosis
- Sickle cell anemia
- Renal transplantation
- Chronic obstruction of the urinary tract
- Toxins such as ifosfamide, toluene, amphotericin B and lithium carbonate
- It can occur as a possible after effect of the IV-administered bisphosphonates like zoledronate (~10%)
- Nephrocalcinosis, which can be both a sign as well as a cause, and is related to the calcium-induced damage of cortical collecting duct
- Autoimmune diseases, such as the classic Sjögren’s syndrome, rheumatoid arthritis, systemic lupus erythematosus and hypergammaglobulinemia
- Hereditary causes may include mutations of the Band 3, which acts as a basolateral bicarbonate transporter for the intercalated cell. It can be inherited in an autosomal dominant pattern as seen in the western European instances, or in an autosomal recessive pattern as seen in the cases reported in South East Asia. Other genetic factors include mutations of the subunits of apical proton pump vH+-ATPase that is transmitted in autosomal recessive pattern. It might be associated with the symptoms of sensorineural deafness.
Proximal renal tubular acidosis
A number of genetic or familial disorders, as well as acquired conditions, might be responsible for the development of this condition which is mentioned below:
Genetic conditions
The genetic or familial factors responsible for pRTA include:
- Cystinosis
- Tyrosinemia
- Galactosemia
- Lowe syndrome
- Wilson’s disease
- Fanconi Syndrome
- Hereditary fructose intolerance
- Glycogen storage disease (type I)
Acquired conditions
The acquired or environmental causes that lead to pRTA consist of:
- Paroxysmal nocturnal hemoglobinuria
- Amyloidosis
- Multiple myeloma
- Vitamin D deficiency
- Primary hyperparathyroidism
- Toxins, like HAART, lead, ifosfamide, and cadmium
- Drugs like acetazolamide, outdated tetracycline or aminoglycoside antibiotics
Combined proximal and distal renal tubular acidosis
Combined proximal and distal RTA is caused by an inherited or familial carbonic anhydrase II deficiency.
Hyperkalemic renal tubular acidosis
Hyperkalemic RTA is mainly caused by aldosterone-related conditions, certain drug reactions as well as health conditions that alter the structure of the kidney. The common underlying factors for this condition include:
- HIV/AIDS
- Amyloidosis
- Sickle cell disease
- Addison’s disease
- Diabetic nephropathy
- Aldosterone resistance
- Urinary tract obstruction
- Kidney transplant rejection
- Pseudohypoaldosteronism
- Systemic lupus erythematosus
- Heparin, which keeps the blood from clotting
- Aldosterone deficiency or hypoaldosteronism
- Removal and/or destruction of both the adrenal glands
- Blood pressure drugs like angiotensin receptor blockers and ACE inhibitors
- Drugs like diuretics, NSAIDs, certain antibiotics and immunosuppressive drugs
Renal Tubular Acidosis Symptoms
The general signs and symptoms of the condition may vary from one patient to another and depends on the type of RTA that affects a sufferer. The common signs of each type of RTA are described below:
Distal renal tubular acidosis
Although some cases of dRTA are asymptomatic, most patients tend to have the following symptoms:
- Fatigue
- Confusion
- Hypokalemia
- Impaired growth
- Muscle weakness
- Increased rate of breathing
- Increased aldosterone levels
- Normal anion gap metabolic acidosis or acidemia
- Nephrocalcinosis or calcium deposition in the renal substance
- Bone demineralization leading to rickets in children and infants as well as osteomalacia in adults
- Formation of urinary stones that is related to low urinary citrate, hypercalciuria, and alkaline urine
Proximal renal tubular acidosis
The general signs and symptoms of pRTA include:
- Rickets
- Fatigue
- Weakness
- Muscle pain
- Dehydration
- Osteomalacia
- Muscle cramps
- Skeletal deformities
- Decreased urine output
- Increased breathing rate
- Confusion or reduced alertness
- Pain in the back, bones, flank, or abdomen
- Increased heart rate and/or irregular heartbeat
Combined proximal and distal renal tubular acidosis
The common features of the combined variant of RTA include the signs and symptoms that characterize distal and proximal RTA, as well as the following:
- Osteopetrosis
- Mental retardation
- Cerebral calcification
Hyperkalemic Renal Tubular Acidosis
The cardinal feature of the Type 4 RTA is hyperkalemia. The condition is commonly asymptomatic. However, if severe hyperkalemia develops, it might lead to muscle weakness and life-threatening arrhythmia. Acidosis is normally mild and asymptomatic. Other features commonly ascribed to this disorder include:
- Diabetes mellitus
- High blood acidity
- High blood potassium
- Chronic renal insufficiency
- High levels of blood potassium
Renal Tubular Acidosis Diagnosis
The diagnosis of RTA is carried out by evaluating the blood chemistries and the arterial blood gas which may suggest electrolyte imbalances or metabolic acidosis, and show lower levels of potassium and/or bicarbonate. Other tests that are conducted to evaluate this condition include:
- Urinalysis
- Urine pH levels
- Blood pH levels
- Urine calcium levels
- Urine citric acid levels
- Urine potassium levels
- Blood potassium levels
- Short ammonium chloride test or acid loading test
An alternative test that uses fludrocortisone and furosemide has been described more recently.
Renal Tubular Acidosis Differential Diagnosis
A number of health conditions resemble the signs and symptoms commonly shown by RTA. It is, thus, necessary for a doctor to differentiate RTA from these similar conditions while determining the clinical diagnosis so that appropriate treatment measures can be undertaken. The differential diagnoses of RTA include conditions like:
- Azotemia
- Lactic Acidosis
- Renal glycosuria
- Salicylate Toxicity
- Metabolic Alkalosis
- Acute Renal Failure
- Respiratory alkalosis
- Diabetic ketoacidosis
- Chronic Renal Failure
- Non-specific diarrhea
- Primary aminoacidurias
- Diabetes Mellitus, Types 1 and 2
Renal Tubular Acidosis Treatment
Distal RTA is treated with supplementations of oral sodium bicarbonate, potassium citrate or sodium citrate. This will help in correcting the symptoms of acidosis and bone demineralization. Nephrocalcinosis, hypokalemia and the urinary stone formations can be cured by using potassium citrate tablets. These oral medications not only help in replacing potassium but also hinder calcium excretion. Hence, they do not exacerbate the chances of stone diseases as sodium citrate or bicarbonate might do.
Proximal RTA is treated with oral bicarbonate supplementation. Unfortunately, this might increase urinary bicarbonate wastes and promote bicarbonate diuresis. Correction with oral bicarbonates might exacerbate loss of urinary potassium and precipitate hypokalemia. Reversal of chronic acidosis would reverse the symptoms of bone demineralization. Thiazide diuretics, which can cause contraction alkalosis, can also be used to treat proximal RTA.
Patients having the Type 4 RTA can be treated by alkaline agents that might help in correcting the symptoms of acidosis. Medications to lower the levels of blood potassium can be prescribed by a doctor.
Renal Tubular Acidosis Complications
RTA patients might suffer from the following complications:
- Rickets
- Osteomalacia
- Kidney stones
- Nephrocalcinosis
- Electrolyte imbalances, like Hypokalemia
Renal Tubular Acidosis Prognosis
The outcome for RTA is positive for most patients treated with appropriate medical care. However, a number of conditions associated with RTA might require separate treatment. Sometimes, permanent or life-threatening complications might develop in severe cases of RTA which may prove to be critical. Long term prognosis varies from one case to another, and cases of both full recovery and fatalistic implications have been recorded.