An overview of types 1, 2, and 4 is presented below (type 3 is exceedingly rare and is usually excluded from discussions of the disease):
Type 1: Distal Distal RTA (dRTA) is the classical form of RTA, being the first described. Distal RTA is characterized by a failure of H+ secretion into lumen of nephron by the alpha intercalated
cells of the
medullary collecting duct of the
distal nephron. This failure of acid secretion may be due to a number of causes, and it leads to an inability to acidify the urine to a
pH of less than 5.3. Because renal excretion is the primary means of eliminating from the body, there is consequently a tendency towards
acidemia. There is an inability to excrete H+ while cannot be reclaimed by the cell, leading to acidemia (as builds up in the body) and hypokalemia (as cannot be reabsorbed by the alpha cell). This leads to the clinical features of dRTA; •
Nephrocalcinosis (deposition of
calcium in the substance of the kidney) •
Bone demineralisation (causing
rickets in children and
osteomalacia in adults) • Growth deficiency •
Medullary cysts •
Sensorineural hearing loss •
Hereditary hemolytic anemia Distal RTA has also been linked to specific genetic mutations that will alter when the disease will present in the patient's life. Patient's with mutations in
ATP6V1B1 and
ATP6V0A4 will present with symptoms within the first year of life, while those with mutation of the
SLC4A1 have delayed onset around 10 years of age. Electrolyte imbalances remain the same, while in severe cases symptoms can advance to
amino aciduria and
hyperammonemia. In a large Asian series of Distal renal Tubular Acidosis in Sjogren's Syndrome, late diagnosis is a rule in spite of overt hypokalemic periodic paralysis in a vast majority of them dRTA is the most common form of RTA diagnosed in Western countries, and can be classified as either hereditary (primary) or acquired (secondary). Primary RTA generally results from systemic and autoimmune diseases or drug and toxin exposure in adults, whereas pediatric RTA results from genetic defects in the proteins that facilitate urine acidification at the distal tubule. Hereditary dRTA generally presents as failure to thrive during the first several months of life. Other common clinical manifestations in children include a variety of gastrointestinal and urinary symptoms, including polyuria, polydipsia, constipation, diarrhea, bouts of dehydration, and decreased appetite.
Type 2: Proximal of a child with
rickets, a complication of both proximal and, less commonly, distal RTA. Proximal RTA (pRTA) is caused by a failure of the
proximal tubular cells to reabsorb filtered bicarbonate from the urine, leading to urinary
bicarbonate wasting and subsequent
acidemia. Reabsorption of bicarbonate is typically 80-90% in the proximal tubule and failure of this process leads to decreased systemic buffer and
metabolic acidosis. This failure may be
idiopathic, with an unclear cause and no associated clinical syndrome, or it may be secondary to any of several known syndromes, notably
Wilson's Disease. pRTA also has several causes, and may occasionally be present as a solitary defect, but is usually associated with a more generalized dysfunction of the proximal tubular cells called
Fanconi syndrome, in which there is also
phosphaturia,
glycosuria, aminoaciduria, uricosuria, and tubular
proteinuria. The principal feature of Fanconi syndrome is often bone demineralization (
osteomalacia or
rickets) due to phosphate wasting.
Type 3: Combined proximal and distal In some patients, RTA shares features of both dRTA and pRTA. This rare pattern was observed in the 1960s and 1970s as a transient phenomenon in infants and children with dRTA (possibly in relation with some exogenous factor such as high salt intake) and is no longer observed. This form of RTA has also been referred to as juvenile RTA. Combined dRTA and pRTA is also observed as the result of inherited
carbonic anhydrase II deficiency. Mutations in the gene encoding this enzyme give rise to an autosomal recessive syndrome of
osteopetrosis, renal tubular acidosis,
cerebral calcification, and intellectual disability. It is very rare and cases from all over the world have been reported, of which about 70% are from the
Maghreb region of North Africa, possibly due to the high prevalence of
consanguinity there. The kidney problems are treated as described above. There is no treatment for the osteopetrosis or cerebral calcification. Type 3 is rarely discussed. Most comparisons of RTA are limited to a comparison of types 1, 2, and 4.
Type 4: Absolute hypoaldosteronism or aldosterone insensitivity , or to a resistance to its effects. Type 4 RTA is not actually a tubular disorder at all nor does it have a clinical syndrome similar to the other types of RTA described above. It was included in the classification of renal tubular acidoses as it is associated with a mild (normal anion gap) metabolic acidosis due to a
physiological reduction in proximal tubular
ammonium excretion (impaired ammoniagenesis), which is secondary to
hypoaldosteronism, and results in a decrease in urine buffering capacity. Its cardinal feature is
hyperkalemia, and measured urinary acidification is normal, hence it is often called hyperkalemic RTA or tubular hyperkalemia. Causes include: • Aldosterone deficiency (
hypoaldosteronism): Primary vs. hyporeninemic (including diabetic nephropathy) •
Aldosterone resistance • Drugs:
NSAIDs,
ACE inhibitors and
ARBs,
Eplerenone,
Spironolactone,
Trimethoprim,
Pentamidine •
Pseudohypoaldosteronism ==History==